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While numerous methods exist for diagnosing tumors through the detection of miRNA within tumor cells, few can simultaneously achieve both tumor diagnosis and treatment. In this study, a novel graphene oxide (GO)-based DNA nanodevice (DND), initiated by miRNA, was developed for fluorescence signal amplification imaging and photodynamic therapy in tumor cells. After entering the cells, tumor-associated miRNA drives DND to Catalyzed hairpin self-assembly (CHA). The CHA reaction generated a multitude of DNA Y-type structures, resulting in a substantial amplification of Ce6 fluorescence release and the generation of numerous singlet oxygen (1O2) species induced by laser irradiation, consequently inducing cell apoptosis. In solution, DND exhibited high selectivity and sensitivity to miRNA-21, with a detection limit of 11.47 pM. Furthermore, DND discriminated between normal and tumor cells via fluorescence imaging and specifically generated O21 species in tumor cells upon laser irradiation, resulting in tumor cells apoptosis. The DND offer a new approach for the early diagnosis and timely treatment of malignant tumors.

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INTRODUCTION: This study clarified the expression changes and clinical significance of CD44+CD62L- Treg and CD44-CD62L+ Treg subsets in the peripheral blood of patients with allergic rhinitis (AR). METHODS: The peripheral blood of 39 patients with AR and 42 healthy controls was collected. Clinical data, such as sex, age, IgE titer, allergen screening information and visual analogue scale (VAS) score, were recorded. Changes in serum IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ were detected using the cytometric bead array method. Flow cytometry was used to detect the proportions of Th1, Th2, Th17, TFH, and Th9 cells and the proportions of CD44+CD62L- Treg and CD44-CD62L+ Treg subsets. Correlation analysis was performed between the CD44+CD62L- Treg subsets and the CD44-CD62L+ Treg subsets with clinical indicators (VAS score, total IgE titer), cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ), and Th1/Th2/Th17/TFH/Th9 cell proportions. RESULTS: Compared to the control group, the proportion of total Treg cells and CD44+CD62L- Treg cells in the AR group decreased, and the proportion of CD44-CD62L+ Treg cells increased (p < 0.05). The proportions of CD44+CD62L- Treg cells significantly negatively correlated with Th2 cells (R = -0.5270, p < 0.05) and positively correlated with Treg cytokine IL-10 (R = 0.6447, p < 0.05). In addition, CD44+CD62L- Treg cells negatively correlated with the VAS score (R = -0.4956, p < 0.05), total IgE level (R = -0.4177, p < 0.05) and Th2 cytokine IL-6 level (R = -0.3034, p < 0.05) but positively correlated with the Th1 cytokine IL-2 (R = 0.4331, p < 0.05). In contrast, the proportion of CD44+CD62L- Treg cells significantly positively correlated with the Th2 cells (R = 0.6187, p < 0.05). Moreover, the proportion of CD44-CD62L+ Treg cells positively correlated with the VAS score (R = 0.4060, p < 0.05), total IgE level (R = 0.5224, p < 0.05) and Th2 cytokine IL-4 (R = 0.2647, p < 0.05) and IL-6 levels (R = 0.3824, p < 0.05) but negatively correlated with Th1 cytokine IL-2 (R = -0.3451, p < 0.05) and IL-10 (R = -0.3277, p < 0.05). CONCLUSION: A greater proportion of CD44+CD62L- Tregs correlated with better reversal of the Th1/Th2 imbalance and milder clinical symptoms in AR patients. The presence of more CD44-CD62L+ Tregs correlated with a weaker immunosuppressive effect on Th2 cells and more severe clinical symptoms in AR patients. These findings provide new perspectives for the treatment and disease monitoring of AR.

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OBJECTIVES: Endoscopic necrosectomy (EN) is a promising minimally invasive approach for treating infected walled-off pancreatic necrosis (WOPN). Multiple EN approaches are currently available, though criteria for selecting the optimal approaches are lacking. We aimed to propose a rational selection strategy of EN and to retrospectively evaluate its safety and effectiveness. METHODS: Altogether 101 patients who underwent EN for infected WOPN at a tertiary hospital between June 2009 and February 2023 were retrospectively included for analysis. Demographic characteristics, details of the EN procedures, procedure-related adverse events, and clinical outcomes were investigated. RESULTS: Among these 101 patients with WOPN, 56 (55.4%) underwent transluminal EN, 38 (37.6%) underwent percutaneous EN, and seven (6.9%) underwent combined approach, respectively. Clinical success was achieved in 94 (93.1%) patients. Seven (6.9%) experienced procedure-related adverse events, and seven (6.9%) died during the treatment period. During a median follow-up of 50 months, 5 (5.3%) of the 94 patients had disease recurrence, 17.0% (16/94) had new-onset diabetes mellitus, and 6.4% (6/94) needed oral pancreatic enzyme supplementation. The clinical success rate, procedure-related adverse event rate, and long-term follow-up outcomes were not significantly different among the three groups. High APACHE-II scores (≥15) and organ failure were identified as factors related to treatment failure. CONCLUSIONS: A selection strategy for EN approaches, based on the extent of necrosis and its distance from the gastrointestinal lumen (using a threshold of 15 mm), is safe and effective for treating infected WOPN in both short-term and long-term outcomes.

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The non-trivial magnetic and electronic phases occurring in topological magnets are often entangled, thus leading to a variety of exotic physical properties. Recently, the BaAl4-type compounds have been extensively investigated to elucidate the topological features appearing in their real- and momentum spaces. In particular, the topological Hall effect and the spin textures, typical of the centrosymmetric Eu(Al,Ga)4family, have stimulated extensive experimental and theoretical research. In this topical review, we discuss the latest findings regarding the Eu(Al,Ga)4topological antiferromagnets and related materials, arising from a vast array of experimental techniques. We show that Eu(Al,Ga)4represents a suitable platform to explore the interplay between lattice-, charge-, and spin degrees of freedom, and associated emergent phenomena. Finally, we address some key questions open to future investigation.

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BACKGROUND: Home parenteral nutrition (HPN) can improve the nutritional status of patients with gastrointestinal dysfunction. However, some patients face a series of challenges during its implementation, which significantly affect their quality of life. AIMS: To explore the experience and needs of living with home parenteral nutrition in adult patients. DESIGN: A systematic review and meta-synthesis. METHODS: A search was conducted across multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, Chinese Biomedical Literature Service System, China National Knowledge Infrastructure, Wanfang Database and Wipu Database, to explore the real-life experiences and needs of adult patients receiving HPN. The search covered the period up to March 2024. Qualitative research quality was evaluated using the Joanna Briggs Institute's Australian Centre for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research. Data synthesis was performed using Thomas and Harden's method of thematic and content analysis. RESULTS: Twelve studies, each offering qualitative data, were analysed, resulting in the identification of four themes: positive experiences of HPN; the interplay of dynamic changes across physical, mental and social levels; self-adjustment to the new normal; and multidimensional needs of patients receiving HPN. CONCLUSIONS: Patients receiving HPN face multiple challenges physically, psychologically and socially. This paper also reveals the supportive needs of patients in adapting to a new lifestyle with HPN. This indicates that healthcare professionals should provide comprehensive, continuous and dynamic supportive medical services to facilitate patients' reintegration and return to normal social life. PATIENT AND PUBLIC INVOLVEMENT: As this study constitutes a meta-synthesis, patient or public contribution is not applicable. REPORTING APPROACH: Adhering to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) reporting guidelines, this meta-synthesis was conducted.

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Unlike traditional drug carriers, sequential drug delivery systems can release different drugs in order, with the first released drug providing a prerequisite for the later released drug to maximize its function, thereby achieving stronger anti-tumor effects. Herein we constructed a temporal sequential system designated TPZ@MSN/HIF-1α siRNA@PDA@GOx (MTRPG) in which mesoporous silica nanoparticles were used as cores to load hypoxia induced chemotherapy drug tirapazamine (TPZ) and gene targeted nucleic acid drug HIF-1α siRNA, polydopamine (PDA) as acid -responsive coating as well as to realize photothermal therapy, and glucose oxidase (GOx) as the outermost layer to achieve starvation therapy and construct a deepened hypoxia to activate TPZ. Through in vitro and in vivo experiments, we demonstrated that the first released glucose oxidase catalyzed the oxidation of glucose, achieving starvation treatment while reducing the acidic environment and further exacerbating hypoxia in tumor cells. The reduced acidic conditions enabled the degradation of PDA, resulting in the release of loaded HIF-1α siRNA and TPZ. At the same time, PDA could also exert photothermal therapy under 808 nm near-infrared (808 nm NIR) laser irradiation. The later released hypoxia induced chemotherapy drug TPZ amplifies its anti-tumor activity under intensified hypoxia conditions. Meanwhile, the released HIF-1α siRNA interfered with the up-regulated HIF-1α induced by the deepened hypoxia condition, which caused hypoxia tolerance in tumors, reduced its expression activity, and achieved synergistic killing of tumor cells with chemotherapy. This work provides an effective multimodal synergistic therapy strategy to promote tumor therapeutic index, which may possess a promising future in clinical application.

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BACKGROUND: Many studies have demonstrated the effectiveness of chimeric antigen receptor-T (CAR-T) cell therapy for relapsed or refractory multiple myeloma (RRMM), but the hematologic toxicity has not been well characterized. METHODS: A total of 111 adults with RRMM who received BCMA CAR-T cells, BCMA + CD19 CAR-T cells or tandem BCMA/CD19 dual-target (BC19) CAR-T cells infusion were enrolled. We characterized cytopenia and hematologic recovery at different time points after CAR-T-cell therapy, analyzed the effect of cytopenia on prognosis and identified the risk factors. RESULTS: Patients had a high probability of cytopenia, with anemia, neutropenia and thrombocytopenia occurring in 92%, 95% and 73%, respectively. There were 60 (54%) patients had prolonged hematologic toxicity (PHT) after D28. The median hemoglobin and platelet count were significantly lower at D28 post-CAR-T cell therapy than at baseline. Hemoglobin increased to above baseline at D90. The median absolute neutrophil count was lower than baseline at D0 and D28, and it recovered to baseline at D180. The baseline level of lactate dehydrogenase was associated with thrombocytopenia. Extramedullary involvement was associated with hemoglobin recovery, while the baseline level of albumin and types of CAR-T were related to platelet recovery. Patients with anemia at baseline and at D0, D180 and D360 had shorter progression-free survival (PFS), while anemia at D0, D60, D180 and D360 was associated with shorter overall survival (OS). Neutropenia at D0 was associated with shorter PFS and patients with neutropenia at D90 or D180 had shorter OS. Patients with thrombocytopenia at any time had shorter PFS and OS. Compared to patients without PHT, patients with PHT had shorter PFS and OS. CONCLUSIONS: The majority of RRMM patients treated with CAR-T cells experienced cytopenia. Cytopenia occurred at specific time points was associated with a poorer prognosis.

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INTRODUCTION: To investigate the effects of different reading postures on intraocular pressure (IOP) and near-work-induced transient myopia (NITM) in children with myopia. METHODS: Sixty myopic children were instructed to read a book text placed at 33 cm for 30 min with two different reading postures: head bowed and head upright postures. The participants' IOP and NITM were assessed using a rebound tonometer and an open-field autorefractor. The measurement of IOP was conducted prior to reading, during reading sessions (at 5, 10, 20, and 30-min intervals), and after a 5-min recovery period. RESULTS: For the head bowed posture, the mean baseline IOP was 16.13 ± 2.47 mmHg. A significant rise in IOP was observed after 5 min of reading (17.17 ± 2.97 mmHg; +1.03 ± 2.29 mmHg; p = 0.014). Subsequent measurements revealed a further increase after 20 min (17.87 ± 2.90 mmHg; +1.73 ± 2.58 mmHg; p < 0.001), which continued to persist even after 30 min of reading (17.57 ± 3.46 mmHg; +1.43 ± 2.66 mmHg; p = 0.002). The IOP at different time points measured in the head upright posture did not show any significant difference in comparison to the baseline measurement (all p = 1.000). Compared to reading with the head upright, reading with the head bowed resulted in a greater increase in IOP at each time point (p < 0.05). Furthermore, the NITM was higher for reading with the head bowed than for reading with head upright at 30 min (-0.24 ± 0.53 D vs. -0.12 ± 0.47 D, p = 0.038). CONCLUSION: Reading in a head bowed position resulted in greater increases in IOP and NITM compared to reading in a head upright posture.

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The discovery of severe acute respiratory syndrome-coronavirus-2-like and Middle East respiratory syndrome-coronavirus-like viruses in Malayan pangolins has raised concerns about their potential role in the spread of zoonotic diseases. Herein, we describe the isolation and whole-genome sequencing of potentially zoonotic two bacterial pathogens from diseased Malaysian pangolins (Manis javanica)-Corynebacterium ulcerans and Erysipelothrix sp. The newly identified species were designated as C. ulcerans P69 and Erysipelothrix sp. P66. C. ulcerans P69 exhibited 99.2% whole-genome nucleotide identity to human bacterial isolate 4940, suggesting that it might have zoonotic potential. Notably, C. ulcerans P69 lacked the diphtheria toxin (tox) gene that is widely used in vaccines to protect humans from corynebacterial infection, which suggests that the current vaccine may be of limited efficacy against this pangolin strain. C. ulcerans P69 also contains other known virulence-associated genes such as pld and exhibits resistance to several antibiotics (erythromycin, clindamycin, penicillin G, gentamicin, tetracycline), which may affect its effective control. Erysipelothrix sp. P66 was closely related to Erysipelothrix sp. strain 2-related strains, exhibiting 98.8% whole-genome nucleotide identity. This bacterium is lethal in mice, and two commercial vaccines failed to protect its challenge, such that it could potentially pose a threat to the swine industry. Overall, this study highlights that, in addition to viruses, pangolins harbor bacteria that may pose a potential threat to humans and domestic animals, and which merit attention. IMPORTANCE: This study firstly reports the presence of two potentially zoonotic bacteria, Corynebacterium ulcerans and Erysipelothrix sp., in diseased Malaysian pangolins collected in 2019. The pangolin C. ulcerans is lethal in mice and resists many antibiotics. It clustered with a lethal human strain but lacked the diphtheria toxin gene. Diphtheria toxin is widely used as a vaccine around the world to protect humans from the infection of corynebacteria. The lack of the tox gene suggests that the current vaccine may be of limited efficacy against this pangolin strain. The pangolin Erysipelothrix sp. is the sister clade of Erysipelothrix rhusiopathiae. It is lethal in mice, and two commercial vaccines failed to protect the mice against challenge with the pangolin Erysipelothrix sp., such that this strain could potentially pose a threat to the swine industry. These findings emphasize the potential threat of pangolin bacteria.

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BACKGROUND: The most popular traditional Chinese exercise (TCE) techniques include Tai Chi, Yijinjing, Baduanjin, Wuqinxi, and Qigong. Exercise is advised as a primary treatment for knee osteoarthritis (KOA) according to clinical standards. According to several studies, TCE may be an effective way to help people with KOA manage their pain, stiffness, and physical function. Which TCE therapy is the most effective and whose particular usefulness is still debatable. The network meta-analysis (NMA) method is used in this study to evaluate and compare the effects of various TCE therapies on KOA patients. METHODS: We will search PubMed, Embase, Scopus, Cochrane Library, Web of Science, the China National Knowledge Infrastructure, Wanfang, the Chinese Scientific Journal Database (VIP), and the China Biology Medical Literature Database (CBM) for randomized controlled trials reporting TCE therapy for KOA patients published before October 25, 2023. The Stata 16.0 program will compare the effectiveness of various TCE therapies on KOA patients using conventional pairwise and NMA. RESULTS: The final 29 studies included 15 articles on Tai Chi, 7 articles on Baduanjin, 4 articles on Wuqinxi, and 3 articles on Yijinjing. Tai Chi was first for the effect sizes of VAS scores, WOMAC pain scores, and WOMAC available scores, while Baduanjin was ranked top for WOMAC stiffness scores. Research should continue to be conducted on the effect of Qigong on KOA intervention. CONCLUSIONS: This NMA will help determine the best TCE treatment for KOA and offer evidence-based bias for clinical decision-making.

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The phospholipase A2 (PLA2) superfamily has attracted increasing attention in recent years due to the multiple physiological and pathological functions exerted by its members. Up to date, the knowledge about the biological role of PLA2XIIA subfamily members remains limited. In this study, a new member of PLA2XIIA subfamily, LcPLA2XIIA, was characterized in large yellow croaker. Different from most members of the PLA2 superfamily with positive charge, LcPLA2XIIA encodes an anionic protein, which is similar to other members of PLA2XIIA subfamily. LcPLA2XIIA is highly expressed in the intestine, and afterwards, it is up-regulated after with Pseudomonas plecoglossicida or Staphylococcus aureus. LcPLA2XIIA exhibits strong inhibitory activity against these two bacteria. The results indicate that LcPLA2XIIA plays an important role in the antimicrobial immune responses of large yellow croaker. LcPLA2XIIA displays strong binding activity to all the tested bacteria. It specifically interacts with LTA, a unique component on the surface of Gram-positive bacteria. It also significantly promotes bacterial agglutination in the presence of Ca2+. These findings reveal that the binding and agglutinating abilities of LcPLA2XIIA to bacteria contribute greatly to its antibacterial activity. In addition, LcPLA2XIIA significantly inhibits the proliferation of infectious hematopoietic necrosis virus instead of recombinant human adenovirus type 5. It also suppresses the growth of human colorectal adenocarcinoma cells by inducing apoptosis, but it has no obvious inhibitory effect on the growth of epithelioma papulosum cyprinid cells. This study provides new insights into the antibacterial activity, and the mechanism of LcPLA2XIIA in large yellow croaker, and antiviral and antitumor functions of PLA2XIIA subfamily members.

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BACKGROUND: We aimed to evaluate the role of Contrast-enhanced intraoperative ultrasound (CE-IOUS) with perfluorobutane microbubbles (Sonazoid) in improving the prognosis of patients with unresectable colorectal cancer liver metastases (CRLM). METHODS: A total of 130 Patients with unresectable CRLM who underwent curative hepatic resection at our institute were retrospectively analyzed. Of these 130 enrolled patients, 67 underwent intraoperative ultrasound alone (IOUS group); 63 underwent additional CE-IOUS and IOUS (CE-IOUS group). Normalized inverse probability treatment weighting (IPTW) was employed to balance baseline characteristics between groups. Hepatic recurrence-free survival (HRFS) and overall survival (OS) were compared. RESULTS: The treatment strategy was altered in 25 patients (25/63, 39.9%) due to the additional use of CE-IOUS. After applying IPTW, the CE-IOUS group exhibited a significantly lower rate of hepatic recurrence (hazard ratio [HR], 0.55; 95% confidence interval [CI] 0.32-0.95; P = 0.032). Subgroup analysis showed that CE-IOUS provided a significant benefit over IOUS in patients with bilobar liver metastases (P = 0.007), or with a number of live tumors < 3 (P = 0.021), or without DLM (P = 0.018), or with extrahepatic metastasis (P = 0.034), or with a minimum of 6 cycles of systemic therapy (P = 0.03). CONCLUSIONS: CE-IOUS is necessary for unresectable CRLM after preoperative chemotherapy, as it enhances detection accuracy and improves the prognosis of unresectable CRLM patients.

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Gasdermin-mediated inflammatory cell death (pyroptosis) can activate protective immunity in immunologically cold tumors. Here, we performed a high-throughput screen for compounds that could activate gasdermin D (GSDMD), which is expressed widely in tumors. We identified 6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline (DMB) as a direct and selective GSDMD agonist that activates GSDMD pore formation and pyroptosis without cleaving GSDMD. In mouse tumor models, pulsed and low-level pyroptosis induced by DMB suppresses tumor growth without harming GSDMD-expressing immune cells. Protection is immune-mediated and abrogated in mice lacking lymphocytes. Vaccination with DMB-treated cancer cells protects mice from secondary tumor challenge, indicating that immunogenic cell death is induced. DMB treatment synergizes with anti-PD-1. DMB treatment does not alter circulating proinflammatory cytokine or leukocyte numbers or cause weight loss. Thus, our studies reveal a strategy that relies on a low level of tumor cell pyroptosis to induce antitumor immunity and raise the possibility of exploiting pyroptosis without causing overt toxicity.

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Cancer cells edit gene expression to evade immunosurveillance. However, genome-wide studies of gene editing during early tumorigenesis are lacking. Here we used single-cell RNA sequencing in a breast cancer genetically engineered mouse model (GEMM) to identify edited genes without bias. Late tumors repressed antitumor immunity genes, reducing infiltrating immune cells and tumor-immune cell communications. Innate immune genes, especially interferon-stimulated genes, dominated the list of downregulated tumor genes, while genes that regulate cell-intrinsic malignancy were mostly unedited. Naive and activated CD8+ T cells in early tumors were replaced with exhausted or precursor-exhausted cells in late tumors. Repression of immune genes was reversed by inhibiting DNA methylation using low-dose decitabine, which suppressed tumor growth and restored immune control, increasing the number, functionality and memory of tumor-infiltrating lymphocytes and reducing the number of myeloid suppressor cells. Decitabine induced important interferon, pyroptosis and necroptosis genes, inflammatory cell death and immune control in GEMM and implanted breast and melanoma tumors.

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BACKGROUND: To analyze the learning curve of novices in mastering short-term Spinal cord stimulation (st-SCS) for diabetic foot, evaluating the efficacy, safety, and difficulty of this technique. METHODS: A retrospective review of diabetic foot patients treated with st-SCS at our hospital was conducted. All procedures were performed by the same physician and patients were sequentially numbered according to the order of surgery. Learning curves were plotted using segmented linear regression and cumulative sum curves based on surgery duration. Patients were divided into 2 groups according to the inflection points on the learning curve: the learning group and the mastery group. Pre- and postoperative efficacy indicators were recorded and compared, along with general patient data, perioperative parameters, and incidence of complications. RESULTS: A total of 36 patients were included. Significant improvements were observed post-st-SCS in ulcer size (from 7.00 cm2 to 4.00 cm2), visual analog scale (from 7.00 to 3.00), foot temperature (from 30.06°C to 32.37°C), and Pittsburgh Sleep Quality Index (from 14.42 to 8.36) (P < 0.05). The physician could proficiently perform st-SCS after 9 cases. Surgery time was significantly shorter in the mastery group (1-9 cases) compared to the learning group (10-36 cases) (28.04 vs. 43.56 min, P < 0.05). There were no significant differences between the 2 groups in baseline data, improvement in efficacy indicators, or complications (P > 0.05). CONCLUSIONS: St-SCS is beneficial for wound healing, pain relief, improving peripheral circulation, and improving sleep quality. Surgeons can master this simple and safe technique in about 9 cases.

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Size-resolved gas-particle partitioning of semi-volatile organic compounds (SVOCs) can affect their environmental behaviors and health effects, which has not been widely studied in comparing with the gas-total suspended particle partitioning. Herein, the size-resolved gas-particle partitioning quotient (KPi) of polycyclic aromatic hydrocarbons (PAHs) in a large temperature range (-20.6 â„ƒ ∼ 29.4 â„ƒ) was firstly comprehensively studied. The log KPi values of PAHs related to fine particles were significantly higher than those related to coarse particles. When the logarithm of subcooled liquid-vapor pressure (log PL0) ∈ [-7, -1), the regression slopes of log KPi vs log PL0 related to the particle size > 1.0 µm were shallower than those with the particle size range of 0.10-1.0 µm, which indicated the influence of particle size on KPi. Among the three previous prediction equations of gas-particle partitioning quotient, the empirical equation based on the ambient temperature matched better with the measured log KPi. Therefore, a new prediction equation including ambient temperature and particle size as the two major parameters was established. For most particle size ranges, the new equation showed better prediction performance than the three previous equations. In summary, this study provided new insights for the size-resolved gas-particle partitioning mechanism and quotient.

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AIMS: To determine whether inflammatory biomarkers are causal risk factors for more myopic refractive errors. METHODS: Northern Sweden Population Health Study (NSPHS), providing inflammatory biomarkers data; UK Biobank, providing refractive errors data. 95,619 European men and women aged 40 to 69 years with available information of refractive errors and inflammatory biomakers. Inflammatory biomarkers including ADA, CCL23, CCL25, CD6, CD40, CDCP-1, CST5, CXCL-5, CXCL-6, CXCL-10, IL-10RB, IL-12B, IL-15RA, IL-18R1, MCP-2, MMP-1, TGF-ß1, TNF-ß, TWEAK and VEGF-A were exposures, and spherical equivalent (SE) using the formula SE = sphere + (cylinder/2) was outcome. RESULTS: Mendelian randomization analyses showed that each unit increase in VEGF-A, CD6, MCP-2 were causally related to a more myopic refractive errors of 0.040 D/pg.mL-1 (95% confidence interval 0.019 to 0.062; P = 2.031 × 10-4), 0.042 D/pg.mL-1 (0.027 to 0.057; P = 7.361 × 10-8) and 0.016 D/pg.mL-1 (0.004 to 0.028; P = 0.009), and each unit increase in TWEAK was causally related to a less myopic refractive errors of 0.104 D/pg.mL-1 (-0.152 to -0.055; P = 2.878 × 10-5). Tested by the MR-Egger, weighted median, MR-PRESSO, Leave-one-out methods, our results were robust to horizontal pleiotropy and heterogeneity in VEGF-A, MCP-2, CD6, but not in TWEAK. CONCLUSIONS: Our Mendelian Randomization analysis supported the causal effects of VEGF-A, MCP-2, CD6 and TWEAK on myopic refractive errors. These findings are important for providing new indicators for early intervention of myopia to make myopic eyesight threatening consequences less inevitable.

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The surface of three-dimensional materials provides an ideal and versatile platform to explore quantum-confined physics. Here, we systematically investigate the electronic structure of Na-intercalated CrTe2, a van der Waals antiferromagnet, using angle-resolved photoemission spectroscopy and ab initio calculations. The measured band structure deviates from the calculation of bulk NaCrTe2 but agrees with that of ferromagnetic monolayer CrTe2. Consistently, we observe unexpected exchange splitting of the band dispersions, persisting well above the Néel temperature of bulk NaCrTe2. We argue that NaCrTe2 features a quantum-confined 2D ferromagnetic state in the topmost surface layer due to strong ferromagnetic correlation in the CrTe2 layer. Moreover, the exchange splitting and the critical temperature can be controlled by surface doping of alkali-metal atoms, suggesting the feasibility of tuning the surface ferromagnetism. Our work not only presents a simple platform for exploring tunable 2D ferromagnetism but also provides important insights into the quantum-confined low-dimensional magnetic states.

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PAMP-triggered immunity (PTI) is the first layer of plant defense response that occurs on the plant plasma membrane. Recently, the application of a rhizobacterium, Bacillus amyloliquefaciens strain PMB05, has been demonstrated to enhance flg22Pst- or harpin-triggered PTI response such as callose deposition. This PTI intensification by PMB05 further contributes to plant disease resistance to different bacterial diseases. Under the demand for rapid and large-scale screening, it has become critical to establish a non-staining technology to identify microbial strains that can enhance PTI responses. Firstly, we confirmed that the expression of the GSL5 gene, which is required for callose synthesis, can be enhanced by PMB05 during PTI activation triggered by flg22 or PopW (a harpin from Ralstonia solanacearum). The promoter region of the GSL5 gene was further cloned and fused to the coding sequence of gfp. The constructed fragments were used to generate transgenic Arabidopsis plants through a plant transformation vector. The transgenic lines of AtGSL5-GFP were obtained. The analysis was performed by infiltrating flg22Pst or PopW in one homozygous line, and the results exhibited that the green fluorescent signals were observed until after 8 h. In addition, the PopW-induced fluorescent signal was significantly enhanced in the co-treatment with PMB05 at 4 h after inoculation. Furthermore, by using AtGSL5-GFP to analyze 13 Bacillus spp. strains, the regulation of PopW-induced fluorescent signal was observed. And, the regulation of these fluorescent signals was similar to that performed by callose staining. More importantly, the Bacillus strains that enhance PopW-induced fluorescent signals would be more effective in reducing the occurrence of bacterial wilt. Taken together, the technique by using AtGSL5-GFP would be a promising platform to screen plant immunity-intensifying microbes to control bacterial wilt.

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Relapsed/refractory multiple myeloma patients with extramedullary disease (EMD) have unfavorable prognosis and lack effective therapy. Chimeric antigen receptor (CAR) T-cell activities in EMD have yet to be determined; how EMD-specific microenvironment influences the clinical outcomes of CAR T-cell therapy remains of great interest. In this prospective cohort study, patients with histologically confirmed extra-osseous EMD were enrolled and treated with combined anti-BCMA and anti-CD19 CAR T-cell therapy from May 2017 to September 2023. Thirty-one patients were included in the study. Overall response occurred in 90.3% of medullary disease and 64.5% of EMD (p = .031). Discrepancies in treatment response were noted between medullary and extramedullary diseases, with EMD exhibiting suboptimal and delayed response, as well as shortened response duration. With a median follow-up of 25.3 months, the median progression-free and overall survival were 5.0 and 9.7 months, respectively. Landmark analysis demonstrated that progression within 6 months post-infusion is strongly associated with an increased risk of death (HR = 4.58; p = .029). Compared with non-EMD patients, patients with EMD showed inferior survival outcomes. Unique CAR-associated local toxicities at EMD were seen in 22.6% patients and correlated with the occurrence and severity of systemic cytokine release syndrome. To the cutoff date, 65% treated patients experienced EMD progression, primarily in the form of BCMA+ progression. The pretherapy EMD immunosuppressive microenvironment, characterized by infiltration of exhausted CD8+ T cells, was associated with inferior clinical outcomes. CAR T cells have therapeutic activity in relapsed/refractory EMD, but the long-term survival benefits may be limited. EMD-specific microenvironment potentially impacts treatment. Further efforts are needed to extend EMD remission and improve long-term outcomes.