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Abstract Photosynthesis requires chloroplasts, in which most proteins are nucleus-encoded and produced via cytoplasmic translation. The translation initiation factor eIF5B gates the transition from initiation (I) to elongation (E), and the Kozak motif is associated with translation efficiency, but their relationship is previously unknown. Here, with ribosome profiling, we determined the genome-wide I-E transition efficiencies. We discovered that the most prevalent Kozak motif is associated with high I-E transition efficiency in Arabidopsis, rice, and wheat, thus implicating the potential of the Kozak motif in facilitating the I-E transition. Indeed, the effects of Kozak motifs in promoting translation depend on HOT3/eIF5B1 in Arabidopsis. HOT3 preferentially promotes the translation of photosynthesis-associated nuclear genes in a Kozak motif-dependent manner, which explains the chloroplast defects and reduced photosynthesis activity of hot3 mutants. Our study linked the Kozak motif to eIF5B-mediated I-E transition during translation and uncovered the function of HOT3 in the cytoplasmic translational control of chloroplast biogenesis and photosynthesis.

Abstract Background This study investigated the factors influencing the prognosis of children with steroid-resistant nephrotic syndrome (SRNS) in patients from the Guangxi region. Methods We retrospectively analyzed clinical and pathological data of 279 patients with SRNS from six tertiary hospitals in Guangxi. Clinical data were compared between initial (I-SRNS) and secondary (S-SRNS) steroid resistance subgroups and Cox regression analysis was used to determine risk factors for chronic kidney disease (CKD) and CKD stage 5 (CKD5) in patients with SRNS. Results The median age of onset was 54 months. Thirty-three patients had extra-kidney manifestations. Fifty-two, 24, 57, 33, and 41 patients had hypertension, acute kidney injury, vitamin D deficiency, high intraocular pressure, and dwarfism, respectively. One hundred eighty-two and 92 patients had I-SRNS and S-SRNS, respectively. There were significant differences in sex, ethnicity, family history, incidence of hematuria, clinical classification, efficacy of immune agents, and prognosis between groups (P

Abstract Angiogenesis is well known to play a critical role in breast cancer. We previously reported that TNFAIP2 activates Rac1 to promote triple-negative breast cancer (TNBC) cell proliferation, migration, and chemoresistance. However, the potential contribution of TNFAIP2 to tumor angiogenesis remains unknown. In this study, we demonstrated that TNFAIP2 promotes TNBC angiogenesis by activating the Rac1-ERK-AP1-HIF1α signaling axis. Under hypoxia, TNFAIP2 activates Rac1 and ERK sequentially. Following that, ERK activates the AP-1 (c-Jun/Fra1) transcription factor. By employing chromatin immunoprecipitation and luciferase reporter assays, we showed that AP-1 directly interacts with the HIF1α gene promoter, thereby enhancing its transcription. The combined application of ERK inhibitors, U0126 or trametinib, with the VEGFR inhibitor Apatinib, additively suppresses angiogenesis and tumor growth of HCC1806 in nude mice. These findings provide new therapeutic strategies for TNBC.

Abstract Triple negative breast cancer is the most malignant subtype of breast cancer and current treatment options are limited. Radiotherapy is one of the primary therapeutic options for patients with TNBC. In this study, we discovered that the E3 ubiquitin ligase, HECTD3, promoted TNBC cell survival after irradiation. HECTD3 collaborated with UbcH5b to promote p62 ubiquitination and autophagy while HECTD3 deletion led to p62 accumulation in the nucleus in response to irradiation, thus inhibiting RNF168 mediated DNA damage repair. Furthermore, the HECTD3/UbcH5b inhibitor, PC3-15, increased the radiosensitivity of TNBC cells by inhibiting DNA damage repair. Taken together, we conclude that HECTD3 promotes autophagy and DNA damage repair in response to irradiation in a p62-denpendent manner, and that inhibition of the HECTD3-p62 axis could be a potential therapeutic strategy for patients with TNBC in addition to radiotherapy.

Mpox is a zoonotic disease caused by the monkeypox virus (MPXV). Diagnosing and treating the disease has become a global health concern requiring close attention to its spread to non-endemic regions. Clinical diagnosis is based on laboratory test results. Conventional detection techniques include real-time quantitative polymerase chain reaction (qPCR), genome sequencing, antigen and antibody identification, and virus isolation. Nevertheless, these methods fall short of rapidly and efficiently identifying MPXV, as they require specialized training, specific laboratory environments, and professional-grade equipment. Emerging technologies offer complementary advantages to meet diverse diagnostic needs, including various point-of-care testing (POCT) approaches and integrating biosensors with rapid detection techniques. This review discusses prospective future research avenues for MPXV detection, examining the advances and challenges of various detection techniques which may contribute to the ongoing elimination of mpox human-to-human transmission and serves as a reference for developing effective prevention and control strategies.

Abstract Background Lung injury and pulmonary fibrosis (PF), frequently arising as sequelae of severe and acute lung disease, currently face a dearth of effective therapeutic potions. Mesenchymal stem cells (MSCs) with immunomodulatory and tissue repair functions have immense potential to treat lung injury and PF. However, the optimal route of administration, timing, and frequency of dosing remain elusive. Human embryonic stem cell-derived immunity-and-matrix-regulatory cells (IMRCs) have shown therapeutic potential for lung injury and PF. Methods To ascertain the optimal therapeutic regimen for IMRCs in PF, we conducted an experimental study. Utilizing a mouse model of PF induced by bleomycin (BLM), IMRCs were administered via either a single or double intravenous (IV) or intratracheal (IT) injection on the first and seventh days post-BLM induction. Results Our findings revealed that IV infusion of IMRCs surpassed IT infusion in enhancing survival rates, facilitating body weight recovery, and optimizing Ashcroft and Szapiel scores among the model mice. Notably, IV administration exhibited a more profound ability to mitigate lung inflammation and fibrosis. Moreover, earlier and more frequent administrations of IMRCs were found to be advantageous in enhancing their therapeutic effects. Specifically, early administration with two IV infusions significantly improved body weight, lung organ coefficient, pulmonary ventilation and diffusion functions, and PF. This was accompanied by an increase in alveolar type I and II epithelial cells and a suppression of macrophage infiltration via CD24. Conclusion Collectively, these results suggested that IMRCs infusion ameliorated lung injury by promoting lung regeneration and inhibiting macrophage infiltration in a route, time, and frequency-dependent manner.

Although serving as the workhorse, MS/MS cannot fully satisfy the analytical requirements of quantitative sub-metabolome characterization. Because more information intrinsically correlates to more structural and concentration clues, here, efforts were devoted to comprehensively tracing and deciphering MS/MS behaviors through constructing triple three-dimensional (3×3D)-MS/MS spectrum. Ginsenosides-targeted metabolomics of notoginseng, one of the most famous edible medicinal plants, was employed as a proof-of-concept. Serial authentic ginsenosides were deployed to build the correlations between 3×3D-MS/MS spectra and structure/concentration features. Through assaying ginsenosides with progressive concentrations using QTOF-MS to configure 1st 3D spectrum, the generations of MS1 spectral signals, particularly multi-charged multimer anions, e.g., [2M–2H]2– and [2M+2HCOO]2– ions, relied on both concentration and the amount of sugar chains. By programming progressive collision energies to the front collision cell of Qtrap-MS device to gain 2nd 3D spectrum, optimal collision energy (OCE) corresponding to the glycosidic bond fission was primarily correlated with the masses of precursor and fragment ions and partially governed by the glycosidation site. The quantitative relationships between OCEs and masses of precursor and fragment ions were utilized to build large-scale quantitative program for ginsenosides. After applying progressive exciting energies to the back collision chamber to build 3rd 3D spectrum, the fragment ion and the decomposition product anion exhibited identical dissociation trajectories when they shared the same molecular geometry. After ginsenosides-focused quantitative metabolomics, significant differences occurred for sub-metabolome amongst different parts of notoginseng. The differential ginsenosides were confirmatively identified by applying the correlations between 3×3D-MS/MS spectra and structures. Together, 3×3D-MS/MS spectrum covers all MS/MS behaviors and dramatically facilitates sub-metabolome characterization from both quantitative program development and structural identification.

Spermidine is a naturally occurring polyamine widely utilized in the prevention and treatment of various diseases. Current spermidine biosynthetic methods have problems such as low efficiency and complex multi-enzyme catalysis. Based on sequence-structure-function relationships, we engineered the widely studied homospermidine synthase from Blastochloris viridis (BvHSS) and obtained mutants that could catalyze the production of spermidine from 1,3-diaminopropane and putrescine. The specific activities of BvHSS and the mutants D361E and E232D + D361E (E232D-D) were 8.72, 46.04 and 48.30 U/mg, respectively. The optimal pH for both mutants was 9.0, and the optimal temperature was 50 °C. Molecular docking and dynamics simulations revealed that mutating aspartic acid at position 361 to glutamic acid narrowed the substrate binding pocket, promoting stable spermidine production. Conversely, mutating glutamic acid at position 232 to aspartic acid enlarged the substrate channel entrance, facilitating substrate entry into the active pocket and enhancing spermidine generation. In whole-cell catalysis lasting 6 h, D361E and E232D-D synthesized 725.3 and 933.5 mg/L of spermidine, respectively. This study offers a practical approach for single-enzyme catalyzed spermidine synthesis and sheds light on the crucial residues influencing homospermidine synthase catalytic activity in spermidine production.

Abstract Background The development of acquired EGFR-TKI treatment resistance is still a major clinical challenge in the treatment of non-small cell lung cancer (NSCLC). This study aimed to investigate the role of HDAC1/FOXK1/miR-33a signaling in EGFR-TKI resistance. Methods The expression levels of miR‐33a, HDAC1, and FOXK1 were examined using quantitative polymerase chain reaction (PCR) and bioinformatics analysis. Cell proliferation, migration, and apoptosis were explored by cell number assay, Transwell, and flow cytometry assays, respectively. After overexpression or knockdown of HDAC1, miR-33a expression in the cells, cell functions were tested. Immunoprecipitation and correlation analyses were used to evaluate the interaction between HDAC1 and FOXK1 protein. The tumor-suppressive role of miR-33a was investigated by animal experiments. Results The suppression of miR-33a increased TKI resistance by affecting cell proliferation, migration, and apoptosis in gefitinib-resistant cells. HDAC1 is the key upstream molecule that inhibits miR-33 expression. HDAC1 upregulation increased gefitinib resistance by its binding to FOXK1 in cells to silence miR-33a expression. MiR-33a overexpression exerts tumor-suppressive effects by negatively regulating ABCB7 and p70S6K1 expression. Moreover, overexpression of miR-33a inhibited tumor growth in a xenograft nude mouse model. Conclusions HDAC1/FOXK1 upregulation and miR-33a silencing are new mechanisms of EGFR-TKI resistance in NSCLC.

Abstract Small extracellular vesicles (sEVs) are important mediators of intercellular communication between tumor cells and their surrounding environment. Furthermore, the mechanisms by which miRNAs carried in tumor sEVs regulate macrophage polarization remain largely unknown. To concentrate sEVs, we used the traditional ultracentrifugation method. Western blot, NanoSight, and transmission electron microscopy were used to identify sEVs. To determine the function of sEVs-miR-487a, we conducted in vivo and in vitro investigations. The intercellular communication mechanism between osteosarcoma cells and M2 macrophages, mediated by sEVs carrying miR-487a, was validated using luciferase reporter assays, transwell assays, and Western blot analysis. In vitro, sEVs enriched in miR-487a and delivered miR-487a to macrophages, promoting macrophage polarization toward an M2-like type, which promotes proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of osteosarcoma cells. In vivo, sEVs enriched in miR-487a facilitate lung metastasis of osteosarcoma. Moreover, plasma miR-487a in sEVs was shown to be a potential biomarker applicable for osteosarcoma diagnosis. In summary, miR-487a derived from osteosarcoma cells can be transferred to macrophages via sEVs, then promote macrophage polarization towards an M2-like type by targeting Notch2 and activating the GATA3 pathway. In a feedback loop, the activation of macrophages accelerates epithelial-mesenchymal transition (EMT), which in turn promotes the migration, invasion, and lung metastasis of osteosarcoma cells. This reciprocal interaction between activated macrophages and osteosarcoma cells contributes to the progression of the disease. Our data demonstrate a new mechanism that osteosarcoma tumor cells derived exosomal-miR-487a which is involved in osteosarcoma development by regulating macrophage polarization in tumor microenvironment (TME).

Abstract To explore the clinical characteristics of patients infected with SARS-CoV-2 nationwide, especially the effect factors of asymptomatic infection and disappearance of clinical symptoms. A total of 66,448 COVID-19 patients in China who have been diagnosed by nucleic acid test or rapid antigen test were surveyed online (December 24, 2022 to January 16, 2023). Our cross-sectional study used descriptive analyses and binary Logistics regression model to assess the correlation between the clinical characteristics and relative factors, including age, gender, pre-existing conditions, reinfection, vaccination and treatment. A total of 64,515 valid questionnaires were collected. Among included participants, 5969 of which were asymptomatic. The symptoms were mainly upper respiratory symptoms, including dry and itchy throat (64.16%), sore throat (59.95%), hoarseness (57.90%), nasal congestion (53.39%). In binary Logistics regression model, we found that male, no pre-existing conditions, reinfection and vaccination have positive correlations with the appearance of asymptomatic COVID-19 patients. In Cox proportional-hazards regression model, considering all clinical symptoms disappeared in 14 days as outcome, we found that ≤ 60 years old, male, no pre-existing conditions, vaccination and adopted treatment have positive correlations with rapid amelioration of clinical symptoms in COVID-19 patients. The clinical symptoms of the participants were mainly upper respiratory symptoms which were according with the infection of Omicron variant. Factors including age, gender, pre-existing conditions and reinfection could influence the clinical characteristics and prognosis of COVID-19 patients. Importantly, vaccination has positive significance for the prevention and treatment of COVID-19. Lastly, the use of Chinese medicine maybe beneficial to COVID-19 patients, however, reasonable guidance is necessary.

OBJECTIVE: The aim of the study was to analyze the clinical data of patients with chronic obstructive pulmonary disease and obstructive sleep apnea overlap syndrome (OS) during hospitalization and to evaluate the risk factors of patients treated with Non-Invasive Ventilation (NIV). METHODS: Demographic and clinical data of patients with confirmed OS during hospitalization were retrospectively collected. The patients were divided into two groups according to whether noninvasive ventilator was used during hospitalization, including OS treated with NIV (244 cases) and OS without NIV (239 cases). The t-test, χ2 test, and Kaplan–Meier curve were used to compare the two groups, and multiple logistic regression was used to analyze the risk factors of NIV in patients with OS. RESULTS: Compared with the OS group without NIV, the pulmonary hypertension, lymphocyte count, and left ventricular ejection fraction% of OS patients with NIV were lower, whereas PCO2, uric acid, C-reactive protein, procalcitonin, and N-terminal pro-B-type natriuretic peptide were higher, with statistical differences (P < 0.05). During hospitalization and follow-up, OS patients with NIV had a longer hospital stay (P < 0.001), and there was no significant difference in the rate of readmission within 28 days. The logistic regression analysis showed that the history of diuretic use, previous history of noninvasive ventilator use, and ischemic heart disease were independent risk factors for NIV treatment in OS patients during hospitalization. CONCLUSION: Patients with OS undergoing NIV during hospitalization exhibited more severe overall illness and had prolonged hospital stays compared to OS patients not receiving NIV. History of diuretic use, history of NIV use, and ischemic heart disease are independent risk factors for NIV treatment in OS patients during hospitalization.

BackgroundThe senescence of alveolar type II epithelial cells is an important driving factor for the progression of silicotic fibrosis, and the regulatory effects of oxamate on the senescence of alveolar type II epithelial cells is still unclear.ObjectiveTo explore whether lactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting senescence of alveolar type II epithelial cellsMethodsThis study was divided into two parts: in vivo experiments and in vitro experiments. In the first part, forty SPF C57BL/6J male mice were randomly divided into four groups with 10 in each group: control group, silicosis model group, low-dose oxamate treatment group, and high-dose oxamate treatment group. The silicotic mouse model was established by intratracheal instillation of 50 μL SiO2 suspension (100 mg·mL−1). The treatment models were prepared by intraperitoneal injection of 100 μL oxamate (225 mmol·L−1 and 1125 mmol·L−1). In the second part, induction of MLE-12 mouse alveolar type II epithelial cells was conducted with SiO2. The in vitro experimental groups were ① SiO2 induction groups: control group, 50 μg·mL−1 SiO2 group, 100 μg·mL−1 SiO2 group, and 200 μg·mL−1 SiO2 group, and ② oxamate treatment groups: control group, SiO2 group (100 μg·mL−1), low-dose oxamate (25 mmol·L−1) treatment group, and high-dose oxamate (50 mmol·L−1) treatment group. Pathological morphology of lung tissues was evaluated after hematoxylin-eosin (HE) staining; deposition of collagen in lung tissues was evaluated after sirius red staining; positive co-expression of prosurfactant protein C (Pro-SPC) and β-galactosidase was detected by immunofluorescence staining; positive expression of β-galactosidase in MLE-12 cells was detected by immunofluorescence staining. The protein expression levels of collagen type I (CoL I), fibronectin1 (FN1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), lactate dehydrogenase A (LDHA), p-ataxia telangiectasia and Rad3-related kinase (ATR), and cyclin-dependent kinase inhibitors p21, and p16 were detected by Western blotting.ResultsCompared with the control group, the protein expression levels of HK2, PKM2, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group and the SiO2-induced MLE-12 cells (P＜0.05). The in vivo studies showed that, compared with the control group, the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the protein expression levels of CoL I, FN1, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group (P＜0.05). Compared with the silicosis model group, the oxamate treatment groups showed significant downregulation of the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the the CoL I, FN1, LDHA, p-ATR, p21, and p16 protein expression levels, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P＜0.05). The in vitro studies showed that, compared with the control group, the proportion of β-galactosidase positive cells and the protein expression levels of p-ATR, p21, and p16 were significantly upregulated in the SiO2-induced group (P＜0.05). Compared with the SiO2 group, the proportion of β-galactosidase positive cells and the LDHA, p-ATR, p21 and p16 protein expression levels were significantly downregulated in the oxamate treatment groups, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P＜0.05).ConclusionLactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting the senescence of alveolar type II epithelial cells.

The influence of various solution annealing treatments on the microstructure and mechanical properties of a new Cr–Mn austenitic stainless steel with 1.15 wt% (C + N) and 0.51 C/N ratio has been investigated. A sequential solution annealing (SSA) treatment is designed to sufficiently dissolve and lower numerous precipitates including carbides and nitrides in the austenite matrix. In this process, the hot-forged steel is firstly solution heat treated at 1120 °C for 2 h, then continuously heated to 1180 °C for 0.5 h, and further heated to 1200 °C for 0.5 h, followed by water quenching. The experimental results show that the austenite grain size increases, and number of precipitates decreases, with increasing temperature and time of solution annealing treatments. The highest impact energy is obtained after this SSA treatment due to a more homogeneous grain distribution, a smaller amount of carbides remaining on the grain boundary, and solid solution strengthening of interstitial (C + N) atoms.

Abstract Zinc oxide nanoparticles (ZNPs) are widely used in sunscreens and nanomedicines, and it was recently confirmed that ZNPs can penetrate stratum corneum into deep epidermis. Therefore, it is necessary to determine the impact of ZNPs on epidermis. In this study, ZNPs were applied to mouse skin at a relatively low concentration for one week. As a result, desmosomes in epidermal tissues were depolymerized, epidermal mechanical strain resistance was reduced, and the levels of desmosomal cadherins were decreased in cell membrane lysates and increased in cytoplasmic lysates. This finding suggested that ZNPs promote desmosomal cadherin endocytosis, which causes desmosome depolymerization. In further studies, ZNPs were proved to decrease mammalian target of rapamycin complex 1 (mTORC1) activity, activate transcription factor EB (TFEB), upregulate biogenesis of lysosome-related organelle complex 1 subunit 3 (BLOC1S3) and consequently promote desmosomal cadherin endocytosis. In addition, the key role of mTORC1 in ZNP-induced decrease in mechanical strain resistance was determined both in vitro and in vivo. It can be concluded that ZNPs reduce epidermal mechanical strain resistance by promoting desmosomal cadherin endocytosis via the mTORC1-TFEB-BLOC1S3 axis. This study helps elucidate the biological effects of ZNPs and suggests that ZNPs increase the risk of epidermal fragmentation. Graphical abstract

IntroductionUreaplasma urealyticum (UU) is a common pathogen associated with genital tract infections in infertile males. However, its impact on semen quality, embryo development, and in vitro fertilization (IVF) outcomes remains underexplored. This study aims to evaluate the effect of male UU infection on semen parameters, embryo development, pregnancy outcomes, and neonatal health in infertile couples.MethodsA retrospective analysis was conducted on 1,215 infertile couples at the First Hospital of USTC. Participants were divided into two groups based on the male partner’s UU infection status: UU-positive (n=249) and UU-negative (n=966). Semen parameters (sperm concentration, motility, morphology, anti-sperm antibodies, DNA stainability) were assessed. Embryo development was evaluated through fertilization rates and blastocyst formation rates. Pregnancy outcomes (clinical pregnancy, live birth rates, miscarriage rate) and neonatal health (gestational age, birth weight, Apgar scores, preterm delivery) were also compared.ResultsSemen parameters, including sperm concentration, motility, and morphology, were similar between the UU-positive and UU-negative groups. However, the UU-positive group had significantly higher levels of anti-sperm antibodies (ASA) (p=0.020) and higher DNA stainability (HDS) (p=0.014). Despite these differences, embryo quality, as measured by fertilization rates and blastocyst formation rates, was not significantly different between the two groups. Pregnancy outcomes, including clinical pregnancy and live birth rates, were also comparable. While the UU-positive group had a slightly higher miscarriage rate, this difference was not statistically significant. Neonatal outcomes, including gestational age, birth weight, Apgar scores, and preterm delivery rate, did not differ significantly between the two groups.DiscussionThe study suggests that while male UU infection may adversely affect certain semen parameters, its impact on IVF outcomes—such as embryo quality, pregnancy rates, and neonatal health—appears to be minimal. These findings support the continued use of IVF as a viable and safe option for infertile couples with male UU infection, as it does not significantly influence reproductive or neonatal outcomes.

IntroductionPatients with Primary Sjögren’s syndrome (pSS) are at a higher risk of thyroid disorders than the general population. This retrospective analysis of 202 patients with pSS was conducted to uncover risk factors associated with thyroid involvement and to create a predictive model for this condition.MethodsWe analyzed 202 patients with pSS from Guang’anmen Hospital, China Academy of Chinese Medical Sciences, with 105 cases of thyroid involvement and 97 without. The Least Absolute Shrinkage and Selection Operator method was used to identify key variables for our risk model. These variables were then subjected to multivariate logistic regression to develop the model. The accuracy of the model was assessed through the C-index, receiver operating characteristic curves, calibration plots, and decision curve analysis, with internal validation via bootstrapping.ResultsHigh-sensitivity C-reactive protein (HCRP), pulmonary disease, pharyngeal dryness, forgetfulness, night sweats, hyperuricemia, nasal dryness, anxiety, Ro52, and aspartate aminotransferase (AST) were incorporated into the nomogram. The model showed robust discrimination and calibration abilities. Decision curve analysis indicated the clinical utility of our nomogram in intervening on the probability thresholds of thyroid disease.ConclusionBy integrating HCRP, pulmonary disease, pharyngeal dryness, forgetfulness, night sweats, hyperuricemia, nasal dryness, anxiety, Ro52, and AST, our thyroid risk nomogram can predict the risk of thyroid involvement in patients with pSS, aiding in more informed treatment strategies.

The kidney plays a crucial role in regulating homeostasis within the human body. Renal cell carcinoma (RCC) is the most common form of kidney cancer, accounting for nearly 90 % of all renal malignancies. Despite the availability of various therapeutic strategies, RCC remains a challenging disease due to its resistance to conventional treatments. Nanotechnology has emerged as a promising field, offering new opportunities in cancer therapeutics. It presents several advantages over traditional methods, enabling diverse biomedical applications, including drug delivery, prevention, diagnosis, and treatment. Lipid nanoparticles (LNPs), approximately 100 nm in size, are derived from a range of lipids and other biochemical compounds. these particulates are designed to overcome biological barriers, allowing them to selectively accumulate at diseased target sites for effective therapeutic action. Many pharmaceutically important compounds face challenges such as poor solubility in aqueous solutions, chemical and physiological instability, or toxicity. LNP technology stands out as a promising drug delivery system for bioactive organic compounds. This article reviews the applications of LNPs in RCC treatment and explores their potential clinical translation, identifying the most viable LNPs for medical use. With ongoing advancement in LNP-based anticancer strategies, there is a growing potential to improve the management and treatment of renal cancer.

This study investigated the expression of calretinin (CR) in the mouse cochlea from embryonic day 17 (E17) to adulthood through immunofluorescence. At E17, CR immunoreactivity was only detected in the inner hair cells (IHCs). At E19, the IHCs and spiral ganglion neurons (SGNs) begin to express CR. At birth, CR immunoreactivity was confined primarily to the IHCs and the majority of the SGNs, as identified by TUJ1, both the cytoplasm and the nucleus of SGNs exhibited CR positivity. At postnatal day 2 (P2), auditory nerve fibers reaching the IHCs were stained for CR. CR continued to be expressed in the IHCs, whereas only single row of outer hair cells (OHCs) were positive for CR. By P5, CR expression was evident in IHCs and the three rows of OHCs, with SGNs soma and their neurite projections also displaying CR immunoreactivity. From P8 through adulthood, CR expression persisted in the SGNs and their afferent neurite projections to the IHCs, as well as in IHCs and OHCs. Dual labeling of CR with afferent nerve marker neurofilament 200 (NF200) demonstrated that NF 200-positive SGN somas were encompassed by CR-labeled plasma membrane of SGNs, and NF 200 was co-localized with CR in the afferent nerve fibers innervating the IHCs. We also described the expression of peripherin, a marker for type II SGNs, in the mouse cochlea at various postnatal stages. Peripherin showed a distinct spatio-temporal expression compared to CR in auditory nerve fibers. No co-expression of peripherin and CR was detected in adult. Dynamic expression patterns of CR in the embryonic and postnatal cochlea supported its roles in cochlear development.

In marine ranching aquaculture, dissolved oxygen (DO) is a crucial parameter that directly impacts the survival, growth, and profitability of cultured organisms. To effectively guide the early warning and regulation of DO in aquaculture waters, this study proposes a hybrid model for spatiotemporal DO prediction named PCA-ISSA-DAM-Bi-GRU. Firstly, principal component analysis (PCA) is applied to reduce the dimensionality of the input data and eliminate data redundancy. Secondly, an improved sparrow search algorithm (ISSA) based on multi strategy fusion is proposed to enhance the optimization ability and convergence speed of the standard SSA by optimizing the population initialization method, improving the location update strategies for discoverers and followers, and introducing a Cauchy-Gaussian mutation strategy. Thirdly, a feature and temporal dual attention mechanism (DAM) is incorporated to the baseline temporal prediction model Bi-GRU to construct a feature extraction network DAM-Bi-GRU. Fourthly, the ISSA is utilized to optimize the hyperparameters of DAM-Bi-GRU. Finally, the proposed model is trained, validated, and tested using water quality and meteorological parameter data collected from a self-built LoRa+5G-based marine ranching aquaculture monitoring system. The results show that: (1) Compared with the baseline model Bi-GRU, the addition of PCA, ISSA and DAM module can effectively improve the prediction performance of the model, and their fusion is effective; (2) ISSA demonstrates superior capability in optimizing model hyperparameters and convergence speed compared to traditional methods such as standard SSA, genetic algorithm (GA), and particle swarm optimization (PSO); (3) The proposed hybrid model achieves a root mean square error (RMSE) of 0.2136, a mean absolute percentage error (MAPE) of 0.0232, and a Nash efficient (NSE) of 0.9427 for DO prediction, outperforming other similar data-driven models such as IBAS-LSTM and IDA-GRU. The prediction performance of the model meets the practical needs of precise DO prediction in aquaculture.

IntroductionSkin greasiness occurred on stored apples (Malus domestica Borkh.) is generally believed to result from changes in surface wax components. Previous reports have typically correlated wax changes with greasiness scores to reveal the contributing wax components. A notable limitation of this approach is that greasiness scores are highly subjective and influenced by individual perception.MethodsThis study aimed to assess skin quality by quantitatively analyzing wax morphology changes in greasy ‘Jonagold’ apples using Atomic Force Microscopy (AFM) roughness parameters Ra, Rq, Rmax, and Rz, and to correlate these changes with wax composition.ResultsAFM results revealed that wax crystals disappeared as skin greasiness increased, accompanied by significant declines in roughness parameters Ra, Rq, Rmax, and Rz, which decreased by 70% to 85%. Chemical analysis showed a significant increase in liquid esters, including linoleate and oleate esters, in the surface waxes, which negatively correlated with the decline in roughness parameters. Key genes related to ester production, such as MdFAD2, MdWSD1, and MdWBC11, exhibited increased expression and were also negatively correlated with decreases in Rq, Ra and Rz. Additionally, 1-Methylcyclopropene (1-MCP) treatment suppressed both the development of greasiness and the associated changes.DiscussionOur findings suggest that the increased liquid esters contribute to alternations in wax morphology in greasy apples, and that MdFAD2, MdWSD1, and MdWBC11, play crucial roles in ester biosynthesis. These results highlight the effectiveness of AFM roughness parameters Ra, Rq, Rmax, and Rz in quantifying wax morphology changes in apples during skin greasiness development.

Abstract Smart hydrogel sensors, functioning as implantable devices, play a vital role in health monitoring and early warning, overcoming the limitations of conventional clinical methods to achieve direct, continuous, and precise monitoring. Widely employed across various biomedical fields, these sensors offer unique advantages for early health monitoring, ensuring direct, continuous, and highly accurate monitoring. In addition to detecting biomolecules, smart hydrogel sensors, with their flexibility and biocompatibility, monitor disease‐specific markers, offer insights into disease progression, and contribute to the early identification of diseases. This article provides a comprehensive review of the types of hydrogel sensors employed in human health monitoring. The study discusses recent advancements in smart hydrogel sensor research, aiming to offer promising methods for human health monitoring. Finally, the paper outlines prospective research directions for hydrogel sensors in the field of human health monitoring. While further research and clinical validation are essential, hydrogel sensors are poised to play a pivotal role in clinical applications, furnishing people with accurate and continuous health monitoring.

Familial exudative vitreoretinopathy (FEVR) is a severe genetic disorder characterized by incomplete vascularization of the peripheral retina and associated symptoms that can lead to vision loss. However, the underlying genetic causes of approximately 50% of FEVR cases remain unknown. Here, we report two heterozygous variants in calcyphosine-like gene (CAPSL) that is associated with FEVR. Both variants exhibited compromised CAPSL protein expression. Vascular endothelial cell (EC)-specific inactivation of Capsl resulted in delayed radial/vertical vascular progression, compromised endothelial proliferation/migration, recapitulating the human FEVR phenotypes. CAPSL-depleted human retinal microvascular endothelial cells (HRECs) exhibited impaired tube formation, decreased cell proliferation, disrupted cell polarity establishment, and filopodia/lamellipodia formation, as well as disrupted collective cell migration. Transcriptomic and proteomic profiling revealed that CAPSL abolition inhibited the MYC signaling axis, in which the expression of core MYC targeted genes were profoundly decreased. Furthermore, a combined analysis of CAPSL-depleted HRECs and c-MYC-depleted human umbilical vein endothelial cells uncovered similar transcription patterns. Collectively, this study reports a novel FEVR-associated candidate gene, CAPSL, which provides valuable information for genetic counseling of FEVR. This study also reveals that compromised CAPSL function may cause FEVR through MYC axis, shedding light on the potential involvement of MYC signaling in the pathogenesis of FEVR.

The endoplasmic reticulum (ER) membrane protein complex (EMC) is responsible for monitoring the biogenesis and synthetic quality of membrane proteins with tail-anchored or multiple transmembrane domains. The EMC subunit EMC6 is one of the core members of EMC and forms an enclosed hydrophilic vestibule in cooperation with EMC3. Despite studies demonstrating that deletion of EMC3 led to rhodopsin mislocalization in rod photoreceptors of mice, the precise mechanism leading to the failure of rhodopsin trafficking remains unclear. Here, we generated the first rod photoreceptor-specific knockout of Emc6 (RKO) and cone photoreceptor-specific knockout of Emc6 (CKO) mouse models. Deficiency of Emc6 in rod photoreceptors led to progressive shortening of outer segments (OS), impaired visual function, mislocalization and reduced expression of rhodopsin, and increased gliosis in rod photoreceptors. In addition, CKO mice displayed the progressive death of cone photoreceptors and abnormal localization of cone opsin protein. Subsequently, proteomics analysis of the RKO mouse retina illustrated that several cilium-related proteins, particularly anoctamin-2 (ANO2) and transmembrane protein 67 (TMEM67), were significantly down-regulated prior to OS degeneration. Detrimental rod photoreceptor cilia and mislocalized membrane disc proteins were evident in RKO mice. Our data revealed that in addition to monitoring the synthesis of rhodopsin-dominated membrane disc proteins, EMC6 also impacted rod photoreceptors' ciliogenesis by regulating the synthesis of membrane proteins associated with cilia, contributing to the mislocalization of membrane disc proteins.

In the university laboratory environment, it is not uncommon for individual laboratory personnel to be inadequately aware of laboratory safety standards and to fail to wear protective equipment (helmets, goggles, masks) in accordance with the prescribed norms. Manual inspection is costly and prone to leakage, and there is an urgent need to develop an efficient and intelligent detection technology. Video surveillance of laboratory protective equipment reveals that these items possess the characteristics of small targets. In light of this, a laboratory protective equipment recognition method based on the improved YOLOv7 algorithm is proposed. The Global Attention Mechanism (GAM) is introduced into the Efficient Layer Aggregation Network (ELAN) structure to construct an ELAN-G module that takes both global and local features into account. The Normalized Gaussian Wasserstein Distance (NWD) metric is introduced to replace the Complete Intersection over Union (CIoU), which improves the network's ability to detect small targets of protective equipment under experimental complex scenarios. In order to evaluate the robustness of the studied algorithm and to address the current lack of personal protective Equipment (PPE) datasets, a laboratory protective equipment dataset was constructed based on multidimensionality for the detection experiments of the algorithm. The experimental results demonstrated that the improved model achieved a mAP value of 84.2 %, representing a 2.3 % improvement compared to the original model, a 5 % improvement in the detection rate, and a 2 % improvement in the Micro-F1 score. In comparison to the prevailing algorithms, the accuracy of the studied algorithm has been markedly enhanced. The approach addresses the challenge of the challenging detection of small targets of protective equipment in complex scenarios in laboratories, and plays a pivotal role in perfecting laboratory safety management system.

Ginseng, the dried root of Panax ginseng C.A. Mey., is widely used in Chinese herbal medicine. Ginsenosides, the primary active components of ginseng, exhibit diverse anticancer functions through various mechanisms, such as inhibiting tumor cell proliferation, promoting apoptosis, and suppressing cell invasion and migration. In this article, the mechanism of action of 20 ginsenoside subtypes in tumor therapy and the research progress of multifunctional nanosystems are reviewed, in order to provide reference for clinical prevention and treatment of cancer.

ABSTRACT Background In this network meta‐analysis (NMA), the efficiency and safety of PD‐1 inhibitors + chemotherapy and PD‐L1 inhibitors + chemotherapy were compared in the first‐line therapy of patients with extensive‐stage small cell lung cancer (ES‐SCLC). Methods We searched research databases, conference abstracts, and trial registries and subsequently chose relevant studies and extracted dates. The NMA was conducted to estimate the efficiency and safety of the PD‐1 inhibitors + chemotherapy and PD‐L1 inhibitors + chemotherapy on overall survival (OS), progression‐free survival (PFS), overall remission rate (ORR), and adverse events (AEs). Studies were assessed for quality. Subgroup analyses were used to evaluate study heterogeneity. Results We included six randomized trials with a total of 3163 patients. Direct comparisons showed that patients who received either PD‐1 inhibitors + chemotherapy (HR: 0.71, 95% CI: 0.57–0.87) or PD‐L1 inhibitors + chemotherapy (HR: 0.74, 0.61–0.89) demonstrated significantly longer OS than those who received placebo + chemotherapy. The results of the NMA showed that no significant differences in OS (HR 0.96 95% CI: 0.72–1.3), PFS (HR 0.83, 95% CI: 0.51–1.4), and ORR (OR 1.3 95% CI: 0.66–2.5) were observed for PD‐1 inhibitors + chemotherapy compared with PD‐L1 inhibitors + chemotherapy, but the Bayesian ranking revealed that patients receiving PD‐1 inhibitors + chemotherapy tended to have longer OS, PFS benefit, and better treatment response than patients receiving PD‐L1 inhibitors + chemotherapy. In terms of safety, no significant difference was observed in their safety profiles. Conclusion In comparison to placebo + chemotherapy, PD‐L1 inhibitors + chemotherapy and PD‐1 inhibitors + chemotherapy significantly improved survival for ES‐SCLC. According to the available data, PD‐L1 inhibitors + chemotherapy and PD‐1 inhibitors + chemotherapy had equivalent efficacy and safety; however, the level of evidence of this type of comparison is limited.

Sea buckthorn (Hippophae Fructus), as a homologous species of medicine and food, is widely used by Mongolians and Tibetans for its anti-tumor, antioxidant and liver-protecting properties. In this review, the excellent anti-tumor effect of sea buckthorn was first found through network pharmacology, and its active components such as isorhamnetin, quercetin, gallic acid and protocatechuic acid were found to have significant anti-tumor effects. The research progress and application prospect of sea buckthorn and its active components in anti-tumor types, mechanism of action, liver protection, anti-radiation and toxicology were reviewed, providing theoretical basis for the development of sea buckthorn products in the field of anti-tumor research and clinical application.

Intermetallic nanoparticles (i‐NPs) have received considerable attention as high‐performance catalysts for diverse catalytic applications. However, high‐entropy i‐NPs have been rarely reported due to particle growth and phase separation in the multicomponent alloy. In this study, for the first time, an integrated approach of template and structure transformation is introduced to synthesize a series of sub ≈ 5 nm multicomponent i‐NPs with varying compositions. Firstly, ultrathin PtCu nanosheets (NSs) are directly converted into bimetallic PtCu i‐NPs. Furthermore, these PtCu NSs are also used as templates for epitaxial growth of the other metals, followed by annealing to obtain high‐loading, novel compositions and uniform i‐NPs with ternary, quaternary, and quinary compositions, including high‐entropy i‐NPs. Interestingly, L10 intermetallic phases are obtained when Fe is introduced. As a proof‐of‐concept application, these high‐entropy i‐NPs showed superior catalytic performance for the hydrogen evolution reaction , which can be attributed to the negatively shifted d‐band center of Pt, thereby resulting in reduced H* adsorption energy at Pt sites as supported by density functional theory calculations. Overall, this research presents a promising method for the development of i‐NPs with various compositions.

Summary: Podocytopathies, such as focal segmental glomerulosclerosis (FSGS), are characterized by podocyte injury and can easily progress to end-stage kidney disease. However, the mechanisms underlying podocyte injury remain unclear. We observed podocyte injury along with pyroptosis in patients with FSGS. Bioinformatic analysis of public datasets revealed that transmembrane protein 30a (Tmem30a) might be associated with FSGS. The expression of Temem30a and the podocyte-related protein, nephrin, were significantly downregulated in patients with FSGS, adriamycin (ADR)-induced mice, and podocyte-specific Tmem30aloxP/loxP; NPHS2-Cre mice, whereas the expression of NLR family pyrin domain containing 3 (NLRP3) and ASC, two pyroptosis-related proteins, were significantly upregulated. Meanwhile, the pyroptosis inhibitor MCC950 and disulfiram (DSF) increased Tmem30a and podocyte-related proteins expression, and inhibited pyroptosis-related proteins expression in ADR-induced mouse podocytes and Tmem30a knockdown (KD) mouse podocytes. Therefore, Tmem30a might protect against podocyte injury by inhibiting pyroptosis, suggesting a potential therapeutic target for podocytopathies.

Abstract Triple-negative breast cancer (TNBC) is regarded as the deadliest subtype of breast cancer because of its high heterogeneity, aggressiveness, and limited treatment options. Toxoflavin has been reported to possess antitumor activity. In this study, a series of toxoflavin analogs were synthesized, among which D43 displayed a significant dose-dependent inhibitory effect on the proliferation of TNBC cells (MDA-MB-231 and HCC1806). Additionally, D43 inhibited DNA synthesis in TNBC cells, leading to cell cycle arrest at the G2/M phase. Furthermore, D43 consistently promoted intracellular ROS generation, induced DNA damage, and resulted in apoptosis in TNBC cells. These effects could be reversed by N-acetylcysteine. Moreover, D43 significantly inhibited the growth of breast cancer patient-derived organoids and xenografts with a favorable biosafety profile. In conclusion, D43 is a potent anticancer agent that elicits significant antiproliferation, oxidative stress, apoptosis, and DNA damage effects in TNBC cells, and D43 holds promise as a potential candidate for the treatment of TNBC.

Abstract Aim This study aimed to assess the performance of OpenAI’s ChatGPT in generating diagnosis based on chief complaint and cone beam computed tomography (CBCT) radiologic findings. Materials and methods 102 CBCT reports (48 with dental diseases (DD) and 54 with neoplastic/cystic diseases (N/CD)) were collected. ChatGPT was provided with chief complaint and CBCT radiologic findings. Diagnostic outputs from ChatGPT were scored based on five-point Likert scale. For diagnosis accuracy, the scoring was based on the accuracy of chief complaint related diagnosis and chief complaint unrelated diagnoses (1–5 points); for diagnosis completeness, the scoring was based on how many accurate diagnoses included in ChatGPT’s output for one case (1–5 points); for text quality, the scoring was based on how many text errors included in ChatGPT’s output for one case (1–5 points). For 54 N/CD cases, the consistence of the diagnosis generated by ChatGPT with pathological diagnosis was also calculated. The constitution of text errors in ChatGPT’s outputs was evaluated. Results After subjective ratings by expert reviewers on a five-point Likert scale, the final score of diagnosis accuracy, diagnosis completeness and text quality of ChatGPT was 3.7, 4.5 and 4.6 for the 102 cases. For diagnostic accuracy, it performed significantly better on N/CD (3.8/5) compared to DD (3.6/5). For 54 N/CD cases, 21(38.9%) cases have first diagnosis completely consistent with pathological diagnosis. No text errors were observed in 88.7% of all the 390 text items. Conclusion ChatGPT showed potential in generating radiographic diagnosis based on chief complaint and radiologic findings. However, the performance of ChatGPT varied with task complexity, necessitating professional oversight due to a certain error rate.

Abstract Gene therapies provide treatment options for many diseases, but the safe and long-term control of therapeutic transgene expression remains a primary issue for clinical applications. Here, we develop a muscone-induced transgene system packaged into adeno-associated virus (AAV) vectors (AAVMUSE) based on a G protein-coupled murine olfactory receptor (MOR215-1) and a synthetic cAMP-responsive promoter (PCRE). Upon exposure to the trigger, muscone binds to MOR215-1 and activates the cAMP signaling pathway to initiate transgene expression. AAVMUSE enables remote, muscone dose- and exposure-time-dependent control of luciferase expression in the livers or lungs of mice for at least 20 weeks. Moreover, we apply this AAVMUSE to treat two chronic inflammatory diseases: nonalcoholic fatty liver disease (NAFLD) and allergic asthma, showing that inhalation of muscone—after only one injection of AAVMUSE—can achieve long-term controllable expression of therapeutic proteins (ΔhFGF21 or ΔmIL-4). Our odorant-molecule-controlled system can advance gene-based precision therapies for human diseases.

Ensuring the safety of students in higher education institutions during emergencies and their preparedness for them is paramount. This study integrates sustainable development principles into campus safety education to augment students’ emergency response capabilities and their safety awareness. Our study utilizes controlled trials, including safety education interventions and unannounced evacuation drills, as analyzed through data collected from video surveillance, questionnaires, and simulations to evaluate their efficacy. Furthermore, we simulated the evacuation behavior of students in the classroom by combining the emotional contagion of the SIS model with the pedestrian dynamics of the social force model,. The methodology proposed in this article was applied to a real classroom evacuation scenario involving students at a university. The simulation results showed that safety education can significantly reduce students’ evacuation time and enhance their emotional stability during emergencies. Indeed, mobile guides were more effective than fixed guides in calming students’ evacuation panic during the evacuation. Integrating safety education into the sustainable development of campus safety is expected to produce a positive impact on university student evacuations.

Abstract Background The predictive value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) metabolic parameters for predicting AIP relapse is currently unknown. This study firstly explored the value of 18F-FDG PET/CT parameters as predictors of type 1 AIP relapse. Methods This multicenter retrospective cohort study analyzed 51 patients who received 18F-FDG PET/CT prior to treatment and did not receive maintenance therapy after remission. The study collected baseline characteristics and clinical data and conducted qualitative and semi-quantitative analysis of pancreatic lesions and extrapancreatic organs. The study used three thresholds to select the boundaries of pancreatic lesions to evaluate metabolic parameters, including the maximum standard uptake value (SUVmax), mean standard uptake value (SUVmean), total lesion glycolysis (TLG), metabolic tumor volume (MTV), and tumor-to-normal liver standard uptake value ratio (SUVR). Univariate and multivariate analyses were performed to identify independent predictors and build a recurrence prediction model. The model was internally validated using the bootstrap method and a nomogram was created for clinical application. Results In the univariable analysis, the relapsed group showed higher levels of SUVmax (6.0 ± 1.6 vs. 5.2 ± 1.1; P = 0.047), SUVR (2.3 [2.0–3.0] vs. 2.0 [1.6–2.4]; P = 0.026), and TLG2.5 (234.5 ± 149.1 vs. 139.6 ± 102.5; P = 0.020) among the 18F-FDG PET metabolic parameters compared to the non-relapsed group. In the multivariable analysis, serum IgG4 (OR, 1.001; 95% CI, 1.000–1.002; P = 0.014) and TLG2.5 (OR, 1.007; 95% CI, 1.002–1.013; P = 0.012) were independent predictors associated with relapse of type 1 AIP. A receiver-operating characteristic curve of the predictive model with these two predictors demonstrated an area under the curve of 0.806. Conclusion 18F-FDG PET/CT metabolic parameters, particularly TLG2.5, are potential predictors for relapse in patients with type 1 AIP. A multiparameter model that includes IgG4 and TLG2.5 can enhance the ability to predict AIP relapse.

Dockless bike-sharing (DBS) is an effective solution to the “first and last mile” problem in urban transportation. It can be integrated with urban rail transit (URT) to provide passengers with more convenient travel services. This study focuses on the integrated use of DBS and URT in Shenzhen, utilising a multi-buffer zone approach to identify DBS data within URT station catchment areas. By employing ordinary least squares (OLS), geographically weighted regression (GWR) and multiscale geographically weighted regression (MGWR) models, the spatiotemporal heterogeneity of integrated use and its relationship with environmental factors surrounding URT stations were examined. The empirical findings highlight the superiority of the MGWR model in accurately explaining spatial relationships compared to the OLS and GWR models. Furthermore, the study reveals that the impact of built environment factors on integrated use varies during morning and evening peak periods, as well as in terms of access and egress. Specifically, factors such as catering, shopping, companies, residential buildings, bus stops, minor roads, transfer stations and population density were found to influence the integrated use of DBS and URT. These findings not only contribute to the promotion of the DBS-URT integration but also promote the overall development of urban transportation.

Abstract Objective Evidence on the association between the creatinine to body weight (Cre/BW) ratio and the risk of pre-diabetes to diabetes development remains limited. Our study aimed to examine the association between the Cre/BW ratio and incident diabetes in pre-diabetic patients. Methods This retrospective cohort study included 24,506 pre-diabetic participants who underwent health checks from 2010 to 2016 in China. We used the Cox proportional-hazards regression model to explore the relationship between baseline Cre/BW ratio and diabetes risk in pre-diabetes patients. Using a Cox proportional hazards regression with cubic spline function and smooth curve fitting (cubical spline smoothing), we were able to determine the non-linear relationship between them. We also carried out a number of subgroup and sensitivity analyses. Results The age range of the participants included in this study was 20–99 years, with a majority of 16,232 individuals (66.24%) being men. The mean baseline Cre/BW ratio was 1.06 (SD 0.22) umol/L/kg. 2512 (10.25%) participants received a diabetes final diagnosis over a median follow-up period of 2.89 years. After adjusting for covariates, the Cre/BW ratio had a negative association with incident diabetes in participants with pre-diabetes, per umol/L/kg increase in Cre/BM ratio was accompanied by a 55.5% decrease in diabetes risk (HR = 0.445, 95%CI 0.361 to 0.548). The Cre/BW ratio and risk of diabetes had a non-linear connection, with 1.072 umol/L/kg serving as the ratio's inflection point. The HR were 0.294 (95%CI:0.208–0.414) and 0.712 (95%CI:0.492–1.029), respectively, on the left and right sides of the inflection point. The sensitivity analysis demonstrated the robustness of these results. Subgroup analyses indicated that the Cre/BW ratio was strongly associated with the risk of diabetes among participants who were younger than 50 years, as well as among those with diastolic blood pressure (DBP)

The gastrointestinal tract is an important part of the human immune system. The gut microbiome, which constitutes a major component of the gastrointestinal tract, plays a crucial role in maintaining normal physiological functions and influences the development, diagnosis, and immunotherapy of colorectal cancer (CRC). Natural polysaccharides can be extracted from animals, plants, and traditional Chinese medicines. They serve as an essential energy source for the gut microbiome, promoting probiotic proliferation and regulating the intestinal microecological balance. Moreover, polysaccharides exhibit anti-tumor effects due to their immune regulatory functions and low toxicity. This review focuses on discussing these anti-tumor effects in CRC, along with improving gut microbiome dysbiosis and regulating the tumor immune microenvironment, providing evidence for effective therapeutic strategies against CRC.

Background and aim: Diabetes-associated cognitive impairment (DCI) is a prevalent complication of diabetes. However, there is a lack of viable strategies for preventing and treating DCI. This study aims to explore the efficacy of baicalin (Bai) in attenuating DCI and elucidating the underlying mechanisms. Experimental procedure: GK rats fed a high-fat and high-glucose diet were utilized to investigate the therapeutic potential of Bai. Cognitive function was assessed using the Morris water maze and novel object recognition tests. To gain insight into the molecular mechanisms underlying Bai’s neuro-protective effects, co-cultured BV2/HT22 cells were established under high-glucose (HG) stimulation. The modes of action of Bai were subsequently confirmed in vivo using the DCI model in db/db mice. Key results: Bai restored cognitive and spatial memory and attenuated neuron loss, along with reducing expressions of Aβ and phosphorylated Tau protein in diabetic GK rats. At the cellular level, Bai exhibited potent antioxidant and anti-inflammatory effects against HG stimulation. These effects were associated with the upregulation of Nrf2 and supressed Keap1 levels. Consistent with these in vitro findings, similar mechanisms were observed in db/db mice. The significant neuroprotective effects of Bai were abolished when co-administered with ATRA, a Nrf2 blocker, in db/db mice, confirming that KEAP1-Nrf2 signaling pathway was responsible for the observed effect. Conclusions and implications: Bai demonstrates a great therapeutic potential for attenuating DCI. The antioxidant defense and anti-inflammatory actions of Bai were mediated through the KEAP1-Nrf2 axis. These findings advance our understanding of potential treatment approaches for DCI, a common complication associated with diabetes.

Background: Chronic Rhinosinusitis is a common disease in children. The main function of CFTR is to maintain the thickness of the mucous layer on the surface of the nasal mucosa. CFTR disease-causing variant can cause CFTR protein dysfunction and induce or aggravate chronic infection. However, the carrying status of the CFTR variants in the Chinese population is not clear. Objective: To study the frequency and variants of CFTR in Chinese children with CRS and to analyze the CFTR variants and the clinical characteristics and susceptibility to CRS. Methods: Whole Exome Sequencing was performed to analyze the CFTR genes in a total of 106 CRS children from the Chinese mainland area. The CFTR variants, frequency and clinical data were summarized and analyzed. Results: A total of 31 CFTR variants were detected, of which the carrying rate of 7 sites was significantly higher than that of the population database. 88 patients carried more than 2 variants. 37 people carried variants (MAF

Abstract Immunity-and-matrix-regulatory cells (IMRCs) derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix, which could be mass-produced with stable biological properties. Despite resemblance to mesenchymal stem cells (MSCs) in terms of self-renew and tri-lineage differentiation, the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined. Here, we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury. Following injection into the knees of rabbits with meniscal injury, IMRCs enhanced endogenous fibrocartilage regeneration. In the dose-escalating phase I clinical trial (NCT03839238) with eighteen patients recruited, we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting. Furthermore, the effective results of magnetic resonance imaging (MRI) of meniscus repair and knee functional scores suggested that 5 × 107 cells are optimal for meniscus injury treatment. In summary, we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury. Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.

Endoplasmic reticulum (ER) membrane protein complex (EMC) is required for the co-translational insertion of newly synthesized multi-transmembrane proteins. Compromised EMC function in different cell types has been implicated in multiple diseases. Using inducible genetic mouse models, we revealed defects in retinal vascularization upon endothelial cell (EC) specific deletion of Emc1, the largest subunit of EMC. Loss of Emc1 in ECs led to reduced vascular progression and vascular density, diminished tip cell sprouts, and vascular leakage. We then performed an unbiased transcriptomic analysis on human retinal microvascular endothelial cells (HRECs) and revealed a pivotal role of EMC1 in the β-catenin signaling pathway. Further in-vitro and in-vivo experiments proved that loss of EMC1 led to compromised β-catenin signaling activity through reduced expression of Wnt receptor FZD4, which could be restored by lithium chloride (LiCl) treatment. Driven by these findings, we screened genomic DNA samples from familial exudative vitreoretinopathy (FEVR) patients and identified one heterozygous variant in EMC1 that co-segregated with FEVR phenotype in the family. In-vitro expression experiments revealed that this variant allele failed to facilitate the expression of FZD4 on the plasma membrane and activate the β-catenin signaling pathway, which might be a main cause of FEVR. In conclusion, our findings reveal that variants in EMC1 gene cause compromised β-catenin signaling activity, which may be associated with the pathogenesis of FEVR.

Abstract With the popularity of social media, opinion mining has gradually become a popular research field. Among these fields, sentiment analysis mining is an important research direction in the field of opinion mining. It aims to reveal the public's sentiment tendency, and attitude towards specific topics or events by analyzing text data generated by users on online platforms and digital media. However, the large amount of opinion data usually lacks effective annotation, which limits the learning and construction of opinion models. Therefore, focusing on the problem of the scarcity of labeled data in opinion analysis, this paper proposes a mining method for public opinion sentiment analysis based on multi-model fusion transfer learning, that can make full use of the limited labeled data to improve the learning efficiency of sentiment features by integrating the advantages of different models. Additionally, it introduces a transfer learning strategy to enable the models of the target domains to perform better in the absence of labeled data. Furthermore, the attention mechanism is combined to strengthen the acquisition of key features of the emotional colors and improve the accuracy of sentiment analysis. Specifically, the paper uses the ERNIE model to generate dynamic representations of the text word vectors in the dataset. It also uses TextCNN and BiGRU to construct a joint model for extracting local and overall features of the text word vectors. The parameters of the feature layer of the trained model are migrated to the target domain through transfer learning. The attention mechanism is combined with the model to identify the extreme elements of the sentiment. Finally, the local and overall features are fused to achieve comprehensive mining of public opinion and emotional information. This method can effectively improve the accuracy and generalization of public opinion analysis in cases of data scarcity. In the experimental part, the paper conducts comparisons and analyses in eight aspects: word embedding model, model combination, attention mechanism, transfer learning, source domain dataset, target domain dataset, model training, and baseline model. The four indicators, namely accuracy, precision, recall, and F1-measure are used to evaluate the performance of the method. The experiments are thorough and detailed, demonstrating the effective improvement of opinion mining performance.

A novel ε-polylysine (PL)-modified chitosan membrane (TO-CH-PL) was synthesized by a 2,2,6,6-tetramethylpiperidine (TEMPO) oxidation system. Chitosan film (CH) and polyethylene film (PE) were used as control groups. The water vapor permeability, oxygen permeability and mechanical properties were employed to determine the physical properties of membranes. Meanwhile, the physicochemical properties of TO-CH-PL film was characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. Finally, the preservation effect of TO-CH-PL film on chicken was investigated during storage at 10 ℃ for 6 d. The results showed that PL was successfully grafted onto chitosan molecules through TEMPO oxidation system, the obtained TO-CH-PL membrane exhibited higher physical properties than other selected films. Considering the preservation effect of TO-CH-PL film, the results indicated that the increasing rate of TPC, TVB-N and TBARS, as well as the changes of pH and color of chicken could be significantly delayed by applying the TO-CH-PL membrane. It can be concluded the well preservation effect of TO-CH-PL film on chicken samples. Therefore, PL-modified chitosan films can be used as an alternative method to extend the shelf life of chicken during refrigeration.

Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is identified as the cause of coronavirus disease 2019 (COVID-19) pandemic. Acute kidney injury (AKI), one of serious complications of COVID-19 infection, is the leading contributor to renal failure, associating with high mortality of the patients. This study aimed to identify the shared gene signatures and construct the gene regulatory network between COVID-19 and AKI, contributing to exploring the potential pathogenesis. Methods Utilizing the machine learning approach, the candidate gene signatures were derived from the common differentially expressed genes (DEGs) obtained from COVID-19 and AKI. Subsequently, receiver operating characteristic (ROC), consensus clustering and functional enrichment analyses were performed. Finally, protein-protein interaction (PPI) network, transcription factor (TF)-gene interaction, gene-miRNA interaction, and TF-miRNA coregulatory network were systematically undertaken. Results We successfully identified the shared 6 candidate gene signatures (RRM2, EGF, TMEM252, RARRES1, COL6A3, CUBN) between COVID-19 and AKI. ROC analysis showed that the model constructed by 6 gene signatures had a high predictive efficacy in COVID-19 (AUC = 0.965) and AKI (AUC = 0.962) cohorts, which had the potential to be the shared diagnostic biomarkers for COVID-19 and AKI. Additionally, the comprehensive gene regulatory networks, including PPI, TF-gene interaction, gene-miRNA interaction, and TF-miRNA coregulatory networks were displayed utilizing NetworkAnalyst platform. Conclusions This study successfully identified the shared gene signatures and constructed the comprehensive gene regulatory network between COVID-19 and AKI, which contributed to predicting patients’ prognosis and providing new ideas for developing therapeutic targets for COVID-19 and AKI.

Abstract Over the past few decades, exciton-polaritons have attracted substantial research interest due to their half-light-half-matter bosonic nature. Coupling exciton-polaritons with magnetic orders grants access to rich many-body phenomena, but has been limited by the availability of material systems that exhibit simultaneous exciton resonances and magnetic ordering. Here we report magnetically-dressed microcavity exciton-polaritons in the van der Waals antiferromagnetic (AFM) semiconductor CrSBr coupled to a Tamm plasmon microcavity. Using angle-resolved spectroscopy, we reveal an exceptionally high exciton-photon coupling strength, up to 169 meV, demonstrating ultrastrong coupling that persists up to room temperature. By performing temperature-dependent spectroscopy, we show the magnetic nature of the exciton-polaritons in CrSBr microcavity as the magnetic order changes from AFM to paramagnetic. By applying an out-of-plane magnetic field, we achieve effective tuning of the polariton energy while maintaining the ultrastrong exciton-photon coupling strength. We attribute this to the spin canting process that modulates the interlayer exciton interaction.

BackgroundPneumoconiosis is the most serious occupational disease in China, and silicosis accounts for about half of it. Any intervention effect of physical exercise as the key and core of lung rehabilitation training on silicosis is still unclear.ObjectiveTo explore potential intervention effect of physical exercise on silicotic mice.MethodsForty SPF C57BL/6 male mice were randomly divided into four groups, 10 in each group, including a control group, a physical exercise group, a silicosis model group, and a silicosis model + physical exercise intervention group. Silicotic mouse model was established by using 50 μL SiO2 suspension (200 mg·mL−1). A treadmill was used to prepare mice receiving physical exercise at 0° inclination, 12.3 m·min−1, 60 min·d−1, 5 d·week−1 for 4 weeks. Pathological morphology of lung tissues was evaluated after hematoxylin-eosin (HE) staining; deposition of collagen in lung tissues was evaluated after Van Gieson (VG) staining; expression of p-protein kinase R-like endoplasmic reticulum kinase (PERK) was detected by immunofluorescence staining; expressions of cyclin dependent kinase inhibitors (p21) and p-p38 mitogen activated protein kinase (p38) were detected by immunohistochemistry. The protein expressions of endoplasmic reticulum stress signal factors [p-inositol-requiring enzyme-1α (p-IRE-1α), p-PERK, and p-eukaryotic initiation factor-2α (p-eIF-2α)], senescence signal factors (p-p53, p21, and p16), mitogen-activated protein kinase (MAPK) signal factors [p-p38, p-extracellular regulated protein kinases (p-ERK), and p-stress-activated protein kinase (p-JNK)] were detected by Western blotting.ResultsAfter designed acute SiO2 exposure, the images of micro computed tomography (CT) showed high density shadows in lung tissues of the silicotic mice and less shadows in lung tissues of the physical exercise intervention mice. After HE staining, the proportions of silicotic nodule area in lung tissues was (18.67±3.89) % in the silicosis model group, and significantly decreased to (8.78±1.05) % in the silicosis model + physical exercise intervention group (P

Abstract Artificial lights can cause critical microbial biodeterioration of heritage monuments by promoting the outbreak of phototrophic microbiomes when they are used for touristic viewing. Here, with the ultimate aim of providing innovative solutions for the conservation and visiting of such monuments, we conducted a pioneering two-year in situ manipulative experiment to evaluate the impacts of different artificial light wavelengths (i.e., blue, green and red lights compared to white light) on the phototrophic microbiome of a millennial Chinese imperial mausoleum. Our results show that artificial light can shape the ecophysiological features of the phototrophic bacteriome in this monument and reduce its potential for further biodeterioration. In general, Cyanobacteria dominated (42.0% of the total relative abundance) the phototrophic bacteriome of this cultural relic; however, they were also very sensitive to the choice of artificial light. Compared to white light, monochromatic light, especially green light, reduced Cyanobacteria abundances (18.6%) by decreasing photosynthetic pigment abundances (42.9%); decreased the abundances of heterotrophic species belonging to Proteobacteria (4.5%) and the proportion of genes (6.1%) associated with carbon (i.e., carbon fixation), nitrogen (i.e., denitrification), and sulfur (i.e., dissimilatory sulfate reduction) cycling; and further decreased organic acid (10.1–14.1%) production of the phototrophic bacteriome, which is known to be involved in biodeterioration. Taken together, our findings constitute a major advancement in understanding how light wavelengths influence the phototrophic microbiome in cultural relics, and we found that artificial lights with certain wavelengths (e.g., green light) can help long-term conservation while allowing tourism activities.

Smallanthus sonchifolius (Asteraceae), is an important food plant in the world. There is no systematic report on the chloroplast genome of S. sonchifolius. Here we reported its complete chloroplast genome and analyzed the basic characteristics. The chloroplast genome was 152,301 bp in length, had a GC content of 37.55%, and encoded 113 unique genes, including 79 protein-coding genes, 4 ribosomal RNA genes, and 30 transfer RNA genes. Phylogenetic analysis showed that the tribe Millerieae and the tribe Madieae are closely related in the Asteraceae family. In the tribe Millerieae, Smallanthus was more closely related to Guizotia and Sigesbeckia. This chloroplast genome not only enriches the genome information of Smallanthus, but also lays the foundation for understanding the phylogeny within the genus Smallanthus.