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An immunoassay method based on penicillin-binding protein (PBP) was developed for the quantitative determination of 10 kinds of beta-lactam antibiotics (BLAs). First, two kinds of PBPs, which are named PBP1a and PBP2x, were expressed and purified, and they were characterized by SDS-PAGE and western blotting analysis. Then, the binding activity of PBP1a and PBP2x to template BLAs, cefquinome (CEFQ) and ampicillin (AMP), was determined. The effect of the buffer solution system, e.g., pH, ion concentration, and organic solvent, on the immune interaction efficiency between PBPs and BLAs was also evaluated. In the end, the PBP-based immunoassay method was developed and validated for the detection of 10 kinds of BLAs. Under optimal conditions, PBPs exhibited high binding affinity to BLAs. In addition, this method showed a high sensitivity for the detection of 10 kinds of BLAs with the limits of detection from 0.21 to 9.12 ng/mL, which are much lower than their corresponding maximum residual limit of European Union (4-100 ng/mL). Moreover, the developed PBP-immunoassay was employed for BLA detection from milk samples, and satisfactory recoveries (68.9-101.3 %) were obtained.

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Interleukin-33 (IL-33) is a member of the interleukin-1 cytokine family. Its function in regulating microglial M1/M2 polarization in neuromyelitis optica spectrum disorder (NMOSD) is still unelucidated. To evaluate the role of IL-33 in NMOSD, we constructed NMOSD mice model by injecting purified serum IgG from AQP4-IgG seropositive NMOSD patients into experimental autoimmune encephalomyelitis (EAE) mice, and IL-33 was intraperitoneally injected into NMOSD mice 3 d before the model induction. We found that pretreatment of the NMOSD mice with IL-33 relieved brain neuron loss, and demyelination and improved the structure of axons, astrocytes, and mitochondria. In the neuronal and microglial coculture system, pretreatment with IL-33 in microglia alleviated NMOSD serum-induced inflammation and damaged morphology in cultured neurons. IL-33 transformed microglia to the M2 phenotype, and NMOSD serum promoted microglia to the M1 phenotype in cultured BV2 cells. Moreover, IL-33 influenced microglial polarity via the IL-33/ST2 pathway. IL-33 may be a novel insight useful for further developing NMOSD-targeted therapy and drug development.

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The looming stimulus-evoked flight response to approaching predators is a defensive behavior in most animals. However, how looming stimuli are detected in the retina and transmitted to the brain remains unclear. Here, we report that a group of GABAergic retinal ganglion cells (RGCs) projecting to the superior colliculus (SC) transmit looming signals from the retina to the brain, mediating the looming-evoked flight behavior by releasing GABA. GAD2-Cre and vGAT-Cre transgenic mice were used in combination with Cre-activated anterograde or retrograde tracer viruses to map the inputs to specific GABAergic RGC circuits. Optogenetic technology was used to assess the function of SC-projecting GABAergic RGCs (scpgRGCs) in the SC. FDIO-DTA (Flp-dependent Double-Floxed Inverted Open reading frame-Diphtheria toxin) combined with the FLP (Florfenicol, Lincomycin & Prednisolone) approach was used to ablate or silence scpgRGCs. In the mouse retina, GABAergic RGCs project to different brain areas, including the SC. ScpgRGCs are monosynaptically connected to parvalbumin-positive SC neurons known to be required for the looming-evoked flight response. Optogenetic activation of scpgRGCs triggers GABA-mediated inhibition in SC neurons. Ablation or silencing of scpgRGCs compromises looming-evoked flight responses without affecting image-forming functions. Our study reveals that scpgRGCs control the looming-evoked flight response by regulating SC neurons via GABA, providing novel insight into the regulation of innate defensive behaviors.

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In clinical practice, we found cerebrospinal fluid magnesium concentration significantly lower in neuromyelitis optica spectrum disorder (NMOSD) patients compared to controls with non-autoimmune encephalitis neurological diseases. To investigate the effects and potential mechanisms of long-term magnesium supplementation on neuroinflammation, demyelination, and blood-brain barrier (BBB) integrity in NMOSD, we used two models: (1) NMOSD mouse model, which was induced by intraperitoneal injection of purified NMO-IgG to experimental autoimmune encephalomyelitis (EAE) mice, and (2) cultured human cerebral microvascular endothelial cells/D3 (hCMEC/D3). In the NMOSD mouse model, Magnesium L-threonate (MgT) pretreatment alleviated NMO-IgG-induced effects, including AQP4 loss, leukocyte infiltration, astrocyte and microglia activation, demyelination, decreased tight junction (TJ) protein expression, and neurological deficits. In vitro, MgT pretreatment ameliorated NMO-IgG induced damage to TJ protein expression in a (transient receptor potential melastatin 7) TRPM7-dependent manner. Magnesium supplementation shows potential protective effects against NMOSD, suggesting it may be a novel therapeutic approach for this condition. The beneficial effects appear to be mediated through preservation of blood-brain barrier integrity and reduction of neuroinflammation and demyelination.

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Fermented soybeans are popular among many for their rich soy sauce-like aroma. However, the precise composition of this aroma remains elusive, with key aroma compounds unidentified. In this study, we screened the candidate genes ilvA and serA in BJ3-2 based on previous multi-omics data, and we constructed three mutant strains, BJ3-2-ΔserA, BJ3-2-ΔilvA, and BJ3-2-ΔserAΔilvA, using homologous recombination to fermented soybeans with varying intensities of soy sauce-like aroma. Our objective was to analyze samples that exhibited different aroma intensities resulting from the fermented soybeans of BJ3-2 and its mutant strains, thereby exploring the key flavor compounds influencing soy sauce-like aroma as well analyzing the effects of ilvA and serA on soy sauce-like aroma. We employed quantitative descriptive sensory analysis (QDA), gas chromatography-olfactometry-mass spectrometry (GC-O-MS), relative odor activity value analysis (rOAV), principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), and partial least squares regression analysis (PLSR). QDA revealed the predominant soy sauce-like aroma profile of roasted and smoky aromas. GC-MS detected 99 volatile components, predominantly pyrazines and ketones, across the four samples, each showing varying concentrations. Based on rOAV (>1) and GC-O, 12 compounds emerged as primary contributors to soy sauce-like aroma. PCA and OPLS-DA were instrumental in discerning aroma differences among the samples, identifying five compounds with VIP > 1 as key marker compounds influencing soy sauce-like aroma intensity levels. Differential analyses of key aroma compounds indicated that the mutant strains of ilvA and serA affected soy sauce-like aroma mainly by affecting pyrazines. PLSR analysis indicated that roasted and smoky aromas were the two most important sensory attributes of soy sauce-like aroma, with pyrazines associated with roasted aroma and guaiacol associated with smoky aroma. In addition, substances positively correlated with the intensity of soy sauce-like aroma were verified by additional experiments. This study enhances our understanding of the characteristic flavor compounds in soy sauce-like aroma ferments, provides new perspectives for analyzing the molecular mechanisms of soy sauce-like aroma formation, and provides a theoretical framework for the targeted enhancement of soy sauce-like aroma in various foods.

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The chemical composition of dissolved organic matter (DOM) exerts significant influence on aquatic energy dynamics, pollutant transportation, and carbon storage, thereby playing pivotal roles in the local water quality and regional-global biogeochemical cycling. However, the effects of natural climate change and local human activities on watershed characteristics and in-river processes have led to uncertainties regarding their contributions to DOM chemistry in coastal rivers, creating challenges for effective water management and the study of organic matter cycling. In this investigation, we employed a combination of stable isotopic analysis, optical techniques, and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) to elucidate the sources, optical properties, and molecular composition of DOM in three South China coastal rivers. Our results suggest that terrestrial DOM entering the three rivers through natural or anthropogenic pathways is gradually diluted by in situ primary production as it moves downstream, ultimately being influenced by seawater intrusion near the estuary. Additionally, terrestrial processes influenced by temperature likely govern DOC concentration, while seawater intrusion promotes the natural production of S-containing organic compounds. In contrast, human-altered landcover significantly impacts DOM molecular composition. Increased water areas lead to the enrichment of lignins with high disinfection byproduct formation potential, and agricultural residue burning appears to be the dominant source of pyrogenic DOM in these coastal rivers. Our distinct results suggest that the development of specific water management plans that consider the combined effects of temperature, seawater intrusion, landcover changes, and agricultural practices will be essential to ensure sustainable water resource.

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Objective: This systematic review and meta-analysis aimed to investigate the association between circulating irisin levels and osteoporosis in women, exploring irisin's potential role in the pathophysiology and management of osteoporosis. Method: We searched PubMed, Embase, Web of Science, Cochrane Library, CNKI, WanFang, and VIP databases up to January 2023. The inclusion criteria were observational studies reporting on circulating irisin levels in women. The standardized mean difference (SMD) and correlation coefficients with a 95% confidence interval (CI) were used as the main effect measures under a random-effects model. Heterogeneity was evaluated using the Cochrane Q statistic and the I2 statistics. Subgroup analysis and univariate meta-regression analysis were performed to identify the sources of heterogeneity. The quality of the included study was assessed by the Newcastle-Ottawa Score. The quality of evidence was evaluated using the GRADE system. Publication bias was assessed using Begg's and Egger's test, and the trim-and-fill method. Sensitivity analysis was performed to assess the stability of the results. Results: Fifteen studies with a total of 2856 participants met the criteria. The analysis showed significantly lower irisin levels in postmenopausal osteoporotic women compared to non-osteoporotic controls (SMD = -1.66, 95% CI: -2.43 to -0.89, P < 0.0001; I2 = 98%, P < 0.00001) and in postmenopausal individuals with osteoporotic fractures than in non-fractures controls (SMD = -1.25, 95% CI: -2.15 to -0.34, P = 0.007; I2 = 97%, P < 0.00001). Correlation analysis revealed that irisin levels positively correlated with lumbar spine BMD (r = 0.37, 95% CI: 0.18 to 0.54), femoral BMD (r = 0.30, 95% CI: 0.18 to 0.42), and femoral neck BMD (r = 0.31, 95% CI: 0.14 to 0.47) in women. Despite significant heterogeneity, the robustness of the results was supported by using the random effects model and sensitivity analysis. Conclusion: The current evidence suggests that lower irisin levels are significantly associated with osteoporosis and fracture in postmenopausal women, suggesting its utility as a potential biomarker for early detection of osteoporosis and therapeutic target. However, further high-quality prospective research controlling for confounding factors is needed to clarify the relationship between irisin levels and osteoporotic outcomes. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023410264.

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Photodynamic therapy (PDT) is a promising and innovative approach for treating tumors. The synergistic effect of PDT and chemotherapy can enhance the anti-tumor efficacy by leveraging their complementing benefits. In this study, we created lipid vesicles to deliver a photosensitizer (chlorin e6, Ce6) and Regorafenib into tumors for the purpose of examining the effectiveness and mechanism of Lipo-Ce6@Rego-PDT (LCR-P) on Hepatocellular carcinoma (HCC) both in vitro and in vivo. We found that the cytotoxicity on HCC caused by LCR-P was significantly stronger than that caused by Lipo-Ce6-PDT (LC-P). Cellular ROS production in the LCR-P group was approximately higher than that in the LC-P group, and Regorafenib significantly inhibited the phosphorylation of JNK, ERK, and P38 of Lipo-Ce6-PDT group in vitro and in vivo. Furthermore, Regorafenib significantly downregulated the expression of Bcl-2 and upregulated the expression of Bax and cleaved caspase-3 of LC-P group in vitro and in vivo. Compared with LC-P, LCR-P significantly increased cell apoptosis rate. The body weight and HE staining of normal organs primarily indicated the safety of this combined strategy. These results indicate that the combination of Regorafenib and Lipo-Ce6 can significantly enhance the anti-tumor efficiency of PDT for HCC and exhibits good biosafety.

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The risk of Legionella transmission in built environments remains a significant concern. Legionella can spread within buildings through aerosol transmission, prompting the exploration of airborne transmission pathways and proposing corresponding prevention and control measures based on building characteristics. To this end, a comprehensive literature review on the transmission risk of Legionella in built environments was performed. Four electronic databases (PubMed, Web of Science, Google Scholar, and CNKI) were searched from inception to March 2024 for publications reporting the risk of Legionella transmission in built environments. Relevant articles and gray literature reports were hand-searched, and 96 studies were finally included. Legionella pollution comes from various sources, mainly originates in a variety of built environments in which human beings remain for extended periods. The sources, outbreaks, national standards, regulations, and monitoring techniques for Legionella in buildings are reviewed, in addition to increases in Legionella transmission risk due to poor maintenance of water systems and long-distance transmission events caused by aerosol characteristics. Air and water sampling using various analytical methods helps identify Legionella in the environment, recognize sources in the built environments, and control outbreaks. By comparing the standard regulations of national organizations globally, the authors further highlight gaps and deficiencies in Legionella surveillance in China. Such advancements offer essential insights and references for understanding and addressing Legionella transmission risk in the built environment, with the potential to contribute to safeguarding public health and building environment safety.

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Macrophages maintain surveillance of their environment using receptor-mediated endocytosis and pinocytosis. Receptor-mediated endocytosis allows macrophages to recognize and internalize specific ligands whereas macropinocytosis non-selectively internalizes extracellular fluids and solutes. Here, CRISPR/Cas9 whole-genome screens were used to identify genes regulating constitutive and growth factor-stimulated dextran uptake in murine bone-marrow derived macrophages (BMDM). The endocytic mannose receptor c-type 1 ( Mrc1 , also known as CD206) was a top hit in the screen. Targeted gene disruptions of Mrc1 reduced dextran uptake but had little effect on uptake of Lucifer yellow, a fluid-phase marker. Other screen hits also differentially affected the uptake of dextran and Lucifer yellow, indicating the solutes are internalized by different mechanisms. We further deduced that BMDMs take up dextran via MRC1-mediated endocytosis by showing that competition with mannan, a ligand of MRC1, as well as treatment with Dyngo-4a, a dynamin inhibitor, reduced dextran uptake. Finally, we observed that IL4-treated BMDM internalize more dextran than untreated BMDM by upregulating MRC1 expression. These results demonstrate that dextran is not an effective marker for the bulk uptake of fluids and solutes by macropinocytosis since it is internalized by both macropinocytosis and receptor-mediated endocytosis in cells expressing MRC1. This report identifies numerous genes that regulate dextran internalization in primary murine macrophages and predicts cellular pathways and processes regulating MRC1. This work lays the groundwork for identifying specific genes and regulatory networks that regulate MRC1 expression and MRC1-mediated endocytosis in macrophages. Significance Statement: Macrophages constantly survey and clear tissues by specifically and non-specifically internalizing debris and solutes. However, the molecular mechanisms and modes of regulation of these endocytic and macropinocytic processes are not well understood. Here, CRISPR/Cas9 whole genome screens were used to identify genes regulating uptake of dextran, a sugar polymer that is frequently used as a marker macropinocytosis, and compared with Lucifer yellow, a fluorescent dye with no known receptors. The authors identified the mannose receptor as well as other proteins regulating expression of the mannose receptor as top hits in the screen. Targeted disruption of Mrc1 , the gene that encodes mannose receptor, greatly diminished dextran uptake but had no effect on cellular uptake of Lucifer yellow. Furthermore, exposure to the cytokine IL4 upregulated mannose receptor expression on the cell surface and increased uptake of dextran with little effect on Lucifer yellow uptake. Studies seeking to understand regulation of macropinocytosis in macrophages will be confounded by the use of dextran as a fluid-phase marker. MRC1 is a marker of alternatively activated/anti-inflammatory macrophages and is a potential target for delivery of therapeutics to macrophages. This work provides the basis for mechanistic underpinning of how MRC1 contributes to the receptor-mediated uptake of carbohydrates and glycoproteins from the tissue milieu and distinguishes genes regulating receptor-mediated endocytosis from those regulating the bona fide fluid-phase uptake of fluids and solutes by macropinocytosis.

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Carbon superstructures with exquisite morphologies and functionalities show appealing prospects in energy realms, but the systematic tailoring of their microstructures remains a perplexing topic. Here, hydrangea-shaped heterodiatomic carbon superstructures (CHS) are designed using a solution phase manufacturing route, wherein machine learning workflow is applied to screen precursor-matched solvent for optimizing solvent-precursor interaction. Based on the established solubility parameter model and molecular growth kinetics simulation, ethanol as the optimal solvent stimulates thermodynamic solubilization and growth of polymeric intermediates to evoke CHS. Featured with surface-active motifs and consecutive charge transfer paths, CHS allows high accessibility of zincophilic sites and fast ion migration with low energy barriers. A anion-cation hybrid charge storage mechanism of CHS cathode is disclosed, which entails physical alternate uptake of Zn2+/CF3SO3 - ions at electroactive sites and chemical bipedal redox of Zn2+ ions with carbonyl/pyridine motifs. Such a beneficial electrochemistry contributes to all-round improvement in Zn-ion storage, involving excellent capacities (231 mAh g-1 at 0.5 A g-1; 132 mAh g-1 at 50 A g-1), high energy density (152 Wh kg-1), and long-lasting cyclability (100 000 cycles). This work expands the design versatilities of superstructure materials and will accelerate experimental procedures during carbon manufacturing through machine learning in the future.

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We report, to the best of our knowledge, the first demonstration of an O + E-band tunable watt-level bismuth-doped phosphosilicate fiber laser and its frequency doubling to tunable red laser. Benefiting from the two types of bismuth active centers associated with silicon and phosphorus introduced in one fiber, an ultrabroad gain is available in the designed low-water-peak bismuth-doped phosphosilicate fiber (Bi-PSF) pumped by a self-made 1239 nm Raman fiber laser. The high-efficiency tunable lasing is achieved with a maximum output power of 1.705 W around 1320 nm and a slope efficiency of 33.0%. The wavelength can be continuously tuned from 1283 to 1460 nm over a 177 nm spectral range, almost covering the whole O+E-bands. We further employ a polarization beam splitter in the cavity to output an O + E-band linear-polarization laser for second-harmonic generation by a designed multi-period MgO2:PPLN crystal, and a 650-690-nm tunable visible laser is correspondingly obtained. Such an O+E-wideband tunable high-power laser and the SHG red laser may have great potential in the all-band optical communications, biophotonics, and spectroscopy.

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Objective: To analyze the clinical and laboratory characteristics and to identify predictors of moderate to severe anti-tuberculosis drug-induced liver injury (ATB-DILI) in patients with tuberculosis. Methods: This prospective study enrolled Tuberculosis (TB) patients treated with first-line anti-tuberculosis drugs at the Affiliated Hospital of Zunyi Medical University between May 2022 and June 2023. The occurrence of ATB-DILI was monitored, and demographic and clinical data were gathered. We analyzed risk factors for the development of moderate to severe ATB-DILI. Results: ATB-DILI was detected in 120 (10.7%) of the patients, with moderate to severe ATB-DILI occurring in 23 (2.0%) of the 1,124 patients treated with anti-tuberculosis treatment. Multivariate cox regression analysis identified malnutrition (HR = 4.564, 95% CI: 1.029-20.251, p = 0.046) and hemoglobin levels <120 g/L (HR = 2.825, 95% CI: 1.268-11.540, p = 0.017) as independent risk factors for moderate to severe ATB-DILI. Conclusion: The incidence of moderate to severe ATB-DILI was found to be 2.0%. Malnutrition and hemoglobin levels below 120 g/L emerged as significant independent risk factors for the occurrence of moderate to severe ATB-DILI in this patient population.

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BACKGROUND: Sirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients. METHODS: This pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded. RESULTS: Sirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217). CONCLUSIONS: Sirolimus's long-term administration is not associated with adverse effects on children's physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration. TRIAL REGISTRATION: Pediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892.

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Objective: In this study, we collected perioperative and postoperative follow-up data from patients with endometrial cancer (EC) at different stages to evaluate the role of sentinel lymph node biopsy (SLNB) in endometrial cancer surgery. Methods: A total of 186 endometrial cancer patients undergoing radical hysterectomy from January 2018 to April 2022 were retrospectively analyzed. Patients were classified into four groups. Group A comprised patients diagnosed with stage IA grade 1 and 2 endometrioid EC who underwent SLNB. Group B comprised patients with stage IA grade 1 and 2 endometrioid EC who did not undergo SLNB. Group C comprised patients with higher-grade endometrioid EC, wherein systematic lymph node dissection was performed based on SLNB results. Group D comprised patients with higher-grade endometrioid EC who did not undergo SLNB and instead underwent direct systematic lymph node dissection. Clinical, pathological data, and follow-up information for all patients were collected. Results: In Group A and B, SLNB was performed on 36 out of 67 patients with IA stage 1 and 2 endometrial cancer, yielding a SLN positivity rate of 5.6%. There were no significant differences observed between the two groups regarding perioperative outcomes and postoperative follow-up. Conversely, among 119 patients with higher-grade endometrial cancer, 52 underwent SLNB, with 20 patients exhibiting SLN positivity, resulting in a SLN positivity rate of 38.4%. However, the decision to undergo SLNB did not yield significant differences in perioperative outcomes and postoperative follow-up among these patients. Conclusion: For stage IA grade 1 and 2 endometrioid EC, the incidence of lymph node positivity is low, omitting SLNB in this subpopulation is a feasible option. In other stages of endometrioid EC, there is no significant difference in perioperative and postoperative follow-up data between patients undergoing routine systematic lymphadenectomy and those undergoing systematic lymphadenectomy based on SLNB results. Therefore, if SLNB is not available, the standard procedure of PLND remains an option to obtain information about lymph node status, despite the surgical complications associated with this procedure.

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The mechanism governing sulfur cycling in nitrate reduction within sulfate-rich reservoirs during seasonal hypoxic conditions remains poorly understood. This study employs nitrogen and oxygen isotope fractionation in nitrate, along with metagenomic sequencing to elucidate the intricacies of the coupled sulfur oxidation and nitrate reduction process in the water column. In the Aha reservoir, a typical seasonally stratified water body, we observed the coexistence of denitrification, bacterial sulfide oxidation, and bacterial sulfate reduction in hypoxic conditions. This is substantiated by the presence of abundant N/S-related genes (nosZ and aprAB/dsrAB) and fluctuations in N/S species. The lower 15εNO3/18εNO3 ratio (0.60) observed in this study, compared to heterotrophic denitrification, strongly supports the occurrence of sulfur-driven denitrification. Furthermore, we found a robust positive correlation between the metabolic potential of bacterial sulfide oxidation and denitrification (p < 0.05), emphasizing the role of sulfide produced via sulfate reduction in enhancing denitrification. Sulfide-driven denitrification relied on ∑S2- as the primary electron donor preferentially oxidized by denitrification. The pivotal genus, Sulfuritalea, emerged as a central player in both denitrification and sulfide oxidation processes in hypoxic water bodies. Our study provides compelling evidence that sulfides assume a critical role in regulating denitrification in hypoxic water within an ecosystem where their contribution to the overall nitrogen cycle was previously underestimated.

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In spite of the increasing popularity of project-based collaborative learning (PBCL) as a pedagogy, real successful collaboration cannot always be achieved due to the cognitive, motivational and social emotional challenges students encounter during collaboration. Recognizing the challenges and developing regulation strategies to cope with the challenges at both individual and group level is essential for successful collaboration. In the last decades, a growing interest has been developed around socially shared regulation of emotions and how it is interwoven with self-regulation and co-regulation. However, capturing the process of students' emotional challenges and regulations in a long and dynamic project proves difficult and there remains a paucity of evidence on how co-regulation and socially-shared regulation co-occur with learners' cognitive and emotional progress in project-based collaborative learning. The purpose of the present study is to investigate and identify what kind of social emotional challenges students encountered during PBCL and how they regulate themselves and the groups in order to finish the projects. A quasi-experimental research design was adopted in an academic English classroom, with thirty-eight students self-reporting their challenges and regulations three times after finishing each of the projects. The results of qualitative analysis plus a case study of two groups indicate that students encounter a variety of social emotional challenges and employed different levels of co-regulation and socially shared regulation in addition to self-regulation, leading to varying collaboration results and experiences. The findings of the study offer insights into the emotional regulation in PBCL and shed light for future design of pedagogical interventions aiming at supporting socially shared regulation.

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OBJECTIVE: Most cases of hepatocellular carcinoma (HCC) arise as a consequence of cirrhosis. In this study, our objective is to construct a comprehensive diagnostic model that investigates the diagnostic markers distinguishing between cirrhosis and HCC. METHODS: Based on multiple GEO datasets containing cirrhosis and HCC samples, we used lasso regression, random forest (RF)-recursive feature elimination (RFE) and receiver operator characteristic analysis to screen for characteristic genes. Subsequently, we integrated these genes into a multivariable logistic regression model and validated the linear prediction scores in both training and validation cohorts. The ssGSEA algorithm was used to estimate the fraction of infiltrating immune cells in the samples. Finally, molecular typing for patients with cirrhosis was performed using the CCP algorithm. RESULTS: The study identified 137 differentially expressed genes (DEGs) and selected five significant genes (CXCL14, CAP2, FCN2, CCBE1 and UBE2C) to construct a diagnostic model. In both the training and validation cohorts, the model exhibited an area under the curve (AUC) greater than 0.9 and a kappa value of approximately 0.9. Additionally, the calibration curve demonstrated excellent concordance between observed and predicted incidence rates. Comparatively, HCC displayed overall downregulation of infiltrating immune cells compared to cirrhosis. Notably, CCBE1 showed strong correlations with the tumour immune microenvironment as well as genes associated with cell death and cellular ageing processes. Furthermore, cirrhosis subtypes with high linear predictive scores were enriched in multiple cancer-related pathways. CONCLUSION: In conclusion, we successfully identified diagnostic markers distinguishing between cirrhosis and hepatocellular carcinoma and developed a novel diagnostic model for discriminating the two conditions. CCBE1 might exert a pivotal role in regulating the tumour microenvironment, cell death and senescence.

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Allyl-ß-CD was synthesized and used as the chiral functional monomer to prepare chiral organic polymer monolithic columns in capillary HPLC. First, the enantioselectivity of the prepared allyl-ß-CD modified organic polymer monolithic capillary columns was investigated. Then, the influences of enantioseparation conditions of chiral drugs were further explored. Finally, the recognition mechanism was studied by molecular docking with AutoDock. Complete enantioseparations of four chiral drugs as well as partial enantioseparations of eight chiral drugs have been achieved. Results showed that the RSD values for run-to-run, day-to-day, and column-to-column variations ranged from 1.2% to 4.6%, 1.4% to 4.7%, and 2.0% to 6.1%, respectively. The enantioselectivity factor rather than resolution is correlated with the binding free energy difference between enantiomers with allyl-ß-CD. Furthermore, the abundant ether bonds, hydroxyl groups, and hydrophobic cavities in cyclodextrin are responsible for the enantioseparation ability of the chiral monolithic capillary columns.

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Biological nitrogen fixation catalyzed by nitrogenase contributes greatly to the global nitrogen cycle. Nitrogenase expression is subject to regulation in response to nitrogen availability. However, the mechanism through which the transcriptional activator NifA regulates nitrogenase expression by interacting with PII nitrogen regulatory proteins remains unclear in diazotrophic proteobacteria lacking NifL. Here, we demonstrate that in Rhodopseudomonas palustris grown with ammonium, NifA bound deuridylylated PII proteins to form an inactive NifA-PII complex, thereby inhibiting the expression of nitrogenase. Upon nitrogen limitation, the dissociation of uridylylated PII proteins from NifA resulted in the full restoration of NifA activity, and, simultaneously, uridylylation of the significantly up-regulated PII protein GlnK2 led to the increased expression of NifA in R. palustris. This insight into how NifA interacts with PII proteins and controls nitrogenase expression sets the stage for creating highly efficient diazotrophs, reducing the need for energy-intensive chemical fertilizers and helping to diminish carbon emissions.

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