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High-performance proton exchange membranes are of great importance for fuel cells. Here, we have synthesized polycarboxylate plasticizer modified MIL-101-Cr-NH2 (PCP-MCN), a kind of hybrid metal−organic framework, which exhibits a superior proton conductivity. PCP-MCN nanoparticles are used as additives to fabricate PCP-MCN/Nafion composite membranes. Microstructures and characteristics of PCP-MCN and these membranes have been extensively investigated. Significant enhancement in proton conduction for PCP-MCN around 55 °C is interestingly found due to the thermal motion of the PCP molecular chains. Robust mechanical properties and higher thermal decomposition temperature of the composite membranes are directly ascribed to strong intermolecular interactions between PCP-MCN and Nafion side chains, i.e., the formation of substantial acid–base pairs (-SO3−···+H–NH-), which further improves compatibility between additive and Nafion matrix. At the same humidity and temperature condition, the water uptake of composite membranes significantly increases due to the incorporation of porous additives with abundant functional groups and thus less crystallinity degree in comparison to pristine Nafion. Proton conductivity (σ) over wide ranges of humidities (30 − 100% RH at 25 °C) and temperatures (30 − 98 °C at 100% RH) for prepared membranes is measured. The σ in PCP-MCN/Nafion composite membranes is remarkably enhanced, i.e. 0.245 S/cm for PCP-MCN-3wt.%/Nafion is twice that of Nafion membrane at 98 °C and 100% RH, because of the establishment of well-interconnected proton transport ionic water channels and perhaps faster protonation–deprotonation processes. The composite membranes possess weak humidity-dependence of proton transport and higher water uptake due to excellent water retention ability of PCP-MCN. In particular, when 3 wt.% PCP-MCN was added to Nafion, the power density of a single-cell fabricated with this composite membrane reaches impressively 0.480, 1.098 W/cm2 under 40% RH, 100% RH at 60 °C, respectively, guaranteeing it to be a promising proton exchange membrane.

An ultra-high strain rate (104 s−1) dynamic plastic deformation treatment at liquid nitrogen temperature (LNT-DPD) followed by annealing is carried out to obtain dual heterogeneity of grain size and dislocation density in an equiatomic CrCoNi medium entropy alloy (MEA). Such extreme loading conditions resulted in extensive phase transformation in this MEA. Subsequent annealing at 650 °C for 1 h further induced reverse phase transformation and partial recrystallization, forming a complex heterogeneous microstructure characterized by nested trimodal grain sizes and partitioned dislocation density. A superior yield strength of ∼800 MPa and a good ductility of ∼40% were simultaneously achieved in this heterogeneous alloy. In order to reveal the effects of grain size and dislocation density distributions on the mechanical property improvements, the underlying deformation mechanisms were systematically discussed. High density of geometrically necessary dislocations (GNDs) would be induced in complex heterogeneous structures during tensile deformation due to strain gradients or partitioning between different regions, which would lead to additional strengthening and work hardening. These results provide a novel approach to overcome the strength-ductility trade-off dilemma for FCC-structured MEAs.

Although microsurgical vasoepididymostomy (MVE) is an effective treatment for epididymal obstructive azoospermia, some patients may experience delayed patency or suboptimal semen parameters after patency. However, research into patency time, semen quality postpatency, and associated influencing factors remains limited. This study aimed to address these issues by evaluating 181 patients who underwent at least one-sided MVE employing asingle-armed longitudinal intussusception vasoepididymostomy technique, with a follow-up period of over 12 months for 150 patients. The overall patency rate was 75.3%, with 86.0% of patients achieving patency within 6 months following MVE. Unexpectedly, factors such as age, history of epididymitis, duration of surgery, side of anastomosis, sperm motility in epididymal fluid, and the site of anastomosis showed no correlation with patency time. Nonetheless, our univariate and multivariate linear regression analysis indicated that only the site of anastomosis was positively correlated with and could independently predict postoperative total motile sperm count. Therefore, the site of anastomosis might serve as a predictor for optimal postoperative semen quality following the MVE procedure.

Abstract Interleukin-33 (IL-33) is a pleiotropic molecule that plays various roles in the body. However, how exogenous IL-33 changes the tumor immune microenvironment remains unclear. Our study revealed that exogenous IL-33 exerts anti-tumor effects and effectively suppresses the progression of subcutaneous melanoma. scRNA-seq analysis revealed that exogenous IL-33 reduced neutrophils accumulation, thereby improving the inhibitory immune environment. Flow cytometry analysis revealed that exogenous IL-33 significantly increased the proportion of eosinophils and group 2 innate lymphoid cells (ILC2s). In addition, we identified genes encoding major histocompatibility complex (MHC) class II molecules in this group of ILC2s, suggesting that ILC2s may play a role in antigen presentation. In Il7r Cre Arg1 flox/flox mice, the decrease of ILC2s led to a reduction in the proportion of eosinophils. Furthermore, we found that exogenous IL-33 effectively promoted the differentiation of ILC2s and their accumulation in tumors, thereby enhancing the anti-tumor immune response. These findings may pave the way for developing new cancer immunotherapies that use IL-33 as an activator to enhance anti-tumor immune responses.

Abstract HOX transcript antisense RNA (HOTAIR) is upregulated in glioblastoma (GBM) and associated with temozolomide (TMZ) resistance. However, the mechanisms underlying HOTAIR-mediated TMZ resistance remains poorly understood. HOTAIR expression in glioma-related public datasets and drug response estimation were analyzed using bioinformatics. These findings were verified by overexpressing HOTAIR in TMZ-sensitive U251 cells and/or silencing HOTAIR in resistant U251 cells (U251R). The cytotoxic effects were evaluated using cell viability assay and flow cytometry analysis of cell cycle and apoptosis. In this study, we found that HOTAIR was upregulated in TMZ-resistant GBM cell lines and patients with high HOTAIR expression responded poorly to TMZ therapy. HOTAIR knockdown restored TMZ sensitivity in U251R cells, while HOTAIR overexpression conferred TMZ resistance in U251 cells. Wnt/β-catenin signaling was enriched in patients with high HOTAIR expression; consistently, HOTAIR positively regulated β-catenin expression in U251 cells. Moreover, HOTAIR-mediated TMZ resistance was associated with increased MGMT protein level, which resulted from the HOTAIR/miR-214-3p/β-catenin network. Besides, GBM with high HOTAIR expression exhibited sensitivity to methotrexate. Methotrexate enhanced TMZ sensitivity in U251R cells, accompanied by reduced expression of HOTAIR and β-catenin. Thus, we conlcude that HOTAIR is a risk factor for TMZ resistance and methotrexate may represent a potential therapeutic drug for patients with high HOTAIR expression level.

Abstract While some literature has provided limited information about the potential cardiovascular risk and immune-related adverse events (irAEs) risk associated with PD-1/PD-L1 inhibitors in the treatment of Head and Neck Squamous Cell Carcinoma (HNSCC), the exact relevance is still uncertain. To assess the pharmacovigilance (PV), constituent ratio, severity, and reaction outcomes of major adverse cardiovascular events (MACE) and immune-related adverse events (irAEs) related to PD-1/PD-L1 inhibitors for HNSCC reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). We analyzed reports of cardiovascular adverse events and irAEs associated with drug therapy for HNSCC submitted to FAERS from the 1st quarter 2015 to the 3rd quarter of 2023. Three PD-1/PD-L1 inhibitors were identified: nivolumab, pembrolizumab and durvalumab. Our primary composite endpoint was the PV of MACE and irAEs related to PD-1/PD-L1 inhibitors in the treatment of HNSCC, and the secondary endpoint was PV of other cardiovascular events. The software implemented was STATA 17.0 MP. 19,372 suspected drug-adverse event reports related to drug treatment in patients with HNSCC were identified, of which 916 reports were cardiovascular events, including 555 reports of MACE and 361 reports of other cardiovascular events. The PV signal regarding MACE was detected in durvalumab (PRR = 2.12, 95% CI: 1.24–3.61; χ2 = 7.71; ROR = 2.19, 95% CI: 1.24–3.86; IC = 1.01; IC025 = 0.07) but not in nivolumab and pembrolizumab. The constituent ratio of MACE in all adverse events caused by nivolumab (OR = 0.38, 95% CI: 0.19–0.73) and pembrolizumab (OR = 0.48, 95% CI: 0.23–0.99) was significantly decreased, compared with durvalumab. A PV signal about other cardiovascular events was detected in durvalumab (PRR = 3.04, 95% CI: 1.73–5.31; χ2 = 16.13; ROR = 3.15, 95% CI: 1.74–5.70; IC = 1.46; IC025 = 0.48), but it was not detected in nivolumab or pembrolizumab. The constituent ratio of other cardiovascular events in all adverse events caused by nivolumab (OR = 0.25, 95% CI: 0.13–0.48) and pembrolizumab (OR = 0.40, 95% CI: 0.20–0.80) was significantly decreased, compared with durvalumab. The constituent ratio of other cardiovascular events in all adverse events caused by nivolumab (OR = 0.61, 95% CI: 0.38–0.99) was significantly decreased, compared with pembrolizumab. There were 40 cases of hypertension. A PV signal about hypertension was detected in pembrolizumab (PRR = 3.72, 95% CI: 1.87–7.43; χ2 = 15.99; ROR = 3.75, 95% CI: 1.87–7.51; IC = 1.53, IC025 = 0.45), but it was not detected in nivolumab. The constituent ratio of hypertension in all adverse events caused by nivolumab (OR = 0.09, 95% CI: 0.09–0.39) was significantly decreased, compared with pembrolizumab. There were 737 cases of irAEs. A PV signal about irAEs was detected in nivolumab (PPR = 1.27, 95% CI: 1.05–1.53; χ2 = 6.38; ROR = 1.28, 95% CI: 1.06–1.56; IC = 0.29, IC025 = −0.00) and pembrolizumab (PPR = 2.20, 95% CI: 1.79–2.71; χ2 = 56.55; ROR = 2.31, 95% CI: 1.84–2.88; IC = 1.03; IC025 = 0.68), but it was not detected in durvalumab. The constituent ratio of irAEs in all adverse events caused by nivolumab (OR = 0.58, 95% CI: 0.44–0.76) significantly decreased, compared with pembrolizumab. By comparing the PV signals, constituent ratio, severity, and reaction outcome of the three drugs, we suppose that nivolumab can be used as the safest PD-1/PD-L1 inhibitor for HNSCC.

Abstract Mutations in GBA1 encoding the lysosomal enzyme β-glucocerebrosidase (GCase) are among the most prevalent genetic susceptibility factors for Parkinson’s disease (PD), with 10–30% of carriers developing the disease. To identify genetic modifiers contributing to the incomplete penetrance, we examined the effect of 1634 human transcription factors (TFs) on GCase activity in lysates of an engineered human glioblastoma line homozygous for the pathogenic GBA1 L444P variant. Using an arrayed CRISPR activation library, we uncovered 11 TFs as regulators of GCase activity. Among these, activation of MITF and TFEC increased lysosomal GCase activity in live cells, while activation of ONECUT2 and USF2 decreased it. While MITF, TFEC, and USF2 affected GBA1 transcription, ONECUT2 might control GCase trafficking. The effects of MITF, TFEC, and USF2 on lysosomal GCase activity were reproducible in iPSC-derived neurons from PD patients. Our study provides a systematic approach to identifying modulators of GCase activity and deepens our understanding of the mechanisms regulating GCase.

Abstract Background Although de novo metastatic breast cancer (dnMBC) is acknowledged as a heterogeneous disease, the current staging systems do not distinguish between patients within the M1 or stage IV category. This study aimed to refine the M1 category and prognostic staging for dnMBC to enhance prognosis prediction and guide the choice of locoregional treatment. Methods We selected patients with dnMBC from the SEER database (2010–2019), grouping them into training (N = 8048) and internal validation (N = 3450) cohorts randomly at a 7:3 ratio. An independent external validation cohort (N = 660) was enrolled from dnMBC patients (2010–2023) treated in three hospitals. Nomogram‐based risk stratification was employed to refine the M1 category and prognostic stage, incorporating T/N stage, histologic grade, subtypes, and the location and number of metastatic sites. Both internal and external validation sets were used for validation analyses. Results Brain, liver, or lung involvement and multiple metastases were independent prognostic factors for overall survival (OS). The nomogram‐based stratification effectively divided M1 stage into three groups: M1a (bone‐only involvement), M1b (liver or lung involvement only, with or without bone metastases), and M1c (brain metastasis or involvement of both liver and lung, regardless of other metastatic sites). Only subtype and M1 stage were included to define the final prognostic stage. Significant differences in OS were observed across M1 and prognostic subgroups. Patients with the M1c stage benefited less from primary tumor surgery in comparison with M1a stage. Conclusion Subdivision of the M1 and prognostic stage could serve as a supplement to the current staging guidelines for dnMBC and guide locoregional treatment.

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is a major tumor that seriously threatens the health of the head and neck or mucosal system. It is manifested as a malignant phenotype of high metastasis and invasion caused by squamous cell transformation in the tissue area. Therefore, it is necessary to search for a biomarker that can systematically correlate and reflect the prognosis of HNSCC based on the characteristics of head and neck tumors. Methods Based on TCGA-HNSCC data, R software was used to analyze gene expression, correlation, Venn diagram, immune invasive and immunosuppressive phenotypes respectively. The intrinsic effect of ITGA5 on the malignant phenotype of HNSCC cells was verified by cell experiments. Immunohistochemical images from The Human Protein Atlas (THPA) database display the differences in the expression of related proteins in HNSCC tissues. Based on functional enrichment and correlation analysis, the prognostic value of ITGA5 for HNSCC was explored, and the expression level of ITGA5 may affect the chemotherapy of targeting the PI3K-AKT. Results In this study, the target gene ITGA5 may be identified as a valuable prognostic marker for HNSCC. The results of enrichment analysis showed that ITGA5 was mainly involved in the dynamic process of extracellular matrix, which may affect the migration or metastasis of tumor cells. Meanwhile, ITGA5 may be closely related to the infiltration of M2 macrophages, and its secretory phenotypes TGFB1, PDGFA and PDGFB may affect the immunosuppressive phenotypes of tumor cells, which reflects the systemic influence of ITGA5 in HNSCC. In addition, the expression levels of ITGA5 were negatively correlated with the efficacy of targeting PI3K-AKT chemotherapy. Conclusion ITGA5 can be used as a potential marker to systematically associate with prognosis of HNSCC, which may be associated with HNSCC malignant phenotype, immunosuppression and chemotherapy resistance.

Abstract Background Sarcopenia and osteoarthritis are prevalent age-related diseases that mutually exacerbate each other, creating a vicious cycle that worsens both conditions. Exercise is key to breaking this detrimental cycle. Facing increasing demand for rehabilitation services within this patient demographic, ChatGPT-4 and wearable device may increase the availability, efficiency and personalization of such health care. Aim To evaluate the clinical efficacy and cost-effectiveness of a rehabilitation system implemented on mobile platforms, utilizing the integration of ChatGPT-4 and wearable devices. Methods The study design is a prospective randomized open blinded end-point (PROBE) non-inferiority trial. 278 patients diagnosed with osteoarthritis and sarcopenia will be recruited and randomly assigned to the intervention group and the control group. In the intervention group patients receive mobile phone-based rehabilitation service where ChatGPT-4 generates personalized exercise therapy, and wearable device guides and monitor the patient to implement the exercise therapy. Traditional clinic based face-to-face exercise therapy will be prescribed and implemented in the control group. All patients will receive three-months exercise therapies following the frequency, intensity, type, time, volume and progression (FITT-VP) principle. The patients will be assessed at baseline, one month, three months, and six months after initiation. Outcome measures will include ROM, gait patterns, Visual Analogue Scale (VAS) for pain assessment, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS) for functional assessment, Short-Form Health Survey 12 (SF-12) for quality of life, Minimal Clinically Important Difference (MCID), Patient Acceptable Symptom State (PASS), and Substantial Clinical Benefit (SCB) for clinically significant measures. Discussion A rehabilitation system combining the capabilities of ChatGPT-4 and wearable devices potentially enhance the availability and efficiency of professional rehabilitation services, thus enhancing the therapeutic outcomes for a substantial population concurrently afflicted with sarcopenia and osteoarthritis.

Abstract In both preclinical and clinical settings, dysregulated frontostriatal circuits have been identified as the underlying neural substrates of compulsive seeking/taking behaviors manifested in substance use disorders and behavioral addictions including internet gaming disorder (IGD). However, the neurochemical substrates for these disorders remain elusive. The lack of comprehensive cognitive assessments in animal models has hampered our understanding of neural plasticity in addiction from these models. In this study, combining data from a rat model of compulsive taking/seeking and human participants with various levels of IGD severity, we investigated the relationship between regional glutamate (Glu) concentration and addictive behaviors. We found that Glu levels were significantly lower in the prelimbic cortex (PrL) of rats after 20-days of methamphetamine self-administration (SA), compared to controls. Glu concentration after a punishment phase negatively correlated with acute drug-seeking behavior. In addition, changes in Glu levels from a drug naïve state to compulsive drug taking patterns negatively correlated with drug-seeking during both acute and prolonged abstinence. The human data revealed a significant negative correlation between Glu concentration in the dorsal anterior cingulate cortex (dACC), the human PrL counterpart, and symptoms of IGD. Interestingly, there was a positive correlation between Glu levels in the dACC and self-control, as well as mindful awareness. Further analysis revealed that the dACC Glu concentration mediated the relationship between self-control/mindful awareness and IGD symptoms. These results provide convergent evidence for a protective role of dACC/PrL in addiction, suggesting interventions to enhance dACC glutamatergic functions as a potential strategy for addiction prevention and treatment.

Abstract This study examined the prevalence of HIV late diagnosis (LD) and identified associated factors with LD among people living with HIV (PLWH). We extracted sociodemographic, epidemiological, and immunological information between 2018 and 2021 in Hunan, China from the HIV/AIDS Comprehensive Response Information Management System of China. The chi-squared test and multivariable logistic regression model were used to identify the factors associated with LD. Among 22,504 PLWH, 14,988 (66.6%) were diagnosed late. PLWH aged 50 and older had a higher proportion of LD (71.2%) than the younger group (60.0%). Older age, being male, Han ethnicity, being registered in Western Hunan, being transferred from health facilities, and being infected through heterosexual intercourse were associated with LD. Among PLWH younger than 50 years, apart from the factors mentioned above, individuals who had primary school or lower education, were non-student, and were divorced or widowed were more likely to be diagnosed late. Unlike younger PLWH, these factors were not associated with LD in the older group. But regional disparities in LD were more significant among them. LD in PLWH remains a severe issue, especially among older people. The study findings provided valuable insights into designing programs targeting groups at higher risk of LD to reduce its prevalence.

Abstract Copper (Cu) is used as a cofactor in all organisms, and yet it can be toxic at high intracellular concentrations, causing cell death. Diethyldithiocarbamate (DDC) is a Cu ionophore that can transport Cu effectively into the cell. Copper-diethyldithiocarbamate (Cu-DDC) can treat prostate cancer (PCa) and may correlate with the cell death process. However, the specific Cu-DDC-related cell death genes in PCa are still unknown. Information about the Cu-DDC-related cell death genes was obtained from a previous study. Concurrently, the RNA expression profiles and clinical data were downloaded from public databases such as GEO, TCGA, and CPGEA. Using data from TCGA database, the logistic and lasso regression models were generated using R software. The influence of these genes in affecting PCa progression and prognosis was analyzed. Finally, the expression of these genes was verified in clinical samples. We found five Cu-DDC-related cell death genes associated with the occurrence of PCa from GSE35988, a gene dataset, namely, CDKN2A, PRC1, CDK1, SOX2, and ZNF365. CDKN2A, PRC1, and CDK1 are known to influence PCa patients’ disease-free survival (DFS) status and were overexpressed, whereas SOX2 and ZNF365 were under-expressed in PCa in the different databases. Some of these genes can affect PCa progression. Consistent with the database results, the mRNA and protein expression of CDKN2A, PRC1, and CDK1 was also higher in clinical samples. In conclusion, we identified five hub genes which are important for Cu-DDC-related cell death process that can predict the development of PCa.

Abstract Single-molecule localization microscopy (SMLM) surpasses the diffraction limit by randomly switching fluorophores between fluorescent and dark states, precisely pinpointing the resulted isolated emission patterns, thereby reconstructing the super-resolution images based on the accumulated locations of thousands to millions of single molecules. This technique achieves a ten-fold improvement in resolution, unveiling the intricate details of molecular activities and structures in cells and tissues. Multicolor SMLM extends this capability by imaging distinct protein species labeled with various fluorescent probes, providing insights into structural intricacies and spatial relationships among different targets. This review explores recent advancements in multicolor SMLM, evaluates the strengths and limitations of each variant, and discusses the future prospects.

Abstract Background X-prolyl aminopeptidase 3 (XPNPEP3) mutations are known to cause nephronophthisis-like nephropathy-1 (NPHPL1), a rare autosomal-recessive kidney disease characterized by progressive kidney failure and cystic kidney disease in childhood. The full phenotypic spectrum associated with mutations in XPNPEP3 is not fully elucidated. Case presentation A 13-year-old Chinese female patient with intellectual disability presented with a 2-year history of convulsions and fatigue, with a recent episode of swelling, breathlessness, and nocturnal dyspnea lasting 10 days. The patient was diagnosed with heart failure and kidney failure. Whole exome sequencing revealed a homozygous c.970–2 A > G mutation in XPNPEP3 associated with severe cardiac dysfunction and neurological symptoms, including epilepsy and intellectual disability. Notably, kidney ultrasound did not reveal the typical changes of NPHPL1, and kidney failure was hypothesized to be secondary to cardiac dysfunction rather than primary kidney pathology. Conclusions This case suggests the possible association of additional phenotypic features associated with XPNPEP3 mutations, emphasizing the need for further investigation into the heterogeneous clinical presentations associated with XPNPEP3 mutations. The findings highlight the importance of considering alternative phenotypes in patients with genetic mutations traditionally associated with specific diseases. Segregation and functional analyses are necessary to determine causality between the c.970–2 A > G XPNPEP3 mutation and disease.

We investigated the prognostic importance of noninvasive factors in predicting sperm retrieval failure in idiopathic nonobstructive azoospermia (iNOA). We studied 193 patients with nonobstructive azoospermia who underwent microsurgical testicular sperm extraction. The Chi-square test and Mann–Whitney U tests for clinical parameters and seminiferous tubule distribution were used for between-group comparisons. A logistic regression analysis was conducted to identify predictors of retrieval failure. Area under the receiver operating characteristic curve for each variable was evaluated, and the net clinical benefit was calculated using a clinical decision curve. Patients with iNOA had a lower sperm retrieval rate than those with known causes. Moreover, testicular volume was an independent factor affecting sperm extraction outcomes (odds ratio = 0.79, P < 0.05). The testicular volume cut-off value was 6.5 ml (area under the curve: 0.694). The patients with iNOA were categorized into two groups on the basis of the distribution of seminiferous tubules observed. The sperm retrieval rate and testicular volume were significantly different between the groups with a uniform or heterogeneous tubule distribution. There was also a significant association between a uniform tubule distribution and testicular volume. In conclusion, a testicular volume of more than 6.5 ml effectively predicts microsurgical testicular sperm extraction failure due to a uniform tubule distribution in patients with iNOA.

In view of the energy occurrence structure of “rich coal, poor oil and little gas” in China, and the situation that coal will occupy the dominant position of energy consumption for a long time,The development history of frozen shaft mechanized drilling and blasting is reviewed in the field of coal mining in China. As the main construction method of shaft construction, the application of dynamite greatly improves the drilling efficiency of frozen shaft. The application of supporting large mechanized equipment such as umbrella drilling, rock grabbing machine loading, large derrick and equipment hoisting, and large formwork building, greatly improve the wellbore completion speed; Shaft drilling rig, reverse drilling rig and shaft boring machine as special shaft sinking methods under special formation conditions, also have their own application range. Aiming at the characteristics of water-rich weakly consolidated formation and the development trend of smart mine in western China, there are shortcomings in using freezing & borehole-blasting method and large drilling equipment to develop the shaft of weakly consolidated formation at kilometer level, while using freezing & shaft boring machine is one of the trends of ultra-deep shaft construction. Combining with the construction cases of freezing & shaft boring machine abroad, reasonable suggestions are put forward for shaft excavation of water-rich weak consolidated rock formation in western China. The freezing wall thickness and strength are calculated according to the current design theory, the permanent shaft support adopts double-layer reinforced concrete wall structure, the rock-breaking form of shaft boring machine under low temperature environment, and the method of hierarchical slag discharge to realize the parallel operation of digging - supporting - transporting. Finally, the next research focus of this construction method is put forward. The synergistic mechanism between shaft wall structure and weakly consolidated surrounding rock should be clarified to realize optimization of shaft wall structure, and the support - operation cooperation mode of shaft boring machine to improve shaft excavation and support efficiency and improve informatization level. Realize shaft driving towards mechanization and intelligence.

The cause of asthenozoospermia (AZS) is not well understood because of its complexity and heterogeneity. Although some gene mutations have been identified as contributing factors, they are only responsible for a small number of cases. Radial spokes (RSs) are critical for adenosine triphosphate-driven flagellar beating and axoneme stability, which is essential for flagellum motility. In this study, we found novel compound heterozygous mutations in leucine-rich repeat-containing protein 23 (LRRC23; c.1018C>T: p.Q340X and c.881_897 Del: p.R295Gfs*32) in a proband from a nonconsanguineous family with AZS and male infertility. Diff-Quik staining and scanning electron microscopy revealed no abnormal sperm morphology. Western blotting and immunofluorescence staining showed that these mutations suppressed LRRC23 expression in sperm flagella. Additionally, transmission electron microscopy showed the absence of RS3 in sperm flagella, which disrupts stability of the radial spoke complex and impairs motility. Following in vitro fertilization and embryo transfer, the proband’s spouse achieved successful pregnancy and delivered a healthy baby. In conclusion, our study indicates that two novel mutations in LRRC23 are associated with AZS, but successful fertility outcomes can be achieved by in vitro fertilization-embryo transfer techniques.

Microdissection testicular sperm extraction (mTESE) is commonly performed to retrieve sperm in the testes for assisted reproductive techniques in patients with idiopathic nonobstructive azoospermia (iNOA). However, the success rate of sperm retrieval varies among individuals. We aim to investigate the association between clinical parameters and sperm retrieval outcomes in patients with iNOA. We searched PubMed, EMBASE, and Web of Science from database inception to August 2, 2023. The main measure was whether sperm retrieval was successful in patients with iNOA who underwent mTESE. Pooled estimates of the sperm retrieval rate and weighted mean differences were calculated using random-effects models. The overall sperm retrieval rate was 36.8% (95% confidence interval [CI]: 27.5%–46.0%, I2 = 95.0%) in nine studies comprising 1892 patients with iNOA. No significant differences were found in age, testicular volume, serum total testosterone concentrations, or inhibin B concentrations between positive and negative sperm retrieval outcomes. Lower anti-Müllerian hormone concentrations in patients with iNOA were associated with a positive outcome of mTESE (weighted mean differences: −2.70; 95% CI: −3.94–−1.46, I2 = 79.0%). In conclusion, this study shows a significant relationship between anti-Müllerian hormone and sperm retrieval outcomes in patients with iNOA, while age, testicular volume, total testosterone, and inhibin B show no significant association. These findings have important implications for assessing the potential success of sperm retrieval and selecting appropriate treatment strategies in patients with iNOA.

Abstract To investigate the effects of different typical exogenous salt concentrations on total soil salinity and the growth of Lycium barbarum under brackish water irrigation, and to determine the salinity threshold of irrigated brackish water that is conducive to the normal growth of Lycium barbarum while mitigating soil salinity accumulation. Four typical exogenous salts (NaCl, CaCl2, NaHCO3, Na2SO4) were selected and set at four concentrations (0.1, 0.5, 2.0, 4.0 g L−1) to conduct a field crossover experiments in the downstream region of the Hetao Irrigation District. The results showed that in the same fertility period, the growth rates of new branches, ground diameter, and crown width first increased and then decreased with rising concentrations of NaCl, CaCl2, and Na2SO4, but showed an inverse relationship with NaHCO3 concentrations. Furthermore, increasing salt concentrations linearly reduced the yield of dry fruits from Lycium barbarum and led to a notable accumulation of total soil salts. Utilizing an experimental research approach, a comprehensive analysis of involving multiple growth indices, stable yield, and soil salinity control of Lycium barbarum revealed that optimal growth occurs at salt concentrations of 0.1–0.5 g L−1 for different water quality areas within the irrigation area; using the method of path analysis identified the total soil salt and crown width as the primary direct and indirect factors influencing the yield of Lycium barbarum. The results of this study provide scientific basis and significant theoretical support for the safe and rational utilization of brackish water and cultivation of Lycium barbarum in typical regions with varying saline water qualities of Hetao irrigation area.

Abstract Virulence factor genes (VFGs) play pivotal roles in bacterial infections and have been identified within the human gut microbiota. However, their involvement in chronic diseases remains poorly understood. Here, we establish an expanded VFG database (VFDB 2.0) consisting of 62,332 nonredundant orthologues and alleles of VFGs using species-specific average nucleotide identity ( https://github.com/Wanting-Dong/MetaVF_toolkit/tree/main/databases ). We further develop the MetaVF toolkit, facilitating the precise identification of pathobiont-carried VFGs at the species level. A thorough characterization of VFGs for 5452 commensal isolates from healthy individuals reveals that only 11 of 301 species harbour these factors. Further analyses of VFGs within the gut microbiomes of nine chronic diseases reveal both common and disease-specific VFG features. Notably, in type 2 diabetes patients, long HiFi sequencing confirms that shared VF features are carried by pathobiont strains of Escherichia coli and Klebsiella pneumoniae. These findings underscore the critical importance of identifying and understanding VFGs in microbiome-associated diseases.

Abstract One of the key applications of near-term quantum computers has been the development of quantum optimization algorithms. However, these algorithms have largely been focused on qubit-based technologies. Here, we propose a hybrid quantum-classical approximate optimization algorithm for photonic quantum computing, specifically tailored for addressing continuous-variable optimization problems. Inspired by counterdiabatic protocols, our algorithm reduces the required quantum operations for optimization compared to adiabatic protocols. This reduction enables us to tackle non-convex continuous optimization within the near-term era of quantum computing. Through illustrative benchmarking, we show that our approach can outperform existing state-of-the-art hybrid adiabatic quantum algorithms in terms of convergence and implementability. Our algorithm offers a practical and accessible experimental realization, bypassing the need for high-order operations and overcoming experimental constraints. We conduct a proof-of-principle demonstration on Xanadu’s eight-mode nanophotonic quantum chip, successfully showcasing the feasibility and potential impact of the algorithm.

Abstract Prostate cancer (PCa) is a commonly occurring malignancy in elderly men. Olaparib, a poly ADP-ribose polymerase inhibitor, is utilized in PCa treatment. However, patients often develop resistance to olaparib after a period of treatment. Genetic alterations may play a significant role in this resistance, but the specific genes involved remain unclear. This study collected RNA-sequence data from the Gene Expression Omnibus database on both olaparib-sensitive and -resistant PCa cells to identify genes crucial for resistance. Subsequently, the enriched pathways of these genes were analyzed, and a protein–protein interaction (PPI) network was constructed to identify hub genes. The effect of these hub genes on PCa occurrence, progression, and prognosis was assessed using data from The Cancer Genome Atlas and Chinese Prostate Cancer Genome and Epigenome Atlas databases. Finally, this study validated our findings in clinical PCa samples and cells. From the GSE189186 dataset, 50 upregulated genes and 2 downregulated genes were identified in olaparib-resistant C4-2B and LNCaP cells. Utilizing the PPI network, eight upregulated genes (BBC3, TP53I3, FDXR, DDB2, CDKN1A, GADD45A, ZMAT3, and SESN1) were identified as hub genes for olaparib-resistant PCa cells. Furthermore, some of these genes were central to PCa occurrence, with BBC3 also influencing progression and prognosis. Importantly, BBC3 expression was upregulated in clinical PCa samples and affected PCa cells sensitive to olaparib, suggesting its potential as a predictive marker for PCa development and olaparib resistance.

Abstract China’s large-scale tree planting programs are critical for achieving its carbon neutrality by 2060, but determining where and how to plant trees for maximum carbon sequestration has not been rigorously assessed. Here, we developed a comprehensive machine learning framework that integrates diverse environmental variables to quantify tree growth suitability and its relationship with tree numbers. Then, their correlations with biomass carbon stocks were robustly established. Carbon sink potentials were mapped in distinct tree-planting scenarios. Under one of them aligned with China’s ecosystem management policy, 44.7 billion trees could be planted, increasing forest stock by 9.6 ± 0.8 billion m³ and sequestering 5.9 ± 0.5 PgC equivalent to double China’s 2020 industrial CO2 emissions. We found that tree densification within existing forests is an economically viable and effective strategy and so it should be a priority in future large-scale planting programs.

Abstract Despite recent advances, severe acute pancreatitis (SAP) remains a lethal inflammation with limited treatment options. Here, we provide compelling evidence of GV-971 (sodium oligomannate), an anti-Alzheimer’s medication, as being a protective agent in various male mouse SAP models. Microbiome sequencing, along with intestinal microbiota transplantation and mass cytometry technology, unveil that GV-971 reshapes the gut microbiota, increasing Faecalibacterium populations and modulating both peripheral and intestinal immune systems. A metabolomics analysis of cecal contents from GV-971–treated SAP mice further identifies short-chain fatty acids, including propionate and butyrate, as key metabolites in inhibiting macrophage M1 polarization and subsequent lethal inflammation by blocking the MAPK pathway. These findings suggest GV-971 as a promising therapeutic for SAP by targeting the microbiota metabolic immune axis.

Abstract Biological water-responsive materials that deform with changes in relative humidity have recently demonstrated record-high actuation energy densities, showing promise as high-performance actuators for various engineering applications. However, there is a lack of theories capable of explaining or predicting the stress generated during water-responsiveness. Here, we show that the nanoscale confinement of water dominates the macroscopic dehydration-induced stress of the regenerated silk fibroin. We modified silk fibroin’s secondary structure, which leads to various distributions of bulk-like mobile and tightly bound water populations. Interestingly, despite these structure variations, all silk samples start to exert force when the bound-to-mobile (B/M) ratio of confined water reaches the same level. This critical B/M water ratio suggests a common threshold above which the chemical potential of water instigates the actuation. Our findings serve as guidelines for predicting and engineering silk’s WR behavior and suggest the potential of describing the WR behavior of biopolymers through confined water.

Abstract Psoriasis is a chronic, relapsing, and refractory immune-mediated skin disease with the etiology and pharmaceutical targets remaining unsatisfactorily addressed. Topical herbal-derived compounds, such as tryptanthrin (Tryp), have been considered as an alternative therapy for psoriasis due to their lower costs and fewer side effects compared to other therapies. However, the effectiveness of topically administered drugs is substantially limited by the thickened pathological skin barrier and the low bioavailability of drugs in the deeper layers of the lesion. Ethosomes, being a novel phospholipid-based vesicle system with high content of ethanol, have been implicated in enhancing topical drug absorption and restoring psoriatic lesions. In this study, taking advantages of ethosomes as a soft and malleable drug carrier, we constructed the Tryp-loaded ethosome (Tryp-ES) through a one-step microfluidics-based technique. The optimal formulation of Tryp-ES was achieved by adding amino-acid-derived surfactant sodium lauroyl glutamate, and Tryp-ES exhibited homogeneous particle size and favorable stability at room temperature. In vitro evaluations showed that Tryp of Tryp-ES could be easily internalized into cells and accumulated in cell nuclei, hence inhibited the abnormally proliferated keratinocytes by inducing apoptosis. In vivo and in vitro assessment using psoritic skin of mice revealed that Tryp-ES had preferred skin retention and permeation of loaded drugs within the initial 1 h of topical administration, which could be attributed to transient disintegrations of cell membranes by ethosomes, thus improved cellular fluidity and permeability. Notably, a synergistic effect of ethosomes and Tryp was found in psoriatic mice. Tryp-ES-treated mice showed substantially ameliorated symptoms of psoriasis and reduced pathological alterations due to hyperplasia, inflammation and angiogenesis, without detectable local or systemic toxicities. Interestingly, lipidomics analysis confirmed that the supplementation of phospholipids, as in the form of ethosome vehicles, was an alterantive strategy to relieve psoriatic pathologies. Taken together, this study provides a novel impact for ethosomal topical delivery of Tryp and underlines their potential as an effective therapy for the management of psoriasis.

Abstract In the context of global low-carbon development, reducing rural residential carbon emissions is the key to implementing emission reduction policies. In order to reduce carbon emissions from rural housing, a carbon emission classification method based on residential life cycle assessment is proposed based on the characteristics of rural housing in China. Its innovation lies in achieving precise analysis of carbon emissions from multiple stages of residential design, construction, and use. Secondly, introducing a lifecycle based emission reduction planning strategy to achieve a new pattern of low-carbon emission reduction in rural residential areas. Taking a rural residential building as a case study, in the early stage of implementing emission reduction, the mean values of the initial carbon emissions corresponding to building energy consumption, energy consumption, and resident living habits were 689, 691, and 683, with standard deviations of 81, 79, and 84. After implementing emission reduction plans, the values decreased to 686, 674, and 631, respectively, with standard deviations reduced to 28, 32, and 13. It was evident that emission reduction planning not only significantly reduced the mean carbon emissions but also substantially decreases their variability, enhancing the stability of carbon emissions. This research contributed to a deeper understanding of the carbon emissions from rural residential life cycles and provides theoretical support and data references for the formulation and implementation of more scientific and effective emission reduction planning. Simultaneously, it promoted low-carbon development in rural areas of China, achieving a harmonious coexistence of economic and social development with environmental protection and contributing to global low-carbon development.

Groundwater is an important water supply source in Xining City. Previous works have found that iron-rich groundwater limits water development and utilization. However, few studies focus on the distribution characteristics and mechanism of iron-rich groundwater in different types of aquifers in Xining City. Based on the hydrochemical data of 144 groundwater samples, combined with the geological and hydrogeological conditions, the distribution characteristics and influencing factors of iron content in groundwater in different aquifers were analyzed by methods of statistics and geostatistics. The results show that the exceeding standard ratio of iron in groundwater of unconsolidated sediments aquifer (Area Ⅰ) is 27. 85%, which is 1. 6 times and 2. 7 times higher than that of clastic rocks fissure-pore aquifer (Area Ⅱ) and bedrock aquifer (Area Ⅲ), respectively. The proportion of iron-rich groundwater (concentration greater than 0. 3 mg/L) in construction land area is significantly higher than in areas with other land use types. The redox environment and human activities (such as industrial wastewater, domestic sewage, and infiltration of iron-rich river water) may be the main factors affecting the increase of iron content in groundwater in Area I. In addition to the redox environment, Agricultural nitrogen fertilizer use and domestic sewage discharge are also important factors affecting iron-rich groundwater in Area Ⅱ. The iron-rich groundwater in Area Ⅲ is mainly controlled by redox conditions. On the regional scale, the distribution of iron-rich groundwater presents in bands or spots along the river. The iron deposits releasing in the primary strata and human activities (industrial wastewater) are the main source of iron ions in the shallow groundwater in the study area. The migration and enrichment of iron in groundwater are mainly controlled by redox conditions, and affected by the runoff condition, without relation to pH and salt effect. This study can provide scientific basis for urban water environment management in Xining City and similar arid and semi-arid areas.

Wastewater surveillance (WWS) can leverage its wide coverage, population-based sampling, and high monitoring frequency to capture citywide pandemic trends independent of clinical surveillance. Here we conducted a nine months daily WWS for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 12 wastewater treatment plants (WWTPs), covering approximately 80% of the population, to monitor infection dynamics in Hong Kong, China. We found that the SARS-CoV-2 virus concentration in wastewater was correlated with the daily number of reported cases and reached two pandemic peaks three days earlier during the study period. In addition, two different methods were established to estimate the prevalence/incidence rates from wastewater measurements. The estimated results from wastewater were consistent with findings from two independent citywide clinical surveillance programmes (rapid antigen test (RAT) surveillance and serology surveillance), but higher than the cases number reported by the Centre for Health Protection (CHP) of Hong Kong, China. Moreover, the effective reproductive number (Rt) was estimated from wastewater measurements to reflect both citywide and regional transmission dynamics. Our findings demonstrate that large-scale intensive WWS from WWTPs provides cost-effective and timely public health information, especially when the clinical surveillance is inadequate and costly. This approach also provides insights into pandemic dynamics at higher spatiotemporal resolutions, facilitating the formulation of effective control policies and targeted resource allocation.

Abstract Background and objective Community-acquired pneumonia (CAP) is a common respiratory disease that frequently requires hospitalisation, and is a significant cause of death worldwide. This study aimed to evaluate the usefulness of alpha-1-antichymotrypsin (AACT) as a diagnostic and prognostic biomarker of CAP. Methods We conducted a multicentre prospective cohort study in patients hospitalised with CAP. Plasma AACT levels were measured using a quantitative enzyme-linked immunosorbent assay. Receiver-operating characteristic (ROC) curves and Cox proportional hazards regression were used to assess the association between plasma AACT levels and CAP diagnosis and prognosis. Results A total of 274 patients with CAP were enrolled in the study. AACT levels were elevated in patients with CAP, especially those with severe CAP and non-survivors. The area under the curve (AUC) of AACT and CRP for diagnosing CAP was 0.755 and 0.843. Cox regression showed that CURB-65 and AACT levels were independent predictors of 30-day mortality. ROC curves showed that plasma AACT levels had the highest accuracy for predicting acute respiratory distress syndrome (ARDS), with an AUC of 0.862. Combining AACT with Pneumonia Severity Index and CURB-65 significantly improved their predictive accuracy for predicting 30-day mortality. Conclusion Plasma AACT levels are elevated in patients with CAP, but plasma AACT level is inferior to the C-reactive protein level for diagnosing CAP. The AACT level can reliably predict the occurrence of ARDS and 30-day mortality in patients with CAP.

Introduction: Natural products (NPs) play a crucial role in the development of therapeutic drugs. However, it is still highly challenging to identify the targets of NPs. Besides, NPs usually exert their pharmacological activities via acting on multiple targets or pathways, which also poses great difficulties for the target identification of NPs. Objectives: Inspired by our continuous efforts in designing drug-like protein degraders, this study introduced a successful example for the target identification and drug discovery of natural products evodiamine by employing PROTAC technology. Methods: Taking advantages of proteolysis targeting chimera (PROTAC), herein an integrated strategy combining PROTAC derivatization, quantitative proteomic analysis and binding affinity validation was developed for target identification and drug discovery of antitumor NP evodiamine. Results: In this study, both highly potent PROTACs and negative controls were designed for quantitative proteomic analysis. Furthermore, REXO4 was confirmed as a direct target of 3-fluoro-10-hydroxylevodiamine, which induced cell death through ROS. In addition, the PROTAC 13c effectively degraded REXO4 both in vitro and in vivo, leading to potent antitumor activities and reduced toxic side effects. Conclusion: In summary, we developed an integrated strategy for the target identification and drug discovery of NPs, which was successfully applied to the PROTAC derivatization and target characterization of evodiamine. This proof-of-concept study highlighted the superiority of PROTAC technology in target identification of NPs and accelerated the process of NPs-based drug discovery, exhibiting broad application in NP-based drug development.

Introduction:: Accurate identification of pulmonary arterial hypertension (PAH) in primary care and rural areas can be a challenging task. However, recent advancements in computer vision offer the potential for automated systems to detect PAH from echocardiography. Objectives:: Our aim was to develop a precise and efficient diagnostic model for PAH tailored to the unique requirements of intelligent diagnosis, especially in challenging locales like high-altitude regions. Methods:: We proposed the Chamber Attention Network (CAN) for PAH identification from echocardiographic images, trained on a dataset comprising 13,912 individual subjects. A convolutional neural network (CNN) for view classification was used to select the clinically relevant apical four chamber (A4C) and parasternal long axis (PLAX) views for PAH diagnosis. To assess the importance of different heart chambers in PAH diagnosis, we developed a novel Chamber Attention Module. Results:: The experimental results demonstrated that: 1) The substantial correspondence between our obtained chamber attention vector and clinical expertise suggested that our model was highly interpretable, potentially uncovering diagnostic insights overlooked by the clinical community. 2) The proposed CAN model exhibited superior image-level accuracy and faster convergence on the internal validation dataset compared to the other four models. Furthermore, our CAN model outperformed the others on the external test dataset, with image-level accuracies of 82.53% and 83.32% for A4C and PLAX, respectively. 3) Implementation of the voting strategy notably enhanced the positive predictive value (PPV) and negative predictive value (NPV) of individual-level classification results, enhancing the reliability of our classification outcomes. Conclusions:: These findings indicate that CAN is a feasible technique for AI-assisted PAH diagnosis, providing new insights into cardiac structural changes observed in echocardiography.

In this study, we investigate the burning behavior of titanium during the electroslag remelting (ESR) process and its impact on the titanium content at the endpoint using machine learning. Initially, a comprehensive database was established by collecting data from literature and experiments, encompassing slag system composition, smelting temperature, and material composition content. Subsequently, six machine learning algorithms, including random forest and Bayesian regression, were employed to model the burning loss behavior of titanium. The random forest model, which exhibited optimal mean square error (MSE) performance, was utilized to generate partial dependence plots. These plots, in conjunction with experimental observations and existing studies, facilitated the analysis of key factors influencing titanium burn loss. Furthermore, the same six machine learning models were applied to predict the endpoint titanium content. The Bayesian regression model demonstrated superior performance in terms of R2 and MSE, leading to the derivation of an empirical formula for predicting endpoint titanium content. This empirical formula was subsequently validated, refined, and optimized using a thermodynamic model based on the theory of molecular ion coexistence. The final prediction formula achieved an error margin of 0.123%.

AbstractContext Tabersonine has been investigated for its role in modulating inflammation-associated pathways in various diseases. However, its regulatory effects on triple-negative breast cancer (TNBC) have not yet been fully elucidated.Objective This study uncovers the anticancer properties of tabersonine in TNBC cells, elucidating its role in enhancing chemosensitivity to cisplatin (CDDP).Materials and methods After tabersonine (10 μM) and/or CDDP (10 μM) treatment for 48 h in BT549 and MDA-MB-231 cells, cell proliferation was evaluated using the cell counting kit-8 and colony formation assays. Quantitative proteomics, online prediction tools and molecular docking analyses were used to identify potential downstream targets of tabersonine. Transwell and wound-healing assays and Western blot analysis were used to assess epithelial–mesenchymal transition (EMT) phenotypes.Results Tabersonine demonstrated inhibitory effects on TNBC cells, with IC50 values at 48 h being 18.1 μM for BT549 and 27.0 μM for MDA-MB-231. The combined treatment of CDDP and tabersonine synergistically suppressed cell proliferation in BT549 and MDA-MB-231 cells. Enrichment analysis revealed that the proteins differentially regulated by tabersonine were involved in EMT-related signalling pathways. This combination treatment also effectively restricted EMT-related phenotypes. Through the integration of online target prediction and proteomic analysis, Aurora kinase A (AURKA) was identified as a potential downstream target of tabersonine. AURKA expression was reduced in TNBC cells post-treatment with tabersonine.Discussion and conclusions Tabersonine significantly enhances the chemosensitivity of CDDP in TNBC cells, underscoring its potential as a promising therapeutic agent for TNBC treatment.

AbstractContext Traditional Chinese Medicine (TCM) is effective as a cancer treatment modality. However, this is the first bibliometric analysis of TCM in lymphoma treatment.Objective This study explores the current trends and research topics of TCM in treating lymphoma from 2000 to 2023.Materials and methods We searched within the Web of Science Core Collection (WoSCC) for publications on TCM in lymphoma treatment, spanning 2000 to 2023. Subsequently, we employed a comprehensive approach utilizing CiteSpace software and VOSviewer to visually analyze research trends, authors, institutions, co-cited references, and keywords.Results From January 1, 2000, to August 31, 2023, annual scientific publications on TCM for lymphoma treatment have steadily increased. Among the leading institutions in this field, the Beijing University of Chinese Medicine and the Fujian Medical University occupied the top positions. Regarding the authors, Jun Peng, Jiumao Lin, and Hongwei Chen emerged as the top three contributors. In the co-citation analysis of references, the top three co-cited references were authored by Hanahan D, Elmore S, and Livak KJ with citations numbered 13, 14, and 17, respectively. In particular, keywords reflecting current emerging trends included ‘pathway’, ‘traditional Chinese medicine’, ‘oxidative stress’, and ‘macrophage polarization’.Discussion and conclusions This bibliometric analysis provides a comprehensive overview of TCM for lymphoma treatment. This analysis identified the predominant trends and research topics in the field. The findings are expected to be of significant value for researchers who focus on TCM in lymphoma treatment, helping them better understand the development of this field.

Studies addressing the anatomical values of the supraspinatus outlet area (SOA) and the available supraspinatus outlet area (ASOA) are insufficient. This study focused on precisely measuring the SOA and ASOA values in a sample from the Chinese population using 3D CT (computed tomography) reconstruction. We analyzed CT imaging of 96 normal patients (59 males and 37 females) who underwent shoulder examinations in a hospital between 2011 and 2021. The SOA, ASOA, acromiohumeral distance (AHD), coracohumeral distance (CHD), coracoacromial arch radius (CAR), and humeral head radius (HHR) were estimated, and statistical correlation analyses were performed. There were significant sex differences observed in SOA (men: 957.62 ± 158.66 mm2; women: 735.87 ± 95.86 mm2) and ASOA (men: 661.35 ± 104.88 mm2; women: 511.49 ± 69.26 mm2), CHD (men: 11.22 ± 2.24 mm; women: 9.23 ± 1.35 mm), CAR (men: 37.18 ± 2.70 mm; women: 33.04 ± 3.15 mm), and HHR (men: 22.65 ± 1.44 mm; women: 20.53 ± 0.95 mm). Additionally, both SOA and ASOA showed positive and linear correlations with AHD, CHD, CAR, and HHR (R: 0.304–0.494, all p < 0.05). This study provides physiologic reference values of SOA and ASOA in the Chinese population, highlighting the sex differences and the correlations with shoulder anatomical parameters.

Information on the physicochemical properties of chemical species is an important prerequisite when performing tasks such as process design and product design. However, the lack of extensive data and high experimental costs hinder the development of prediction techniques for these properties. Moreover, accuracy and predictive capabilities still limit the scope and applicability of most property estimation methods. This paper proposes a new Gaussian process-based modeling framework that aims to manage a discrete and high-dimensional input space related to molecular structure representation with the group-contribution approach. A warping function is used to map discrete input into a continuous domain in order to adjust the correlation between different compounds. Prior selection techniques, including prior elicitation and prior predictive checking, are also applied during the building procedure to provide the model with more information from previous research findings. The framework is assessed using datasets of varying sizes for 20 pure component properties. For 18 out of the 20 pure component properties, the new models are found to give improved accuracy and predictive power in comparison with other published models, with and without machine learning.

Abstract Axial velocity gradient (AVG) in the optical coherence tomography angiography (OCTA) signal affects measurement accuracy when the flow is not perpendicular to the scanning beam. We developed a dual beam OCTA method to decouple the contribution of AVG from the decorrelation signal. Decoupling is first verified by phantom experiments which reduces measurement uncertainty from 1.5 to 0.7% (standard deviation). We also tested the method in human skin in vivo and the results indicate that the contribution of AVG to decorrelation signal is reduced.

Abstract Long-read sequencing holds great potential for characterizing complex microbial communities, yet taxonomic profiling tools designed specifically for long reads remain lacking. We introduce Melon, a novel marker-based taxonomic profiler that capitalizes on the unique attributes of long reads. Melon employs a two-stage classification scheme to reduce computational time and is equipped with an expectation-maximization-based post-correction module to handle ambiguous reads. Melon achieves superior performance compared to existing tools in both mock and simulated samples. Using wastewater metagenomic samples, we demonstrate the applicability of Melon by showing it provides reliable estimates of overall genome copies, and species-level taxonomic profiles.

Abstract Aims Compared to primary breast sarcoma (BSs), radiotherapy-induced sarcoma (RIS) is a less frequent type of secondary breast sarcoma. Undifferentiated pleomorphic sarcoma (UPS) is an even rarer occurrence within the RIS category. This study aimed to present the clinicopathologic and molecular features of breast radiotherapy-induced UPS. Methods A retrospective study was conducted at the Third Affiliated Hospital of Soochow University to analyze three patients with radiation-induced undifferentiated pleomorphic sarcoma (UPS) following breast cancer, spanning from 2006 to 2023. The clinical and pathological variables were extracted from the medical records, while immunohistochemistry was employed to analyze the immunophenotypes of these tumors. Genomic characteristics were assessed through DNA and RNA sequencing techniques. Another 15 cases from the literature were also reviewed to better characterize the tumor. Results The affected areas encompass the chest wall and breasts, with an incubation period ranging from 6 to 17 years. The tumor cells exhibit pleomorphism and demonstrate a high degree of pathological mitosis. Notably, two cases displayed an accelerated disease progression, characterized by recurrent tumors and metastases occurring within short intervals of 48 and 7 months respectively subsequent to the initial diagnosis. The two prevailing identified genes were TP53 (2/3, 66.7%) and RB1 (1/3, 33.3%). Through analysis of somatic copy number variation (CNV), it was discovered that two oncogenes, MCL1 (1/3, 33.3%) and MYC (1/3, 33.3%), had experienced gains in CNV. The Tumor Mutational Burden (TMB) values for case 1, case 2, and case 3 were 5.9 mut/Mb, 1.0 mut/Mb, and 3.0 mut/Mb, respectively. Moreover, the analysis of RNA-NGS (next-generation sequencing) revealed the presence of a novel gene fusion, named COL3A1-GULP1, in case 2. Conclusions Based on our thorough analysis of research findings and previous reports, it is evident that radiotherapy-induced UPS exhibits a highly diverse and frequently severe clinical and biological behavior. Identifying tumor formation using genome sequencing can help understand its biological behavior and determine personalized treatments.

Abstract Rheumatoid arthritis (RA) and arthrofibrosis (AF) are both chronic synovial hyperplasia diseases that result in joint stiffness and contractures. They shared similar symptoms and many common features in pathogenesis. Our study aims to perform a comprehensive analysis between RA and AF and identify novel drugs for clinical use. Based on the text mining approaches, we performed a correlation analysis of 12 common joint diseases including arthrofibrosis, gouty arthritis, infectious arthritis, juvenile idiopathic arthritis, osteoarthritis, post infectious arthropathies, post traumatic osteoarthritis, psoriatic arthritis, reactive arthritis, rheumatoid arthritis, septic arthritis, and transient arthritis. 5 bulk sequencing datasets and 4 single-cell sequencing datasets of RA and AF were integrated and analyzed. A novel drug repositioning method was found for drug screening, and text mining approaches were used to verify the identified drugs. RA and AF performed the highest gene similarity (0.77) and functional ontology similarity (0.84) among all 12 joint diseases. We figured out that they share the same key pathogenic cell including CD34 + sublining fibroblasts (CD34-SLF) and DKK3 + sublining fibroblasts (DKK3-SLF). Potential therapeutic target database (PTTD) was established with the differential expressed genes (DEGs) of these key pathogenic cells. Based on the PTTD, 15 potential drugs for AF and 16 potential drugs for RA were identified. This work provides a new perspective on AF and RA study which enhances our understanding of their pathogenesis. It also shed light on their underlying mechanism and open new avenues for drug repositioning studies.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with high morbidity and mortality worldwide. Oxidative injury and mitochondrial dysfunction in the airway epithelium are major events in COPD progression. Methods and results The therapeutic effects of Progesterone (P4) were investigated in vivo and in vitro in this study. In vivo, in a cigarette smoke (CS) exposure-induced COPD mouse model, P4 treatment significantly ameliorated CS exposure-induced physiological and pathological characteristics, including inflammatory cell infiltration and oxidative injury, in a dose-dependent manner. The c-MYC/SIRT1/PGC-1α pathway is involved in the protective function of P4 against CS-induced COPD. In vitro, P4 co-treatment significantly ameliorated H2O2-induced oxidative injury and mitochondrial dysfunctions by promoting cell proliferation, increasing mitochondrial membrane potential, decreasing ROS levels and apoptosis, and increasing ATP content. Moreover, P4 co-treatment partially attenuated H2O2-caused inhibition in Nrf1, Tfam, Mfn1, PGR-B, c-MYC, SIRT1, and PGC-1α levels. In BEAS-2B and ASM cells, the c-MYC/SIRT1 axis regulated P4’s protective effects against H2O2-induced oxidative injury and mitochondrial dysfunctions. Conclusion P4 activates the c-MYC/SIRT1 axis, ameliorating CS-induced COPD and protecting both airway epithelial cells and smooth muscle cells against H2O2-induced oxidative damage. PGC-1α and downstream mitochondrial signaling pathways might be involved.

Abstract There is no effective and noninvasive solution for thrombolysis because the mechanism by which certain thrombi become tissue plasminogen activator (tPA)-resistant remains obscure. Endovascular thrombectomy is the last option for these tPA-resistant thrombi, thus a new noninvasive strategy is urgently needed. Through an examination of thrombi retrieved from stroke patients, we found that neutrophil extracellular traps (NETs), ε-(γ-glutamyl) lysine isopeptide bonds and fibrin scaffolds jointly comprise the key chain in tPA resistance. A theranostic platform is designed to combine sonodynamic and mechanical thrombolysis under the guidance of ultrasonic imaging. Breakdown of the key chain leads to a recanalization rate of more than 90% in male rat tPA-resistant occlusion model. Vascular reconstruction is observed one month after recanalization, during which there was no thrombosis recurrence. The system also demonstrates noninvasive theranostic capabilities in managing pigs’ long thrombi (>8 mm) and in revascularizing thrombosis-susceptible tissue-engineered vascular grafts, indicating its potential for clinical application. Overall, this noninvasive theranostic platform provides a new strategy for treating tPA-resistant thrombi.

Abstract Multiple Myeloma (MM) prognosis has recently improved thanks to the incorporation of new therapies to the clinic. Nonetheless, it is still a non-curable malignancy. Targeting cancer cells with agents inducing cell death has been an appealing alternative investigated over the years, as is the case of TRAIL, an agonist of DR4 and DR5 death receptors. This pathway, involved in apoptosis triggering, has demonstrated efficacy on MM cells. In this research, we have investigated the sensitivity of a panel of MM cells to this agent and generated TRAIL-resistant models by continuous culture of sensitive cells with this peptide. Using genomic and biochemical approaches, the mechanisms underlying resistance were investigated. In TRAIL-resistant cells, a strong reduction in cell-surface receptor levels was detected and impaired the apoptotic machinery to respond to the treatment, enabling cells to efficiently form the Death Inducing Signalling Complex. In addition, an upregulation of the inhibitory protein c-FLIP was detected. Even though the manipulation of these proteins was able to modify cellular responses to TRAIL, it was not complete, pointing to other mechanisms involved in TRAIL resistance.

Images and videos provide a wealth of information for people in production and life. Although most digital information is transmitted via optical fiber, the image acquisition and transmission processes still rely heavily on electronic circuits. The development of all-optical transmission networks and optical computing frameworks has pointed to the direction for the next generation of data transmission and information processing. Here, we propose a high-speed, low-cost, multiplexed parallel and one-piece all-fiber architecture for image acquisition, encoding, and transmission, called the Multicore Fiber Acquisition and Transmission Image System (MFAT). Based on different spatial and modal channels of the multicore fiber, fiber-coupled self-encoding, and digital aperture decoding technology, scenes can be observed directly from up to 1 km away. The expansion of capacity provides the possibility of parallel coded transmission of multimodal high-quality data. MFAT requires no additional signal transmitting and receiving equipment. The all-fiber processing saves the time traditionally spent on signal conversion and image pre-processing (compression, encoding, and modulation). Additionally, it provides an effective solution for 2D information acquisition and transmission tasks in extreme environments such as high temperatures and electromagnetic interference.

Abstract Breast cancer remains a significant global health challenge, and its mechanisms of progression and metastasis are still not fully understood. In this study, analysis of TCGA and GEO datasets revealed a significant increase in CCT2 expression in breast cancer tissues, which was associated with poor prognosis in breast cancer patients. Functional analysis revealed that CCT2 promoted breast cancer growth and metastasis through activation of the JAK2/STAT3 signaling pathway. Additionally, the E3 ubiquitin ligase Trim21 facilitated CCT2 ubiquitination and degradation, significantly reversing the protumor effects of CCT2. Most interestingly, we discovered that exosomal CCT2 derived from breast cancer cells suppressed the activation and proinflammatory cytokine secretion of CD4+ T cell. Mechanistically, exosomal CCT2 constrained Ca2+-NFAT1 signaling, thereby reducing CD40L expression on CD4+ T cell. These findings highlight CCT2 upregulation as a potential driver of breast cancer progression and immune evasion. Our study provides new insights into the molecular mechanisms underlying breast cancer progression, suggesting that CCT2 is a promising therapeutic target and prognostic predictor for breast cancer.

The COVID-19 pandemic has posed severe threats to global sustainable development. However, a comprehensive quantitative assessment of the impacts of COVID-19 on Sustainable Development Goals (SDGs) is still lacking. This research quantified the post-COVID-19 SDG progress from 2020 to 2024 using projected GDP growth and population and machine learning models including support vector machine, random forest, and extreme gradient boosting. The results show that the overall SDG performance declined by 7.7% in 2020 at the global scale, with 12 socioeconomic SDG performance decreasing by 3.0%–22.3% and 4 environmental SDG performance increasing by 1.6%–9.2%. By 2024, the progress of 12 SDGs will lag behind for one to eight years compared to their pre-COVID-19 trajectories, while extra time will be gained for 4 environment-related SDGs. Furthermore, the pandemic will cause more impacts on countries in emerging markets and developing economies than those on advanced economies, and the latter will recover more quickly to be closer to their pre-COVID-19 trajectories by 2024. Post-COVID-19 economic recovery should emphasize in areas that can help decouple economic growth from negative environmental impacts. The results can help government and non-state stakeholders identify critical areas for targeted policy to resume and speed up the progress to achieve SDGs by 2030.