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Returnee faculty experiencing cross-border academic mobility have obtained ample transnational experience in an international academic environment, which may potentially influence their professional development satisfaction after returning to their home countries. Most research has compared returnee faculty's research productivity with their home-trained colleagues. However, the joint impact of local and overseas networks on professional development satisfaction needs to be further explored, particularly how they take advantage of overseas and domestic academic networks in professional development. This study used a mixed-methods approach to explore these issues. In the quantitative research section, a survey of 1307 returnees from 41 top Chinese universities was conducted. Ordinary Least Squares (OLS) and Propensity Score Matching (PSM) models were adopted to probe the influence of the dual academic networks on returnee scholars' professional development and to reveal the causal effect of the alum faculty status, respectively. In the qualitative research section, thirteen returnee faculty from nine Chinese universities participated in interviews. Key findings show that dual academic networks impact returnees' satisfaction with professional development, and network members with different tie strengths played diverse roles. The frequency of contact with former domestic and overseas supervisors and domestic colleagues is positively related to the returnee faculty's professional development satisfaction. Furthermore, the alum faculty status has a negative effect on returnees' professional development satisfaction. Returnees are advised to effectively and intentionally manage the strength of their ties to various roles within the dual academic networks to enhance their professional development satisfaction.

To date, no empirical study has focused on understanding the evolution process of China's college admission policies and clarifying its hidden evolution logic. Based on the advocacy coalition framework (ACF), this study determines different advocacy coalitions and their belief systems during the evolution process of independent enrollment policy, as well as various driving forces that affect the process. The social network analysis methods are adopted to delineate alliance structures formed by actors with different policy beliefs in the policy subsystems which change over time. This study chooses news reports included in the China National knowledge infrastructure (CNKI) database as the data source, and identifies 328 related news reports to be coded in the analysis. This article not only provides the evolution logic of independent enrollment policy, but also bridges the research gap and therefore enriches the broad literature on the application of Advocacy Coalition Framework in Eastern countries.

Based on drilling and logging data, as well as geological experiments, the geological characteristics and factors controlling high-yield and enrichment of hydrocarbons in ultra-deep clastic rocks in the Linhe Depression, Hetao Basin, are studied. The results are obtained in four aspects. First, the inland saline lacustrine high-quality source rocks developed in the Paleogene in the Linhe Depression have the characteristics of early maturity, early expulsion, high hydrocarbon yield, and continuous and efficient hydrocarbon generation, providing an important resource basis for the formation of ultra-high pressure and high-yield reservoirs. Second, the weak compaction, early charging, and weak cementation for pore-preserving, together with the ultra-high pressure for pore-preserving and fracture expansion to improve the permeability, leads to the development of high-quality reservoirs with medium porosity (greater than 15%) and medium permeability (up to 226×10−3 μm2) in the ultra-deep strata (deeper than 6 500 m), which represents a greatly expanded space for oil and gas exploration. Third, the Linhe Formation adjacent to the trough exhibits a low net-to-gross (NTG) and good reservoir-caprock assemblage, and it is overlaid by very thick high-quality mudstone caprock, which are conducive to the continuous and efficient hydrocarbon generation and pressurization and the formation of ultra-high pressure oil and gas reservoirs. Fourth, the most favorable targets for ultra-deep exploration are the zones adjacent to the hydrocarbon generating center of the Paleogene Linhe Formation and with good tectonic setting and structural traps, mainly including the Xinglong faulted structural zone and the Nalinhu faulted buried-hill zone. The significant breakthrough of ultra-deep oil and gas exploration in the Linhe Depression reveals the good potential of ultra-deep clastic rocks in this area, and provides valuable reference for oil and gas exploration of ultra-deep clastic rocks in other areas.

Abstract Honey vaults are useful tools for password management. A vault usually contains usernames for each domain, and the corresponding passwords, encrypted with a master password chosen by the owner. By generating decoy vaults for incorrect master password attempts, honey vaults force attackers with the vault’s storage file to engage in online verification to distinguish the real vaults, thus thwarting offline guessing attacks. However, sophisticated attackers can acquire additional information, such as personally identifiable information (PII) and partial passwords contained within the vault from various data breaches. Since many users tend to incorporate PII in their passwords, attackers may utilize PII to distinguish the real vault. Furthermore, if attackers may learn partial passwords included in the real vault, it can exclude numerous decoy vaults without the need for online verification. Indeed, both leakages pose serious threats to the security of the existing honey vault schemes. In this paper, we explore two attack variants of the inspired attack scenario, where the attacker gains access to the vault’s storage file along with acquiring PII and partial passwords contained within the real vault, and design a new honey vault scheme. For security assurance, we prove that our scheme is secure against one of the aforementioned attack variants. Moreover, our experimental findings suggest enhancements in security against the other attack. In particular, to evaluate the security in multiple leakage cases where both the vault’s storage file and PII are leaked, we propose several new practical attacks (called PII-based attacks), building upon the existing practical attacks in the traditional single leakage case where only the vault’s storage file is compromised. Our experimental results demonstrate that certain PII-based attacks achieve a 63–70% accuracy in distinguishing the real vault from decoys in the best-performing honey vault scheme (Cheng et al. in Incrementally updateable honey password vaults, pp 857–874, 2021). Our scheme reduces these metrics to 41–50%, closely approaching the ideal value of 50%.

Background/purpose: The handheld nonthermal plasma (HNP) treatment may alter the surface properties, bone metabolism, and inflammatory reactions of polyaryletherketone (PAEK) dental implant materials. This study tested whether the HNP treatment might increase the biocompatibility, surface hydrophilicity, surface free energies (SFEs), and the cell adhesion and mineralization capability of PAEK materials. Materials and methods: Disk-shaped samples of titanium (Ti), zirconia (Zr), polyetheretherketone (PEEK [PE]), and polyetherketoneketone (PEKK [PK]) were subjected to HNP treatment and termed as TiPL, ZrPL, PEPL, and PKPL, respectively. Water-surface reactions were examined using a goniometer. MG-63 cells were cultured on all samples to assess the cell viability, cytotoxicity, cell attachment, and mineralization characteristics. The expression of pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) and key mineralization markers (alkaline phosphatase [ALKP], osteopontin [OPN], and dentin matrix protein 1 [DMP1]) was measured using enzyme-linked immunosorbent assay kits. Results: The HNP-treated samples exhibited significantly enhanced surface hydrophilicities and SFEs compared to the untreated samples. The cell viability remained high across all samples, indicating no cytotoxic effects. The HNP treatment significantly enhanced MG-63 cell adherence and proliferation. Elevated levels of ALKP and OPN were observed for the plasma-treated PEPL and PKPL specimens, while DMP1 levels increased significantly only in the PKPL specimen. Pro-inflammatory cytokine levels were low across all samples, suggesting no inflammatory response. Conclusion: The HNP-treated PAEKs have enhanced the surface hydrophilicity and SFEs as well as superior cell adhesion and mineralization capability, and thus may be good clinical dental implant materials.

Spodoptera frugiperda damages crops around the world and has developed resistance to many pesticides. Beauveria bassiana, a fungus that is harmless to humans and the environment, is widely used in pest control. In our study, differentially expressed genes between S. frugiperda larvae, both exposed and unexposed, to B. bassiana were analyzed by transcriptome sequencing. More than 160 Gb of clean data were obtained, and 2767 and 2892 DEGs were identified in LH36vsCK36 and LH144vsCK144, respectively. To explore the roles of glycometabolism and antioxidation-related enzyme genes in S. frugiperda against B. bassiana infection, the expression patterns of those genes when under attack from B. bassiana were analyzed by quantitative real-time PCR. The results of enzyme activity experiments revealed that S. frugiperda larvae exposed to B. bassiana could upregulate these genes to produce more enzymes related to the maintainance of normal glucose metabolism, as well as regulate the expression of detoxification and antioxidant factors to enhance the larvae's detoxification and antioxidant capacity. The result implied that glycometabolism and antioxidation-related enzymes and genes played critical roles in the antifungal immune process of S. frugiperda larvae. This study enhances our understanding of the molecular mechanisms related to regulation of metabolism and provides a basis for exploring new methods to combat antifungal resistance in S. frugiperda.

Abstract The Mw 6.4 and 6.8 Guanshan-Chihshang earthquakes occurred on 17 and 18 September 2022 resulted in prominent surface ruptures within the Longitudinal Valley in eastern Taiwan, particularly along the Yuli fault. Approximately 18 h after the mainshock, we began to document the surface rupture near Yuli Town. Our result suggests the surface rupture formed a confined single left-lateral trace in the town of Yuli, characterized by a series of en échelon right-stepping left-lateral faulting geometry. The rupture of 2022 roughly matches the locations of 1951 surface ruptures inside Yuli Town, with a similar amount of left-lateral cross-fault displacement. North and South of the Yuli residential area, we identified several sections of the surface rupture distributed in the water-saturated paddy fields. The maximum left-lateral displacement recorded across the rupture can reach 1.4 m just south of Yuli, with the fault scarp resembling a high-angle west-dipping fault geometry. In addition to the co-seismic surface ruptures, our repeating cross-fault measurements show significant post-seismic shallow after-slip along the Yuli fault. The amount of post-seismic deformation within 3 months after the mainshock is close to, or even higher than the co-seismic cross-fault displacement, consistent with local witness accounts and post-event field photos which showed continuous damage and displacement of building floors and roads after the earthquake. Such shallow post-seismic slips were also observed along the main fault trace in the 2014 South Napa earthquake, and likely represent the shallow elastoplastic behavior of the sub-vertical fault in the young alluvial sediments.

Abstract Objective This study aims to identify clinical laboratory parameters for the diagnosis of newly diagnosed multiple myeloma (NDMM), establish optimal cutoffs for early screening, and develop a diagnostic model for precise diagnosis. Methods The study conducted a retrospective analysis of 279 NDMM patients and 553 healthy subjects at Zhejiang Province People’s Hospital between January 2008 and June 2023. Multifactor LR was employed to explore clinical laboratory indicators with diagnostic value for NDMM, determine optimal cutoff values and contract a diagnostic model. The diagnostic efficacy and clinical utility were evaluated using receiver operating characteristic curves (ROC), sensitivity, specificity, and other indicators. Results Multifactor analysis revealed that hemoglobin (Hb), albumin (Alb), and platelet distribution width (PDW) were significant diagnostic factors for NDMM. Optimal cutoff values for Hb, Alb, and PDW in MM diagnosis were determined, and the results showed a significant increase in the probability of NDMM diagnosis when Alb was below 39.3 g/L, Hb was below 11.6 g/dL, and PDW was below 14.1 fL. The diagnostic model constructed from the development cohort demonstrated a high area under the ROC curve of 0.960 (95% CI 0.942–0.978) and exhibited good sensitivity (0.860), specificity (0.957). The area under the curve (AUC) value of the diagnostic model in the external validation cohort was 0.979, confirming its good diagnostic efficacy and generalization. Conclusions The optimal cutoff values for Hb, Alb, and PDW and the diagnostic model designed in the study provided good accuracy and sensitivity for the initial screening and diagnosis of NDMM.

Abstract Objective Colorectal cancer (CRC) is a form of malignancy that exhibits a comparatively elevated occurrence and fatality rate. Given the relatively slower progress in diagnostic and therapeutic approaches for CRC, there is a need to investigate more accurate and efficient biomarkers. Methods Core regulatory genes were screened using the TCGA database, and the expression of neurexophilin 4 (NXPH4) and its prognostic implications were validated using tissue microarray staining. The assessment of NXPH4 functions involved a range of experiments, including cellular, organoid, and murine models. Furthermore, a regulatory network between m5C, NXPH4, and HIF1A was established through several in vitro experiments. Results The overexpression of NXPH4 is associated with unfavorable prognoses in patients with CRC and hepatocellular carcinoma. Additionally, it facilitates the progression of malignant tumors both in laboratory settings and in living organisms of colorectal carcinoma. Our research also reveals that NXPH4 mRNA can avoid degradation through RNautophagy, relying on an m5C-dependent mechanism. Moreover, NXPH4 amplifies the HIF signaling pathway and stabilizes HIF1A by competitively binding to PHD4. Conclusions NXPH4, regulated by m5C, promotes malignant tumor progression and regulates the HIF pathway. Consequently, targeting NXPH4 through molecular therapies could potentially serve as an efficacious therapeutic strategy for the management of CRC exhibiting elevated NXPH4 expression. Graphical abstract

Abstract Acute pancreatitis (AP) is a common disease caused by a variety of causes. Is uric acid associated with the onset of AP? The objective of this study was to assess whether uric acid concentration in AP patients was higher than that in healthy population, and whether there were associations between uric acid concentration and serological indicators related to AP. A total of 205 AP patients were included in this study. Two hundred and five people who underwent physical examination in our hospital were randomly selected as controls. We analyzed whether there was difference in uric acid concentrations between the two groups. If the difference was statistically significant, the correlations between uric acid concentration and serological indicators in AP patients was further analyzed. There was significant difference in uric acid concentration (P

The soft-shell clam Mya japonica (Jay, 1857) is a commercially important fishery resource. In this study, we identified the complete mitochondrial genome of M. japonica and performed a phylogenetic analysis to explore its genetic relationship with Mya arenaria. The genome is 21,396 bp in length and contains 13 protein-coding genes (PCGs), 23 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and 5 D-Loop control regions. The atp8 gene was annotated in Myidae for the first time. Notably, the genome contains an additional trnM, consistent with M. arenaria. The length of the cox2 gene is 1,947 bp, which is 513 bp longer than that in M. arenaria. Its base composition is 29.14% A, 37.26% T, 10.89% C, and 22.71% G. Phylogenetic analysis based on 12 PCGs and 2 rRNAs indicates that M. japonica and M. arenaria form a sister group. In this study, the identification and phylogenetic analysis of the complete mitochondrial genome of M. japonica provide significant information for future taxonomic and evolutionary research of the genus Mya.

Abstract Adjacent vertebral fracture (AVF) is a serious complication of percutaneous vertebroplasty (PVP) or kyphoplasty (PKP) for osteoporotic vertebral compression fracture (OVCF). This study aimed to explore the incidence and risk factors of AVF following PVP or PKP in postmenopausal women. The incidence of AVF was determined by spinal radiographic examinations. The potential risk factors of AVF were identified by univariate analysis, followed by multivariate logistic regression analyses to determine the independent risk factors. In total, 674 postmenopausal women who were treated with PVP or PKP from December 2019 to February 2022 were enrolled in the study. Among them, 58 (8.61%) women experienced an AVF following PVP or PKP. After adjusting for confounding factors, BMI (OR [95% CI] 0.863 [0.781–0.952]; p = 0.003), previous history of OVCF (OR [95% CI] 1.931 [1.044–3.571]; p = 0.036), and Hounsfield unit (HU) value (OR [95% CI] 0.979 [0.967–0.990]; p

AIM: To describe the multimodal imaging features, treatment, and outcomes of patients diagnosed with adult-onset Coats disease. METHODS: This retrospective study included patients first diagnosed with Coats disease at ≥18 years of age between September 2017 and September 2021. Some patients received anti-vascular endothelial growth factor (VEGF) therapy (conbercept, 0.5 mg) as the initial treatment, which was combined with laser photocoagulation as needed. All the patients underwent best corrected visual acuity (BCVA) and intraocular pressure examinations, fundus color photography, spontaneous fluorescence tests, fundus fluorescein angiography, optical coherence tomography (OCT), OCT angiography, and other examinations. BCVA alterations and multimodal image findings in the affected eyes following treatment were compared and the prognostic factors were analyzed. RESULTS: The study included 15 patients who were aged 24-72 (57.33±12.61)y at presentation. Systemic hypertension was the most common associated systemic condition, occurring in 13 (86.7%) patients. Baseline BCVA ranged from 2.0 to 5.0 (4.0±1.1), which showed improvement following treatment (4.2±1.0). Multimodal imaging revealed retinal telangiectasis in 13 patients (86.7%), patchy hemorrhage in 5 patients (33.3%), and stage 2B disease (Shield's staging criteria) in 11 patients (73.3%). OCT revealed that the baseline central macular thickness (CMT) ranged from 129 to 964 µm (473.0±230.1 µm), with 13 patients (86.7%) exhibiting a baseline CMT exceeding 250 µm. Furthermore, 8 patients (53.3%) presented with an epiretinal membrane at baseline or during follow-up. Hyper-reflective scars were observed on OCT in five patients (33.3%) with poor visual prognosis. Vision deteriorated in one patient who did not receive treatment. Final vision was stable in three patients who received laser treatment, whereas improvement was observed in one of two patients who received anti-VEGF therapy alone. In addition, 8 of 9 patients (88.9%) who received laser treatment and conbercept exhibited stable or improved BCVA. CONCLUSION: Multimodal imaging can help diagnose adult-onset Coats disease. Anti-VEGF treatment combined with laser therapy can be an option for improving or maintaining BCVA and resolving macular edema. The final visual outcome depends on macular involvement and the disease stage.

Abstract The CRISPR/Cas9 system has shown great potential for treating human genetic diseases through gene therapy. However, there are concerns about the safety of this system, specifically related to the use of guide-free Cas9. Previous studies have shown that guide-free Cas9 can induce genomic instability in vitro. However, the in vivo safety risks associated with guide-free Cas9 have not been evaluated, which is necessary for the development of gene therapy in clinical settings. In this study, we used doxycycline-inducible Cas9-expressing pigs to evaluate the safety risks of guide-free Cas9 in vivo. Our findings demonstrated that expression of guide-free Cas9 could induce genomic damages and transcriptome changes in vivo. The severity of the genomic damages and transcriptome changes were correlate with the expression levels of Cas9 protein. Moreover, prolonged expression of Cas9 in pigs led to abnormal phenotypes, including a significant decrease in body weight, which may be attributable to genomic damage-induced nutritional absorption and metabolic dysfunction. Furthermore, we observed an increase in whole-genome and tumor driver gene mutations in pigs with long-term Cas9 expression, raising the risk of tumor occurrence. Our in vivo evaluation of guide-free Cas9 in pigs highlights the necessity of considering and monitoring the detrimental effects of Cas9 alone as genome editing via the CRISPR/Cas9 system is implemented in clinical gene therapy. This research emphasizes the importance of further study and implementation of safety measures to ensure the successful and safe application of the CRISPR/Cas9 system in clinical practice.

Abstract Background Obesity has become a major global public health challenge. Studies examining the associations between different obesity patterns and the risk of nonalcoholic fatty liver disease (NAFLD) are limited. This study aimed to investigate the relationships between different obesity patterns and the risk of NAFLD in a large male population in the US. Methods Data from the 2017 to March 2020 National Health and Nutrition Examination Survey (NHANES) were utilized. Liver steatosis and fibrosis were assessed with FibroScan using the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM). Steatosis was identified with a CAP value of 248 dB/m or higher. Abdominal obesity was defined by a waist circumference (WC) of 102 cm or more for males and 88 cm or more for females. Overweight was defined as a body mass index (BMI) of 24.0 kg/m2 and above. General obesity was identified with a BMI of 28.0 kg/m2 or higher. Obesity status was categorized into four types: overweight, general obesity, abdominal obesity, and combined obesity. Multivariate logistic regression, adjusting for potential confounders, was used to examine the link between obesity patterns and NAFLD risk. Subgroup analysis further explored these associations. Results A total of 5,858 adults were included. After multivariable adjustment, compared to the normal weight group, the odds ratios (ORs) [95% confidence interval (CI)] for NAFLD in individuals with overweight, general obesity, abdominal obesity, and combined obesity were 6.90 [3.74–12.70], 2.84 [2.38–3.39], 3.02 [2.02–4.51], and 9.53 [7.79–11.64], respectively. Subgroup analysis showed the effect of different obesity patterns on NAFLD risk was stable among individuals with different clinical conditions. In the fully adjusted multivariate logistic regression model, WC was positively associated with NAFLD risk (OR: 1.48; 95% CI: 1.42–1.53; P

Objective: Immune checkpoint inhibitors (ICIs) have become an important treatment option for cancer. However, the predictive power of current biomarkers is limited for treatment response, especially in triple-negative breast cancer (TNBC). Investigation of the tumor microenvironment (TME) may provide biological insights into the response to ICIs by uncovering the interactions among tumor and immune cells. Emerging technologies of spatial transcriptomics (ST) and proteomics allow clinical researchers to better understand the TME. Data Sources and Study Selection: We reviewed the results of articles published in the past 10 years worldwide. Results: Emerging spatial profiling technologies can be classified into image-based and sequencing-based methods, both of which preserve information on tissue architecture with gene expression and/or protein abundance profiles. Here, we reviewed articles studying TNBC using spatial profiling techniques. By integrating spatial profiles, recent studies showed the relevance of gene and protein expression profiles in the TME of different subgroups. These ST and proteomic characteristics were shown to be associated with patients’ survival. Conclusion: The application of spatial profiling techniques to cancer research has significantly advanced our understanding of breast cancer biology, particularly in the context of TNBC. We are confident that the technology has the potential to revolutionize the prediction of treatment outcomes in the near future. By elucidating the nuances within the TME, spatial profiling opens up new possibilities for personalized strategies for immunotherapy.

Objective: To explore the new treatment strategies for radiation proctitis, which is the most common complication of pelvic tumor malignancies. Methods: Four cases of patients with severe radiation proctitis were treated with high-dosage vitamin C (VC, 12–24 ​g/d, iv) combined with cyclooxygenase-2 (cyclooxygenase-2, COX-2) inhibitors. Results: For these four cases, the diarrhea, hematochezia, tenesmus, pain, and other symptoms were significantly improved. The edema of the rectal wall is also significantly improved in the imaging review. Conclusion: The high-dosage VC combined with the treatment of severe radiation proctitis is safe and effective.

Abstract While adaptive immune responses have been studied extensively in SLE (systemic lupus erythematosus), there is limited and contradictory evidence regarding the contribution of natural killer (NK) cells to disease pathogenesis. There is even less evidence about the role of NK cells in the more severe phenotype with juvenile-onset (J)SLE. In this study, analysis of the phenotype and function of NK cells in a large cohort of JSLE patients demonstrated that total NK cells, as well as perforin and granzyme A expressing NK cell populations, were significantly diminished in JSLE patients compared to age- and sex-matched healthy controls. The reduction in NK cell frequency was associated with increased disease activity, and transcriptomic analysis of NK populations from active and low disease activity JSLE patients versus healthy controls confirmed that disease activity was the main driver of differential NK cell gene expression. Pathway analysis of differentially expressed genes revealed an upregulation of interferon-α responses and a downregulation of exocytosis in active disease compared to healthy controls. Further gene set enrichment analysis also demonstrated an overrepresentation of the apoptosis pathway in active disease. This points to increased propensity for apoptosis as a potential factor contributing to NK cell deficiency in JSLE.

Abstract Objective Inflammation, malnutrition, and cancer are intricately interconnected. Despite this, only a few studies have delved into the relationship between inflammatory malnutrition and the risk of death among cancer survivors. This study aimed to specifically investigate the association between the categorically defined Naples prognostic score (NPS) and the prognosis of cancer survivors. Methods Data from 42,582 participants in the National Health and Nutrition Examination Survey (NHANES, 1999–2018) were subjected to analysis. Naples prognostic scores (NPS) were computed based on serum albumin (ALB), total cholesterol (TC), neutrophil to lymphocyte ratio (NLR), and lymphocyte to monocyte ratio (LMR), and participants were stratified into three groups accordingly. Cancer status was ascertained through a self-administered questionnaire, while mortality data were sourced from the National Death Index up to December 31, 2019. Multiple logistic regression was employed to estimate the odds ratio (OR) with a 95% confidence interval (CI) between NPS and cancer prevalence within the U.S. community population. Kaplan-Meier survival analysis and the Log-rank test were utilized to compare survival disparities among the three groups. Additionally, Cox proportional regression was utilized to estimate the hazard ratio (HR) with a 95% CI. Results The incidence of cancers was 9.86%. Among the participants, 8140 individuals (19.1%) were classified into Group 0 (NPS 0), 29,433 participants (69.1%) into Group 1 (NPS 1 or 2), and 5009 participants (11.8%) into Group 2 (NPS 3 or 4). After adjusting for confounding factors, the cancer prevalence for the highest NPS score yielded an odds ratio (OR) of 1.64 (95% CI: 1.36, 1.97) (P(for trend)

At the end of 2022, the adjustment of the coronavirus disease 2019 (COVID-19) pandemic control policy in China resulted in a large-scale increase in public infection. To compare the fertility parameters of male patients before and after the adjustments of the COVID-19 pandemic control policy in China, we collected data on patients’ medical histories and laboratory examinations on their first visits between June 2022 and March 2023 in five different hospitals. Data were divided into five groups according to the timeline of the policy adjustment. The data we collected from male patients included semen quality and serum reproductive hormone levels, and intergroup comparisons were made using the Mann–Whitney U and Chi-square tests. In total, 16 784 cases underwent regular semen analysis, 11 180 had sperm morphology assessments, and 7200 had reproductive hormone analyses. The data showed declining trends in semen volume, sperm motility, and the progressive sperm motility rate after the policy adjustment. Subgroup comparison revealed an initial decrease and gradual recovery in progressive motility rate. Sperm morphology analysis showed increased neck and tail abnormalities after the policy adjustment. No significant change in hormone levels was observed. Following the adjustment of the COVID-19 prevention policy in China, a decline in sperm motility and morphology was observed. This trend may gradually recover over 2 months. After the policy adjustment, reproductive hormone levels were relatively stable throughout, except for an increase in luteinizing hormone (LH). These changes in semen parameters suggest that the policy adjustment had a short- to medium-term impact on male reproductive function.

Abstract Corneal neovascularization (CNV) is one of the common blinding factors worldwide, leading to reduced vision or even blindness. However, current treatments such as surgical intervention and anti-VEGF agent therapy still have some shortcomings or evoke some adverse effects. Recently, SU6668, an inhibitor targeting angiogenic tyrosine kinases, has demonstrated growth inhibition of neovascularization. But the hydrophobicity and low ocular bioavailability limit its application in cornea. Hereby, we proposed the preparation of SU6668 pure nanoparticles (NanoSU6668; size ~135 nm) using a super-stable pure-nanomedicine formulation technology (SPFT), which possessed uniform particle size and excellent aqueous dispersion at 1 mg/mL. Furthermore, mesenchymal stem cell membrane vesicle (MSCm) was coated on the surface of NanoSU6668, and then conjugated with TAT cell penetrating peptide, preparing multifunctional TAT-MSCm@NanoSU6668 (T-MNS). The T-MNS at a concentration of 200 µg/mL was treated for CNV via eye drops, and accumulated in blood vessels with a high targeting performance, resulting in elimination of blood vessels and recovery of cornea transparency after 4 days of treatment. Meanwhile, drug safety test confirmed that T-MNS did not cause any damage to cornea, retina and other eye tissues. In conclusion, the T-MNS eye drop had the potential to treat CNV effectively and safely in a low dosing frequency, which broke new ground for CNV theranostics.

Abstract Ghost imaging in the time domain allows for reconstructing fast temporal objects using a slow photodetector. The technique involves correlating random or pre-programmed probing temporal intensity patterns with the integrated signal measured after modulation by the temporal object. However, the implementation of temporal ghost imaging necessitates ultrafast detectors or modulators for measuring or pre-programming the probing intensity patterns, which are not available in all spectral regions especially in the mid-infrared range. Here, we demonstrate a frequency downconversion temporal ghost imaging scheme that enables to extend the operation regime to arbitrary wavelengths regions where fast modulators and detectors are not available. The approach modulates a signal with temporal intensity patterns in the near-infrared and transfers the patterns to an idler via difference-frequency generation in a nonlinear crystal at a wavelength where the temporal object can be retrieved. As a proof-of-concept, we demonstrate computational temporal ghost imaging in the mid-infrared with operating wavelength that can be tuned from 3.2 to 4.3 μm. The scheme is flexible and can be extended to other regimes. Our results introduce new possibilities for scan-free pump-probe imaging and the study of ultrafast dynamics in spectral regions where ultrafast modulation or detection is challenging such as the mid-infrared and THz regions.

Constructing structure-function relationships is critical for the rational design and development of efficient catalysts for CO2 electroreduction reaction (CO2RR). In2O3 is well-known for its specific ability to produce formic acid. However, how the crystal phase and surface affect the CO2RR activity is still unclear, making it difficult to further improve the intrinsic activity and screen for the most active structure. In this work, cubic and hexagonal In2O3 with different stable surfaces ((111) and (110) for cubic, (120) and (104) for hexagonal) are investigated for CO2RR. Theoretical results demonstrate that the adsorption of reactants on cubic In2O3 is stronger than that on hexagonal In2O3, with the cubic (111) surface being the most active for CO2RR. In experiments, synthesized cubic In2O3 nanosheets with predominantly exposed (111) surfaces exhibited a high HCOO– Faradaic efficiency (87.5%) and HCOO– current density (–16.7 mA cm–2) at –0.9 V vs RHE. In addition, an aqueous Zn-CO2 battery based on a cubic In2O3 cathode was assembled. Our work correlates the phases and surfaces with the CO2RR activity, and provides a fundamental understanding of the structure-function relationship of In2O3, thereby contributing to further improvements in its CO2RR activity. Moreover, the results provide a principle for the directional preparation of materials with optimal phases and surfaces for efficient electrocatalysis.

Abstract Mitochondrial respiration is essential for the survival and function of T cells used in adoptive cellular therapies. However, strategies that specifically enhance mitochondrial respiration to promote T cell function remain limited. Here, we investigate methylation-controlled J protein (MCJ), an endogenous negative regulator of mitochondrial complex I expressed in CD8 cells, as a target for improving the efficacy of adoptive T cell therapies. We demonstrate that MCJ inhibits mitochondrial respiration in murine CD8+ CAR-T cells and that deletion of MCJ increases their in vitro and in vivo efficacy against murine B cell leukaemia. Similarly, MCJ deletion in ovalbumin (OVA)-specific CD8+ T cells also increases their efficacy against established OVA-expressing melanoma tumors in vivo. Furthermore, we show for the first time that MCJ is expressed in human CD8 cells and that the level of MCJ expression correlates with the functional activity of CD8+ CAR-T cells. Silencing MCJ expression in human CD8 CAR-T cells increases their mitochondrial metabolism and enhances their anti-tumor activity. Thus, targeting MCJ may represent a potential therapeutic strategy to increase mitochondrial metabolism and improve the efficacy of adoptive T cell therapies.

Summary: The association between anti-obesity medications (AOMs) as well as their weight-loss effects and cardiovascular outcomes need to be comprehensively investigated. We searched PubMed, Embase, the Cochrane Center Register of Controlled Trials for Studies, and Clinicaltrial.gov website from the inception to April 2024 and included 129 randomized controlled trials (RCTs) of AOMs. When compared with placebo, every 5 kg weight reduction mediated by AOMs was associated with the reduced risks of 3-point major adverse cardiovascular events (relative risk [RR] 0.72, 95% confidence interval [CI] 0.60–0.85), myocardial infarction (RR 0.75, 95% CI 0.60–0.95), stroke (RR 0.60, 95% CI 0.42–0.85), and heart failure (RR 0.71, 95% CI 0.54–0.95). As for glucagon-like peptide 1 receptor agonist (GLP-1RA)-users, similar cardiovascular benefits were also observed with 5 kg weight loss. This study indicated that the weight reductions mediated by AOMs were associated with cardiovascular benefits observed in AOM-users.

Infrared photodetectors (PDs) are widely used in fields such as military, medical, and aerospace. Traditional semiconductor materials including Si, InGaAs, and HgCdTe show high performance in a wide spectral range with the imaging function. Nevertheless, they also have limitations such as low-temperature operation, high cost, and toxicity. Fortunately, two-dimensional (2D) materials with narrow bandgaps featuring adjustable gaps, mechanical flexibility, and superior optoelectronic properties have the potential to bridge the gap between traditional materials in optoelectronic devices. However, 2D materials’ performance with respect to responsivity (Rλ) and external quantum efficiency (EQE) needs improvement. Tantalum nickel selenium (Ta2NiSe5) with a direct bandgap and high carrier mobility has prospects for broadband PD research. This study combines mechanical exfoliation and micro-nano-processing technology to prepare Ta2NiSe5 nanosheets and design a Ta2NiSe5-based PD, which has a broadband light response from 520 to 1550 nm with an Rλ value of up to 1.07 A/W. The highest EQE of the PD is 2.55, with the lowest noise equivalent power of 2.39 × 10−12 W/Hz1/2 and the highest specific detectivity (D*) of 9.3 × 108 cm Hz1/2/W. The response speed is stable with low power consumption, and the PD can perform high-resolution imaging through different liquids. Hence, Ta2NiSe5-based PDs have photoelectric properties including broadband detection, high responsiveness, and low-light detection, with a broad range of application in new optoelectronics.

Objective Readmission to the coronary care unit (CCU) has significant implications for patient outcomes and healthcare expenditure, emphasizing the urgency to accurately identify patients at high readmission risk. This study aims to construct and externally validate a predictive model for CCU readmission using machine learning (ML) algorithms across multiple hospitals. Methods Patient information, including demographics, medical history, and laboratory test results were collected from electronic health record system and contributed to a total of 40 features. Five ML models: logistic regression, random forest, support vector machine, gradient boosting, and multilayer perceptron were employed to estimate the readmission risk. Results The gradient boosting model was selected demonstrated superior performance with an area under the receiver operating characteristic curve (AUC) of 0.887 in the internal validation set. Further external validation in hold-out test set and three other medical centers upheld the model's robustness with consistent high AUCs, ranging from 0.852 to 0.879. Conclusion The results endorse the integration of ML algorithms in healthcare to enhance patient risk stratification, potentially optimizing clinical interventions, and diminishing the burden of CCU readmissions.

PurposeStudies have demonstrated that hormonal imbalance, such as elevated level of estrogen or reduced level of progesterone, was the main inducing factor of uterine leiomyoma (UL) development and some cancers. UL has been reported to be associated with several cancers in observational studies. However, the causal associations between UL and cancers remain unclear.MethodsA two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal associations between UL and 16 site-specific cancers using the public databases. Four methods, namely, the inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode, were applied in our MR analysis. Sensitivity tests were also performed to evaluate the robustness of these causal associations.ResultsThe IVW analysis indicated that genetically predicted UL increased the risk of low malignant potential ovarian cancer [odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.06–1.40, p = 0.004], serous ovarian cancer (OR = 1.29, 95% CI: 1.10–1.52, p = 0.002), invasive mucinous ovarian cancer (OR = 1.24, 95% CI: 1.08–1.44, p = 0.003), clear cell ovarian cancer (OR = 1.25, 95% CI: 1.03–1.51, p = 0.023), breast cancer (OR = 1.07, 95% CI: 1.02–1.11, p = 0.002), and brain tumor (OR = 1.23, 95% CI: 1.06–1.42, p = 0.007). Conversely, genetically predicted UL reduced the risk of gastric cancer (OR = 0.91, 95% CI: 0.85–0.98, p = 0.008). The causal effects were consistent in the sensitivity analysis.ConclusionsOur results demonstrated that UL exhibits a causal relationship with high risk of several cancers. We suggest reinforcing the cancer screening in UL patients to enable the early detection of cancers.

This study compares how a modified distributed Bragg reflector (DBR) and yellow color filter (Y-CF) increase the color purity, viewing angle, and brightness of the quantum dot color conversion layer (QDCC) for micro-LED displays. We designed and built a 53-layer high-performance modified DBR with almost total blue leakage filtering (T %: 0.16 %) and very high G/R band transmittance (T %: 96.97 %) for comparison. We also use a Y-CF that filters blue light (T %: 0.84 %) and has good G/R band transmittance (T %: 94.83 %). Due to DBR's angle dependency effect, the modified DBR/QDCC structure offers a remarkable color gamut (117.41 % NTSC) at the forward viewing angle, but this rapidly diminishes beyond 30°. The Y-CF/QDCC structure retains 116 % NTSC color at all viewing angles. Because of its consistent color performance at all viewing angles, sufficient brightness, and outstanding color gamut, the Y-CF/QDCC structure is the best option for contemporary QDCC-based micro-LED displays.

Abstract Novel active DNA transposons, such as Spy transposons from the PHIS superfamily, are identified through bioinformatics in this study. The native transposases cgSpy and cvSpy displayed transposition activities of approximately 85% and 35% compared to the hyperactive piggyBac transposase (hyPB). The cgSpy transposon showed unique characteristics, including a lack of overproduction inhibition and reduced efficiency for insertion sizes between 3.1 to 8.5 kb. Integration preferences of cgSpy are found in genes and regulatory regions, making it suitable for genetic manipulation. Evaluation in T‐cell engineering demonstrated that cgSpy‐mediated chimeric antigen receptor (CAR) modification is comparable to the PB system, indicating its potential utility in cell therapy. This study unveils the promising application of the active native transposase, Spy, from Colletes gigas, as a valuable tool for genetic engineering, particularly in T‐cell manipulation.

Treatments of inflammatory bowel disease (IBD) are diverse, but their efficacy is limited, and it is therefore urgent to find better therapies. Controlling mucosal inflammation is a must in IBD drug treatment. The occurrence of anti-tumor necrosis factor α (TNF-α) monoclonal antibodies has provided a safer and more efficacious therapy. However, this kind of treatment still faces failure in the form of loss of response. β-Carboline alkaloids own an anti-inflammatory pharmacological activity. While Kumujan B contains β-carboline, its biological activity remains unknown. In this study, we attempted to determine the anti-inflammatory effects of Kumujan B using both the TNF-α- induced in vitro inflammation and DSS-induced in vivo murine IBD models. Our data show that Kumujan B attenuated the expression of interleukin 1β (IL-1β) and interleukin 6 (IL-6) induced by TNF-α in mouse peritoneal macrophages. Kumujan B suppressed c-Jun N-terminal protein kinases (JNK) signaling, especially c-Jun, for anti-inflammatory response. Furthermore, Kumujan B promoted K11-linked ubiquitination and degradation of c-Jun through the proteasome pathway. In an in vivo study, Kumujan B inhibited the expression of IL-1β, IL-6, and TNF-α and improved the colon barrier function in dextran sulfate sodium salt (DSS)-induced experimental mice colitis. Kumujan B exhibited in vivo and in vitro anti-inflammatory effects, making it a potential therapeutic candidate for treating IBD.

Study region: The Daliang Mountain region, characterized by its widespread debris flow-pone catchments, is the primary sediment source area for the upper reaches of the Yangtze River, and has experienced intensive human activity over the past half-century. Study focus: Here, we combined lake deposits with sediment source areas to quantify the sediment source and corresponding sediment yield (SY) in response to recent human impacts in a typical debris flow-prone catchment located in the Daliang Mountain region, Southwest China. The fingerprinting techniques, incorporating geochemical elements and their specific ratios, were used to characterize the sediment provenances and corresponding SY. New hydrological insight for the region: The results indicated that gully erosion was the major sediment provenance (90.10 %) in the catchment, followed by cultivated land (6.76 %) and forested land (3.14 %) for the studied period. The temporal variations of SY showed two distinctive erosional stages in response to different human activities over the past 70 years, namely 1950−2004 and 2004−2020. Greater SY values, dominated by gully erosion, occurred from 1950 to 2004, implying that both critical national activities and revegetation projects have limited effects on surface sediment generation. In contrast, gully activity and resulting SY have sharply decreased since 2004 following the implementation of check dams. These comparisons indicate a central role of the check dam in reducing gully activity. The findings have important implications for policymakers to optimize the spatial layout of future soil conservation strategies in the region.

Abstract Objective To systematically evaluate the difference in clinical efficacy between two surgical approaches, oblique lateral approach and intervertebral foraminal approach, in the treatment of degenerative lumbar spondylolisthesis. Methods English databases, including PubMed, Cochrane, Embase, and Web of Science, were systematically searched using keywords such as "oblique lumbar interbody fusion" and "transforaminal lumbar interbody fusion." Concurrently, Chinese databases, including CNKI, WanFang data, VIP, and CBM, were also queried using corresponding Chinese terms. The search spanned from January 2014 to February 2024, focusing on published studies in both Chinese and English that compared the clinical efficacy of OLIF and TLIF. The literature screening was conducted by reviewing titles, abstracts, and full texts. Literature meeting the inclusion criteria underwent quality assessment, and relevant data were extracted. Statistical analysis and a meta-analysis of the observational data for both surgical groups were performed using Excel and RevMan 5.4 software. Findings revealed a total of 14 studies meeting the inclusion criteria, encompassing 877 patients. Of these, 414 patients were in the OLIF group, while 463 were in the TLIF group. Meta-analysis of the statistical data revealed that compared to TLIF, OLIF had a shorter average surgical duration (P 0.05) and fusion rates (P > 0.05). Conclusion When treating degenerative lumbar spondylolisthesis, OLIF demonstrates significant advantages over TLIF in terms of shorter surgical duration, reduced intraoperative bleeding, shorter hospital stay, superior improvement in postoperative VAS and ODI scores, better restoration of disc height, and more effective correction of lumbar lordosis.

Abstract Background Cellular senescence frequently occurs during anti-cancer treatment, and persistent senescent tumor cells (STCs) unfavorably promote tumor progression through paracrine secretion of the senescence-associated secretory phenotype (SASP). Extracellular vesicles (EVs) have recently emerged as a novel component of the SASP and primarily mediate the tumor-promoting effect of the SASP. Of note, the potential effect of EVs released from STCs on tumor progression remains largely unknown. Methods We collected tumor tissues from two cohorts of colorectal cancer (CRC) patients to examine the expression of p16, p21, and SERPINE1 before and after anti-cancer treatment. Cohort 1 included 22 patients with locally advanced rectal cancer (LARC) who received neoadjuvant therapy before surgical resection. Cohort 2 included 30 patients with metastatic CRC (mCRC) who received first-line irinotecan-contained treatment. CCK-8, transwell, wound-healing assay, and tumor xenograft experiments were carried out to determine the impacts of EVs released from STCs on CRC progression in vitro and in vivo. Quantitative proteomic analysis was applied to identify protein cargo inside EVs secreted from STCs. Immunoprecipitation and mass spectrometer identification were utilized to explore the binding partners of SERPINE1. The interaction of SERPINE1 with p65 was verified by co-immunoprecipitation, and their co-localization was confirmed by immunofluorescence. Results Chemotherapeutic agents and irradiation could potently induce senescence in CRC cells in vitro and in human CRC tissues. The more significant elevation of p16 and p21 expression in patients after anti-cancer treatment displayed shorter disease-free survival (DFS) for LARC or progression-free survival (PFS) for mCRC. We observed that compared to non-STCs, STCs released an increased number of EVs enriched in SERPINE1, which further promoted the progression of recipient cancer cells. Targeting SERPINE1 with a specific inhibitor, tiplaxtinin, markedly attenuated the tumor-promoting effect of STCs-derived EVs. Additionally, the patients with greater increment of SERPINE1 expression after anti-cancer treatment had shorter DFS for LARC or PFS for mCRC. Mechanistically, SERPINE1 bound to p65, promoting its nuclear translocation and subsequently activating the NF-κB signaling pathway. Conclusions We provide the in vivo evidence of the clinical prognostic implications of therapy-induced senescence. Our results revealed that STCs were responsible for CRC progression by producing large amounts of EVs enriched in SERPINE1. These findings further confirm the crucial role of therapy-induced senescence in tumor progression and offer a potential therapeutic strategy for CRC treatment.

Abstract Non-volatile phase-change memory devices utilize local heating to toggle between crystalline and amorphous states with distinct electrical properties. Expanding on this kind of switching to two topologically distinct phases requires controlled non-volatile switching between two crystalline phases with distinct symmetries. Here, we report the observation of reversible and non-volatile switching between two stable and closely related crystal structures, with remarkably distinct electronic structures, in the near-room-temperature van der Waals ferromagnet Fe5−δ GeTe2. We show that the switching is enabled by the ordering and disordering of Fe site vacancies that results in distinct crystalline symmetries of the two phases, which can be controlled by a thermal annealing and quenching method. The two phases are distinguished by the presence of topological nodal lines due to the preserved global inversion symmetry in the site-disordered phase, flat bands resulting from quantum destructive interference on a bipartite lattice, and broken inversion symmetry in the site-ordered phase.

Abstract The genetic basis of human facial variation and craniofacial birth defects remains poorly understood. Distant-acting transcriptional enhancers control the fine-tuned spatiotemporal expression of genes during critical stages of craniofacial development. However, a lack of accurate maps of the genomic locations and cell type-resolved activities of craniofacial enhancers prevents their systematic exploration in human genetics studies. Here, we combine histone modification, chromatin accessibility, and gene expression profiling of human craniofacial development with single-cell analyses of the developing mouse face to define the regulatory landscape of facial development at tissue- and single cell-resolution. We provide temporal activity profiles for 14,000 human developmental craniofacial enhancers. We find that 56% of human craniofacial enhancers share chromatin accessibility in the mouse and we provide cell population- and embryonic stage-resolved predictions of their in vivo activity. Taken together, our data provide an expansive resource for genetic and developmental studies of human craniofacial development.

Abstract Background This study evaluated the utility of using Accreditation Council for Graduate Medical Education (ACGME) Milestones as a formative assessment tool for the fifth- and sixth-grade medical students’ performance in their internal medicine (IM) clerkship and the same students’ performance in their post-graduate year (PGY) IM training. Methods Retrospective data were collected from 65 medical students completing the two-year IM clerkship in the academic years 2019 and 2020 and 26 of the above students completing their PGY-1 training at the same university hospital in the academic year 2021. Data included the assessment results of 7 of the ACGME IM Milestones, information on admitted patients assigned to the students, and surveys of the students’ satisfaction. Results The analysis included 390 assessment results during the IM clerkship and 78 assessment results during the PGY-1 training. Clinical teachers commonly rated level 3 to medical students in the IM clerkship, with PC-2 subcompetency receiving the lowest rating among seven subcompetencies. The levels of most subcompetencies showed stationary in the two-year IM clerkship. Significant improvement was observed in all subcompetencies during the PGY-1 training. The medical students in the second-year IM clerkship expressed higher satisfaction with implementing Milestones than in their first-year IM clerkship and perceived Milestones assessments’ usefulness as learning feedback. Conclusions Using ACGME Milestones as a formative assessment tool in the IM clerkship yielded promising outcomes. Longitudinal follow-up of subcompetencies facilitated tracking students’ development and providing constructive feedback.