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OBJECTIVE: To assess the feasibility of using non-mydriatic fundus photography in conjunction with an artificial intelligence (AI) reading platform for large-scale screening of diabetic retinopathy (DR). METHODS: In this study, we selected 120 patients with diabetes hospitalized in our institution from December 2019 to April 2021. Retinal imaging of 240 eyes was obtained using non-mydriatic fundus photography. The fundus images of these patients were divided into two groups based on different interpretation methods. In Experiment Group 1, the images were analyzed and graded for DR diagnosis using an AI reading platform. In Experiment Group 2, the images were analyzed and graded for DR diagnosis by an associate chief physician in ophthalmology, specializing in fundus diseases. Concurrently, all patients underwent the gold standard for DR diagnosis and grading-fundus fluorescein angiography (FFA)-with the outcomes serving as the Control Group. The diagnostic value of the two methods was assessed by comparing the results of Experiment Groups 1 and 2 with those of the Control Group. RESULTS: Keeping the control group (FFA results) as the gold standard, no significant differences were observed between the two experimental groups regarding diagnostic sensitivity, specificity, false positive rate, false negative rate, positive predictive value, negative predictive value, Youden's index, Kappa value, and diagnostic accuracy (X2 = 0.371, P > 0.05). CONCLUSION: Compared with the manual reading group, the AI reading group revealed no significant differences across all diagnostic indicators, exhibiting high sensitivity and specificity, as well as a relatively high positive predictive value. Additionally, it demonstrated a high level of diagnostic consistency with the gold standard. This technology holds potential for suitability in large-scale screening of DR.

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Taste and odor (T&O) are among the most frequently encountered aesthetic issues in drinking water. While fungi have been reported to produce offensive odors, their contribution to T&O in drinking water remains understudied and often overlooked. In this study, the profiles of fungal community and odorants produced by 10 native fungal isolates were investigated in 36 samples collected from two drinking water treatment plants and a premise plumbing system. A total of 17 odorants were identified with Penicillium, Aspergillus, Paecilomyces, and Alternaria genera exhibiting the highest odorant yields. Significant concentrations of musty/earthy compounds were produced by these fungal isolates, such as 2-methylisoborneol (2-MIB) (26-256 ng/L), geosmin (10-13 ng/L), and 2-isobutyl-3-methoxy-pyrazine (IBMP) (3-13 ng/L). The high odor activity value of the odorants primarily occurred within 4 d, while toxicity continued to increase during the 8 d incubation. UV treatment in premise plumbing significantly (p < 0.05) reduced the gene read counts of Ascomycota phylum, Aspergillus spp., Fusarium spp., Rhizopus spp., and Trichoderma spp., by 2.3-4.0 times. These findings underscore the previously underestimated role of fungi in contributing to T&O issues in drinking water and corresponding risks to consumers and indicate UV as a promising strategy for fungal control in drinking water.

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Background: Immune checkpoint inhibitors (ICIs) have greatly improved the survival in several cancers. Immune-related adverse events (irAEs) are common in patients on ICI therapy, as inhibition of cytotoxic T-lymphocyte antigen 4 (CTLA-4) or programmed cell death protein 1 (PD-1) leads to non-selective activation of the immune system. ICI-induced enterocolitis is highly prevalent and corticosteroid administration is the first-line treatment. Selective immunosuppressive therapy was employed for steroid-refractory patients. The monoclonal antibody vedolizumab exhibits gut-specific immunosuppressive effects by targeting the α4ß7 integrin. Case Description: We report a case of corticosteroid-dependent camrelizumab-induced enterocolitis in a 58-year-old man with hepatocellular carcinoma (HCC) who was treated with vedolizumab. The patient's diarrhea resolved following the administration of two doses of vedolizumab (300 mg), and he was able to stop using corticosteroids. He later underwent surgery and HCC treatment, including appropriate management of ICI-induced enterocolitis, and achieved a complete pathological response. Conclusions: This report illustrates the valuable role of vedolizumab in treating ICI-induced enterocolitis that is refractory to corticosteroid treatment.

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Objective: To evaluate whether improved progression-free survival (PFS) from radiotherapy (RT) translates into an overall survival (OS) benefit for diffuse large B-cell lymphoma (DLBCL). Methods: A systematic literature search identified randomized controlled trials (RCTs) and retrospective studies that compared combined-modality therapy (CMT) with chemotherapy (CT) alone. Weighted regression analyses were used to estimate the correlation between OS and PFS benefits. Cohen's kappa statistic assessed the consistency between DLBCL risk-models and PFS patterns. Furthermore, the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio (HR) according to the PFS patterns. Results: For both 7 RCTs and 52 retrospective studies, correlations were found between PFS HR (HRPFS) and OS HR (HROS) at trial level (r = 0.639-0.876), and between PFS and OS rates at treatment-arm level, regardless of CT regimens (r = 0.882-0.964). Incorporating RT into CT increased about 18% of PFS, and revealed a different OS benefit profile. Patients were stratified into four CT-generated PFS patterns (>80%, >60-80%, >40-60%, and ≤40%), which was consistent with risk-stratified subgroups (kappa > 0.6). Absolute gain in OS from RT ranged from ≤5% at PFS >80% to about 21% at PFS ≤40%, with pooled HROS from 0.70 (95% CI, 0.51-0.97) to 0.48 (95% CI, 0.36-0.63) after rituximab-based CT. The OS benefit of RT was predominant in intermediate- and high-risk patients with PFS ≤ 80%. Conclusion: We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.

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BACKGROUND: Depression is common and phenotypically heterogenous in multiple sclerosis (MS). MS may increase risk of some but not all affective symptoms or certain symptoms may predispose individuals to higher MS risk. OBJECTIVE: To assess the existence and direction of causality between distinct depressive symptoms and MS using two-sample Mendelian randomization (MR). METHODS: Using summary data from genome-wide association studies, we selected genetic instrument variables (IV) for MS (n = 115,776) and IVs for depressive symptoms (average n = 117,713): anhedonia, altered appetite, concentration, depressed mood, fatigue, inadequacy, psychomotor changes, sleeping problems and suicidality. We performed two-sample MR in either direction using inverse-variance models. Sensitivity analyses included weighted-median and MR-Egger regression. Obesity is a known risk factor for MS and depression; we adjusted for body mass index in multivariable-MR. RESULTS: Genetic liability to MS was associated with anhedonia (IVW estimate per 102: 0.69; 95 % CI: 0.24-1.13; p = 0.002), concentration difficulty (0.66; 0.19-1.13; p = 0.006) and psychomotor changes (0.37; 0.08-0.65; p = 0.01). Results were similar in sensitivity analyses. In the opposite direction, we found no evidence of a causal relationship for any affective symptom on MS risk. CONCLUSIONS: Genetic susceptibility to MS was associated with anhedonia, concentration, and psychomotor-related symptoms, suggesting a specific phenotype of depression in MS.

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Monolignol serves as the building blocks to constitute lignin, the second abundant polymer on Earth. Despite two decades of diligent efforts, complete identification of all metabolites in the currently proposed monolignol biosynthesis pathway has proven elusive. This limitation also hampers their potential application. One of the primary obstacles is the challenge of assembling a collection of all molecules, because many are commercially unavailable or prohibitively costly. In this study, we established systematic pipelines to synthesize all 24 molecules through the conversions between functional groups on a core structure followed by the application to other core structures. We successfully identified all of them in Populus trichocarpa and Eucalyptus grandis, two representative species respectively from malpighiales and myrtales in angiosperms. Knowledge about monolignol metabolite chemosynthesis and identification will form the foundation for future studies.

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Unconventional 1T' phase transition metal dichalcogenides (TMDs) show great potential for hydrogen evolution reaction (HER). However, they are susceptible to transitioning into the stable 2H phase, which reduces their catalytic activity and stability. Herein, we present a scalable approach for designing thermally stable 1T'-TMDs hollow structures (HSs) by etching Cu1.94S templates from pre-synthesized Cu1.94S@TMDs heterostructures, including 1T'-MoS2, MoSe2, WS2, and WSe2 HSs. Furthermore, taking 1T'-MoS2 HSs as an example, the etched Cu ions can be firmly adsorbed on their surface in the form of single atoms (SAs) through Cu-S bonds, thereby elevating the phase transition temperature from 149 ºC to 373 ºC. Due to the advantages conferred by the 1T' phase, hollow structure, and synergistic effect between Cu SAs and 1T'-MoS2 supports, the fabricated 1T'-MoS2 HSs demonstrate superior HER performance. Notably, their high-phase stability enables continuous operation of designed 1T'-MoS2 HSs for up to 200 hours at an ampere-level current density without significant activity decay. This work provides a universal method for synthesizing highly stable 1T'-TMDs electrocatalysts, with a particular focus on the relationship between their phase and catalytic stability.

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Excessive fibrotic scar formation during skin defect repair poses a formidable challenge, impeding the simultaneous acceleration of wound healing and prevention of scar formation and hindering the restoration of skin integrity and functionality. Drawing inspiration from the structural, compositional, and biological attributes of skin, we developed a hydrogel containing modified recombinant human collagen type III and thiolated hyaluronic acid to address the challenges of regenerating skin appendages and improving the recovery of skin functions after injury by reducing fibrotic scarring. The hydrogel displayed favorable biocompatibility, antioxidant properties, angiogenic potential, and fibroblast migration stimulation in vitro. In a rat full-layer defect model, it reduced inflammation, promoted microvascular formation, and significantly enhanced the wound healing speed and effectiveness. Additionally, by upregulating fibrosis-associated genes, such as TGFB1, it facilitated collagen accumulation and a beneficial balance between type I and type III collagen, potentially expediting skin regeneration and functional recovery. In conclusion, the utilization of rhCol III-HS demonstrated considerable potential as a wound dressing, offering a highly effective strategy for the restoration and rejuvenation of complete skin defects.

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BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) remains a significant challenge in cancer therapy, especially due to its resistance to established treatments like Gemcitabine, necessitating novel therapeutic approaches. METHODS: This study utilized Gemcitabine-resistant cell lines, patient-derived organotypic tumor spheroids (PDOTs), and patient-derived xenografts (PDX) to evaluate the effects of Saikosaponin-a (SSA) on ICC cellular proliferation, migration, apoptosis, and its potential synergistic interaction with Gemcitabine. Techniques such as transcriptome sequencing, Luciferase reporter assays, and molecular docking were employed to unravel the molecular mechanisms. RESULTS: SSA exhibited antitumor effects in both in vitro and PDX models, indicating its considerable potential for ICC treatment. SSA markedly inhibited ICC progression by reducing cellular proliferation, enhancing apoptosis, and decreasing migration and invasion. Crucially, it augmented Gemcitabine's efficacy by targeting the p-AKT/BCL6/ABCA1 signaling pathway. This modulation led to the downregulation of p-AKT and suppression of BCL6 transcriptional activity, ultimately reducing ABCA1 expression and enhancing chemosensitivity to Gemcitabine. Additionally, ABCA1 was validated as a predictive biomarker for drug resistance, with a direct correlation between ABCA1 expression levels and the IC50 values of various small molecule drugs in ICC gene profiles. CONCLUSION: This study highlights the synergistic potential of SSA combined with Gemcitabine in enhancing therapeutic efficacy against ICC and identifies ABCA1 as a key biomarker for drug responsiveness. Furthermore, the introduction of the novel PDOTs microfluidic model provides enhanced insights into ICC research. This combination strategy may provide a novel approach to overcoming treatment challenges in ICC.

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Transportador 1 de Casete de Unión a ATP , Neoplasias de los Conductos Biliares , Colangiocarcinoma , Desoxicitidina , Resistencia a Antineoplásicos , Gemcitabina , Ácido Oleanólico , Proteínas Proto-Oncogénicas c-akt , Saponinas , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Ácido Oleanólico/farmacología , Ácido Oleanólico/análogos & derivados , Saponinas/farmacología , Colangiocarcinoma/tratamiento farmacológico , Humanos , Línea Celular Tumoral , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Transportador 1 de Casete de Unión a ATP/metabolismo , Ratones , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Sinergismo Farmacológico , Ensayos Antitumor por Modelo de Xenoinjerto

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INTRODUCTION: The estimated dose of radiation to immune cells (EDRIC) has been shown to correlate with the overall survival (OS) of patients who receive definitive thoracic radiotherapy. However, the planning target volume (PTV) may be a confounding factor. We assessed the prognostic value of EDRIC for non-small cell lung cancer (NSCLC) in patients who underwent postoperative radiotherapy (PORT) with homogeneous PTV. METHODS: Patients with NSCLC who underwent PORT between 2004 and 2019 were included. EDRIC was computed as a function of the number of radiation fractions and mean doses to the lungs, heart, and remaining body. The correlations between EDRIC and OS, disease-free survival (DFS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed using univariate and multivariate Cox models. Kaplan-Meier analysis was performed to assess the survival difference between low- and high-EDRIC groups. RESULTS: In total, 345 patients were analyzed. The mean EDRIC was 6.26 Gy. Multivariate analysis showed that higher EDRIC was associated with worse outcomes in terms of OS (hazard ratio [HR] 1.207, P = .007), DFS (HR 1.129, P = .015), LRFS (HR 1.211, P = .002), and DMFS (HR 1.131, P = .057). In the low- and high-EDRIC groups, the 3-year OS was 81.2% and 74.0%, DFS 39.8% and 35.0%, LRFS 70.4% and 60.5%, and DMFS 73.9% and 63.1%, respectively. CONCLUSIONS: EDRIC is an independent prognostic factor for survival in patients with NSCLC undergoing PORT. Higher doses of radiation to the immune system are associated with tumor progression and poor survival. Organs at risk for the immune system should be considered during radiotherapy planning.

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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Masculino , Femenino , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/inmunología , Persona de Mediana Edad , Anciano , Pronóstico , Estudios Retrospectivos , Dosificación Radioterapéutica , Adulto , Anciano de 80 o más Años , Estimación de Kaplan-Meier , Supervivencia sin Enfermedad , Radioterapia Adyuvante

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Calcination of MgCO3 is an important industrial reaction, but it causes significant and unfavorable CO2 production. Calcination in a reducing green hydrogen atmosphere can substantially reduce CO2 release and produce high value-added products such as CO or hydrocarbons, but the mechanism is still unclear. Here, the in situ transformation process of MgCO3 interacting with hydrogen and the specific formation mechanism of the high value-added products are thoroughly investigated based on reaction thermodynamic, ab initio molecular dynamics (AIMD) simulations, and density functional theory (DFT) calculations. The reaction thermodynamic parameters of MgCO3 coupled with hydrogen to produce CO or methane are calculated, revealing that increasing and decreasing the thermal reductive decomposition temperature favors the production of CO and methane, respectively. Kinetically, the energy barriers of each possible production pathway for the dominant products CO and methane are further calculated in conjunction with the AIMD simulation results of the transformation process. The results suggest that CO is produced via the MgO catalytic-carboxyl pathway (CO2*→ COOH*trans→ COOH*cis→ CO*→ CO), which is autocatalyzed by MgO derived from the thermal reductive decomposition of MgCO3. For the mechanism of methane formation, it prefers to be produced by the stepwise interaction of carbonates in the MgCO3 laminates with hydrogen adsorbed on their surfaces (direct conversion pathway: sur-O-CO → sur-O-HCO → sur-O-HCOH → sur-O-HC → sur-O-CH2 → sur-O-CH3 → sur-O + CH4*).

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The mechanisms underlying tissue repair in response to damage have been one of main subjects of investigation. Here we leverage the wound-induced hair neogenesis (WIHN) models in adult mice to explore the correlation between degree of damage and the healing process and outcome. The multimodal analysis, in combination with single-cell RNA sequencing help to explore the difference in wounds of gentle and heavy damage degrees, identifying the potential role of toll-like receptor 9 (TLR9) in sensing the injury and regulating the immune reaction by promoting the migration of γδT cells. The TLR9 deficient mice or wounds injected with TLR9 antagonist have greatly impaired healing and lower WIHN levels. Inhibiting the migration of γδT cells or knockout of γδT cells also suppress the wound healing and regeneration, which can't be rescued by TLR9agonist. Finally, the amphiregulin (AREG) is shown as one of most important effectors secreted by γδT cells and keratinocytes both in silicon or in the laboratory, whose expression influences WIHN levels and the expression of stem cell markers. In total, our findings reveal a previously unrecognized role for TLR9 in sensing skin injury and influencing the tissue repair and regeneration by modulation of the migration of γδT cells, and identify the TLR9-γδT cells-areg axis as new potential targets for enhancing tissue regeneration.

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Folículo Piloso , Regeneración , Receptor Toll-Like 9 , Cicatrización de Heridas , Animales , Folículo Piloso/metabolismo , Receptor Toll-Like 9/metabolismo , Receptor Toll-Like 9/genética , Ratones , Ratones Endogámicos C57BL , Anfirregulina/metabolismo , Anfirregulina/genética , Movimiento Celular , Ratones Noqueados , Queratinocitos/metabolismo , Linfocitos Intraepiteliales/metabolismo

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We present a nonlinear spectroelectrochemical technique to investigate photosynthetic protein complexes. The PEC2DES setup combines photoelectrochemical detection (PEC) that selectively probes the protein photogenerated charges output with two-dimensional electronic spectroscopy (2DES) excitation that spreads the nonlinear optical response of the system in an excitation-detection map. PEC allows us to distinguish the contribution of charge separation (CS) from other de-excitation pathways, whereas 2DES allows us to disentangle congested spectral bands and evaluate the exciton dynamics (decays and coherences) of the photosystem complex. We have developed in operando phase-modulated 2DES by measuring the photoelectrochemical reaction rate in a biohybrid electrode functionalized with a plant photosystem complex I-light harvesting complex I (PSI-LHCI) layer. Optimizing the photoelectrochemical current signal yields reliable linear spectra unequivocally associated with PSI-LHCI. The 2DES signal is validated by nonlinear features like the characteristic vibrational coherence at 750 cm-1. However, no energy transfer dynamics is observed within the 450 fs experimental window. These intriguing results are discussed in the context of incoherent mixing resulting in reduced nonlinear contrast for multichromophoric complexes, such as the 160 chlorophyll PSI. The presented PEC2DES method identifies generated charges unlike purely optical 2DES and opens the way to probe the CS channel in multichromophoric complexes.

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BACKGROUND: Bleomycin, originally an antitumor drug, was explored as a pathological scar treatment in the mid-1990s. However, its efficacy and safety profile varies among individuals. AIMS: This study aimed to assess topical bleomycin's efficacy and safety in treating hypertrophic scars and keloids. METHODS: We reviewed randomized controlled trials (RCTs) and controlled clinical trials (CCTs) published in English, comparing intralesional bleomycin to placebos or common intralesional scar treatments. Primary outcomes included percentage change in scar improvement, pigmentation, recurrence, atrophy, pain, telangiectasia, ulceration, patient self-assessment, and observer assessment (>50%). RESULTS: Six trials met the criteria. Bleomycin significantly improved scar reduction compared to triamcinolone (p < 0.05). There was no significant difference in pigmentation (p = 0.05) and recurrence (p = 0.21) compared to other treatments. In terms of safety, bleomycin caused less skin atrophy (p < 0.01) and telangiectasia (p < 0.01) but more pain (p = 0.03) than other treatments. CONCLUSIONS: Bleomycin was more effective than TAC, 5-FU, or TAC combined with 5-FU for treating keloids and hypertrophic scars with lower skin atrophy and telangiectasia risks. However, it may cause more pain than 5-FU or TAC. Further comprehensive studies, including RCTs, are required for objective analysis.

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Sub-aperture polishing is a key technique for fabricating ultra-precision optics. However, the existence of the polishing errors that are difficult to be compensated by physical modeling seriously affects the manufacturing accuracy and efficiency of optical components. To address this problem, a data-based systematic error extraction and compensation (DSEC) method was proposed to enhance the polishing accuracy on optics. To maximize the extraction quality in a small dataset condition, the wavelet transform is introduced into the extraction process, and the uncertainty of the piston term in the interferometer measurement is improved by L1-norm optimization. Furthermore, two typical error sources (loss of polishing fluid in the edge and the robot trajectory error) are used to verify the effectiveness of the proposed method; in experimental verification, the root mean square (RMS) of the surface figure of a ϕ85-mm mirror was decreased from 0.069λ to 0.017λ, and the RMS of the 610 × 440 mm mirrors was achieved at 0.019λ after the edge compensation, where the polishing accuracy can be improved by more than 4 times; additionally, the RMS of the surface figure with an effective aperture of 480 × 360 mm mirror was reached at 0.011λ after the trajectory error compensation, where the polishing accuracy can be improved by more than 2 times. The proposed DSEC model offers insights that will help achieve advancement in the sub-aperture polishing process.

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The aetiology of bone metastasis in prostate cancer (PCa) remains unclear. This study aims to identify hub genes involved in this process. We utilized machine learning, GO, KEGG, GSEA, Single-cell analysis, ROC methods to identify hub genes for bone metastasis in PCa using the TCGA and GEO databases. Potential drugs targeting these genes were identified. We validated these results using 16 specimens from patients with PCa and analysed the relationship between the hub genes and clinical features. The impact of APOC1 on PCa was assessed through in vitro experiments. Seven hub genes with AUC values of 0.727-0.926 were identified. APOC1, CFH, NUSAP1 and LGALS1 were highly expressed in bone metastasis tissues, while NR4A2, ADRB2 and ZNF331 exhibited an opposite trend. Immunohistochemistry further confirmed these results. The oxidative phosphorylation pathway was significantly enriched by the identified genes. Aflatoxin B1, benzo(a)pyrene, cyclosporine were identified as potential drugs. APOC1 expression was correlated with clinical features of PCa metastasis. Silencing APOC1 significantly inhibited PCa cell proliferation, clonality, and migration in vitro. This study identified 7 hub genes that potentially facilitate bone metastasis in PCa through mitochondrial metabolic reprogramming. APOC1 emerged as a promising therapeutic target and prognostic marker for PCa with bone metastasis.

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Neoplasias Óseas , Proliferación Celular , Biología Computacional , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Próstata , Humanos , Neoplasias Óseas/secundario , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Biología Computacional/métodos , Proliferación Celular/genética , Línea Celular Tumoral , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Movimiento Celular/genética , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Pronóstico

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Objective: To investigate the prevalence of subthreshold depression among Chinese college students and to explore the related factors. Methods: The research subjects were Chinese college students participating in the "2022 Psychology and Behavior Investigation of Chinese Residents (PBICR-2022)". Data on respondents' general characteristics, quality of life, perceived pressure, family communication, perceived social support, self-efficacy, and depression status were gathered. To investigate the association between each variable and the risk of subthreshold depression, statistical analyses, including chi-square tests and rank sum tests were conducted. Furthermore, a binary stepwise logistic regression was employed to establish the regression model of the factors related to subthreshold depression among Chinese college students. Results: A prevalence of subthreshold depression of about 39.7 % was found among the 8934 respondents. Logistic regression analysis revealed that respondents who are female, have chronic diseases, are in debt, experience significant impacts from epidemic control policies, have lower self-assessed quality of life, experience challenges in family communication, perceive lower social support, have lower self-efficacy, and feel higher perceived pressure are more likely to develop subthreshold depression compared to the control group. (P < 0.05). Conclusion: The prevalence rate of subthreshold depression among Chinese college students was found to be approximately 40 %. Female college students suffering from chronic diseases, with households in debt, greatly impacted by epidemic control policies, and experiencing high perceived stress, may be at risk for subthreshold depression among Chinese college students. On the other hand, strong family communication, perceived social support, and self-efficacy were identified as potential protective factors. In order to facilitate timely screening, diagnosis, and treatment of subthreshold depression in Chinese college students, it is crucial for the government, local communities, colleges, and families to prioritize the mental health of college students and implement targeted measures accordingly.

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AIM: For patients with locally advanced rectal cancer, previous STELLAR studies have shown that a new adjuvant treatment paradigm of short-course radiotherapy followed by neoadjuvant chemotherapy can achieve pathological complete response rates superior to those of standard care; however, the 3-year DFS is inferior to neoadjuvant concurrent radiotherapy. Recent studies have shown that immune checkpoint inhibitors may improve the prognosis of rectal cancer and have good synergy with radiotherapy. Therefore, neoadjuvant chemotherapy combined with immune checkpoint inhibitors after a short course of radiotherapy has the potential to further improve complete response rates and prognosis. METHOD: The STELLAR II study is a multicentre, open label, two-arm randomized, phase II/III trial of short-course radiotherapy followed by neoadjuvant chemotherapy concurrent with immunotherapy for locally advanced rectal cancer. A total of 588 patients with locally advanced rectal cancer (LARC) will be randomly assigned to the experimental and control groups. The experimental group will receive short-course radiotherapy and neoadjuvant chemotherapy in combination with sindilizumab, while the control group will receive short-course radiotherapy and neoadjuvant chemotherapy. Both groups will subsequently receive either total rectal mesenteric resection or a watch & wait (W&W) strategy. The phase II primary endpoint is the complete remission rate, and the secondary endpoints include grade 3-4 adverse events, perioperative complications, R0 resection rate, overall survival, local recurrence rate, distant metastasis rate and quality of life score. A seamless phase II/III randomized controlled design will be used to investigate the effectiveness and safety of the TNT strategy with the addition of immunotherapy. The trial opened, and the first patient was recruited on 31 August 2022. Trial registration number and date of registration: ClinicalTrials.gov NCT05484024, 29 July 2022. DISCUSSION: The STELLAR II trial will prospectively evaluate the efficacy of TNT treatment strategies that incorporate immune checkpoint inhibitors. The trial will yield important information to guide routine management of patients with local advanced rectal cancer.

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Using sewage (wastewater) for ocean alkalinity enhancement (OAE) has been considered as one promising ocean negative carbon emissions (ONCE) approach due to its high carbon sequestration efficiency and low environmental risk. To make this process more profitable and sustainable, this perspective proposes to integrate bicarbonate-based microalgal production and sewage alkalinity enhancement for ONCE. In this concept, the spent aqueous alkaline bicarbonate-based microalgal medium is cheap or even free for OAE, while the produced microalgae with high value-added compositions make this process more profitable. To make the proposed idea more efficient and sustainable, the prospects for its future development are also discussed in this opinion article. This perspective provides a novel and practical idea for achieving efficient carbon neutralization and high economic value simultaneously.

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Obesity-induced chronic inflammation exacerbates multiple types of tissue/organ deterioration and stem cell dysfunction; however, the effects on skeletal tissue and the underlying mechanisms are still unclear. Here, we show that obesity triggers changes in the microRNA profile of macrophage-secreted extracellular vesicles, leading to a switch in skeletal stem/progenitor cell (SSPC) differentiation between osteoblasts and adipocytes and bone deterioration. Bone marrow macrophage (BMM)-secreted extracellular vesicles (BMM-EVs) from obese mice induced bone deterioration (decreased bone volume, bone microstructural deterioration, and increased adipocyte numbers) when administered to lean mice. Conversely, BMM-EVs from lean mice rejuvenated bone deterioration in obese recipients. We further screened the differentially expressed microRNAs in obese BMM-EVs and found that among the candidates, miR-140 (with the function of promoting adipogenesis) and miR-378a (with the function of enhancing osteogenesis) coordinately determine SSPC fate of osteogenic and adipogenic differentiation by targeting the Pparα-Abca1 axis. BMM miR-140 conditional knockout mice showed resistance to obesity-induced bone deterioration, while miR-140 overexpression in SSPCs led to low bone mass and marrow adiposity in lean mice. BMM miR-378a conditional depletion in mice led to obesity-like bone deterioration. More importantly, we used an SSPC-specific targeting aptamer to precisely deliver miR-378a-3p-overloaded BMM-EVs to SSPCs via an aptamer-engineered extracellular vesicle delivery system, and this approach rescued bone deterioration in obese mice. Thus, our study reveals the critical role of BMMs in mediating obesity-induced bone deterioration by transporting selective extracellular-vesicle microRNAs into SSPCs and controlling SSPC fate.