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Abstract Background In the management of complex diseases, the strategic adoption of combination therapy has gained considerable prominence. Combination therapy not only holds the potential to enhance treatment efficacy but also to alleviate the side effects caused by excessive use of a single drug. Presently, the exploration of combination therapy encounters significant challenges due to the vast spectrum of potential drug combinations, necessitating the development of efficient screening strategies. Methods In this study, we propose a prediction scoring method that integrates heterogeneous data using a weighted Bayesian method for drug combination prediction. Heterogeneous data refers to different types of data related to drugs, such as chemical, pharmacological, and target profiles. By constructing a multiplex drug similarity network, we formulate new features for drug pairs and propose a novel Bayesian-based integration scheme with the introduction of weights to integrate information from various sources. This method yields support strength scores for drug combinations to assess their potential effectiveness. Results Upon comprehensive comparison with other methods, our method shows superior performance across multiple metrics, including the Area Under the Receiver Operating Characteristic Curve, accuracy, precision, and recall. Furthermore, literature validation shows that many top-ranked drug combinations based on the support strength score, such as goserelin and letrozole, have been experimentally or clinically validated for their effectiveness. Conclusions Our findings have significant clinical and practical implications. This new method enhances the performance of drug combination predictions, enabling effective pre-screening for trials and, thereby, benefiting clinical treatments. Future research should focus on developing new methods for application in various scenarios and for integrating diverse data sources.

Abstract Ischemic stroke is a common cause of mortality and severe disability in human and currently lacks effective treatment. Neuronal activation and neuroinflammation are the major two causes of neuronal damage. However, little is known about the connection of these two phenomena. This study uses middle cerebral artery occlusion mouse model and chemogenetic techniques to study the underlying mechanisms of neuronal excitotoxicity and severe neuroinflammation after ischemic stroke. Chemogenetic inhibition of neuronal activity in ipsilesional M1 alleviates infarct area and neuroinflammation, and improves motor recovery in ischemia mice. This study identifies that ischemic challenge triggers neuron to produce unique small extracellular vesicles (EVs) to aberrantly activate adjacent neurons which enlarge the neuron damage range. Importantly, these EVs also drive microglia activation to exacerbate neuroinflammation. Mechanistically, EVs from ischemia-evoked neuronal activity induce neuronal apoptosis and innate immune responses by transferring higher miR-100-5p to adjacent neuron and microglia. MiR-100-5p can bind to and activate TLR7 through U18U19G20-motif, thereby activating NF-κB pathway. Furthermore, knock-down of miR-100-5p expression improves poststroke outcomes in mice. Taken together, this study suggests that the combination of inhibiting aberrant neuronal activity and the secretion of specific EVs-miRNAs may serve as novel methods for stroke treatment. Graphical Abstract

Abstract Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength (Zn-Prot M) can alleviate heat stress (HS)-induced intestinal barrier function damage of broilers. A completely randomized design was used for comparatively testing the effects of Zn proteinate on HS and non-HS broilers. Under high temperature (HT), a 1 (Control, HT-CON) + 2 (Zn source) × 2 (added Zn level) factorial arrangement of treatments was used. The 2 added Zn sources were Zn-Prot M and Zn sulfate (ZnS), and the 2 added Zn levels were 30 and 60 mg/kg. Under normal temperature (NT), a CON group (NT-CON) and pair-fed group (NT-PF) were included. Results The results showed that HS significantly reduced mRNA and protein expression levels of claudin-1, occludin, junctional adhesion molecule-A (JAMA), zonula occludens-1 (ZO-1) and zinc finger protein A20 (A20) in the jejunum, and HS also remarkably increased serum fluorescein isothiocyanate dextran (FITC-D), endotoxin and interleukin (IL)-1β contents, serum diamine oxidase (DAO) and matrix metalloproteinase (MMP)-2 activities, nuclear factor kappa-B (NF-κB) p65 mRNA expression level, and protein expression levels of NF-κB p65 and MMP-2 in the jejunum. However, dietary supplementation with Zn, especially organic Zn as Zn-Prot M at 60 mg/kg, significantly decreased serum FITC-D, endotoxin and IL-1β contents, serum DAO and MMP-2 activities, NF-κB p65 mRNA expression level, and protein expression levels of NF-κB p65 and MMP-2 in the jejunum of HS broilers, and notably promoted mRNA and protein expression levels of claudin-1, ZO-1 and A20. Conclusions Our results suggest that dietary Zn, especially 60 mg Zn/kg as Zn-Prot M, can alleviate HS-induced intestinal barrier function damage by promoting the expression of TJ proteins possibly via induction of A20-mediated suppression of the NF-κB p65/MMP-2 pathway in the jejunum of HS broilers.

Abstract Development of potent and broad-spectrum antimicrobial peptides (AMPs) could help overcome the antimicrobial resistance crisis. We develop a peptide language-based deep generative framework (deepAMP) for identifying potent, broad-spectrum AMPs. Using deepAMP to reduce antimicrobial resistance and enhance the membrane-disrupting abilities of AMPs, we identify, synthesize, and experimentally test 18 T1-AMP (Tier 1) and 11 T2-AMP (Tier 2) candidates in a two-round design and by employing cross-optimization-validation. More than 90% of the designed AMPs show a better inhibition than penetratin in both Gram-positive (i.e., S. aureus) and Gram-negative bacteria (i.e., K. pneumoniae and P. aeruginosa). T2-9 shows the strongest antibacterial activity, comparable to FDA-approved antibiotics. We show that three AMPs (T1-2, T1-5 and T2-10) significantly reduce resistance to S. aureus compared to ciprofloxacin and are effective against skin wound infection in a female wound mouse model infected with P. aeruginosa. In summary, deepAMP expedites discovery of effective, broad-spectrum AMPs against drug-resistant bacteria.

Abstract Epstein-Barr virus (EBV) related post-transplant lymphoproliferative disorder (EBV-PTLD) is a life-threatening complication after hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT), for which no standard therapeutic means have been developed. Significant increase expression of natural killer group 2 member D ligands (NKG2DLs) was observed on B-lymphoblastoid cells of EBV-PTLD, indicating NKG2DLs as potential therapeutic targets for treatment of EBV-PTLD. In this study, the recombinant constructs of NKG2D CAR and IL-15/IL-15Rα-NKG2D CAR were generated with a retroviral vector and then transduced to human T cells to produce NKG2D CAR-T and IL-15/IL-15Rα-NKG2D CAR-T cells, respectively. B-lymphoblastoid cell lines (B-LCLs) and the xenografted mouse models were established to evaluate the efficacy of these CAR-T cells. IL-15/IL-15Rα-NKG2D CAR-T cells exhibited superior proliferation and antigen-specific cytotoxic effect compared to NKG2D CAR-T, as IL-15/IL-15Rα signaling promoted the expansion of less differentiated central memory T cells (TCM) and increased expression of CD107a and IFN-γ. Moreover, EBV DNA load was dramatically reduced, and 80% B-LCL cells were eliminated by IL-15/IL-15Rα-NKG2D CAR-T cells after co-culturing. In-vivo study confirmed that IL-15/IL-15Rα-NKG2D CAR-T cell therapy significantly enhanced antiviral efficacy in mice, as the serum load of EBV after IL-15/IL-15Rα-NKG2D CAR-T cell infusion was 1500 times lower than the untreated control (P

Abstract Background Aedes albopictus is an important vector for pathogens such as dengue, Zika, and chikungunya viruses. While insecticides is the mainstay for mosquito control, their widespread and excessive use has led to the increased resistance in Ae. albopictus globally. Gut symbiotic bacteria are believed to play a potential role in insect physiology, potentially linking to mosquitoes’ metabolic resistance against insecticides. Methods We investigated the role of symbiotic bacteria in the development of resistance in Ae. albopictus by comparing gut symbiotic bacteria between deltamethrin-sensitive and deltamethrin-resistant populations. Adults were reared from field-collected larvae. Sensitive and resistant mosquitoes were screened using 0.03% and 0.09% deltamethrin, respectively, on the basis of the World Health Organization (WHO) tube bioassay. Sensitive and resistant field-collected larvae were screened using 5 × LC50 (lethal concentration at 50% mortality) and 20 × LC50 concentration of deltamethrin, respectively. Laboratory strain deltamethrin-sensitive adults and larvae were used as controls. The DNA of gut samples from these mosquitoes were extracted using the magnetic bead method. Bacterial 16S rDNA was sequenced using BGISEQ method. We isolated and cultured gut microorganisms from adult and larvae mosquitoes using four different media: Luria Bertani (LB), brain heart infusion (BHI), nutrient agar (NA), and salmonella shigella (SS). Results Sequencing revealed significantly higher gut microbial diversity in field-resistant larvae compared with field-sensitive and laboratory-sensitive larvae (P

Abstract South-to-North Water Diversion Project, a globally renowned engineering feat, aims to address water supply issues. The sediments within reservoirs play a pivotal role in natural ecosystems, not only as habitats for diverse biota but also as repositories of heavy metals, organic matter, and other contaminants. These sediments serve as a critical interface between sediment and water bodies. This comprehensive analysis focused on the spatial patterns of nutrients, organic matter, and heavy metals in the surface layer and profiles of reservoirs, exploring their interconnectedness. Leveraging the integrated pollution index, organic pollution index, potential ecological risk index, and geo-accumulation index, an ecological risk assessment was performed. The key findings are as follows: (i) Along the Middle Route of the South-to-North Diversion Project, the nutrient and organic matter contents in sediments tends to rise with distance from the Danjiangkou Reservoir, with the TN and TC contents increasing by 2.35- and 3.05-fold, respectively. (ii) As the sediment depth increases, the carbon, nitrogen, phosphorus, and organic matter contents exhibit varying degrees of decline, with average decreases of 62.38%, 67.47%, 17.56%, and 41.83% for TN, TC, TP, and OM, respectively. (iii) Among the eight heavy metals, only manganese (Mn) and zinc (Zn) in the Yahekou Reservoir showed moderate pollution levels, according to the geo-accumulation index. The Mn content within the surface sediments of the six reservoirs ranges from 550 to 1837 mg/kg (average, 1019.5 ± 548.3 mg/kg), whereas the Zn content ranges from 89 to 360 mg/kg (average, 156.5 ± 101.6 mg/kg). (vi) Total phosphorus (TP) and total nitrogen (TN) emerged as the primary pollutants in surface sediments. Comprehensive nitrogen and phosphorus pollution assessment revealed that the surface sediment of Danjiangkou Reservoir is mildly polluted, while Baiguishan and Jiangang Reservoirs are moderately polluted, and the rest are heavily contaminated. For the Yahekou and Chaohe Reservoirs, the average pollutant content indicates moderate pollution, while the remaining reservoirs show mild pollution levels. Graphical Abstract

Abstract Background This study investigated the use of urinary exosomal mRNA as a potential biomarker for the early detection of prostate cancer (PCa). Methods Next-generation sequencing was utilized to analyze exosomal RNA from 10 individuals with confirmed PCa and 10 individuals without cancer. Subsequent validation through qRT-PCR in a larger sample of 43 PCa patients and 92 healthy controls revealed distinct mRNA signatures associated with PCa. Results Notably, mRNAs for RAB5B, WWP1, HIST2H2BF, ZFY, MARK2, PASK, RBM10, and NRSN2 showed promise as diagnostic markers, with AUC values between 0.799 and 0.906 and significance p values. Combining RAB5B and WWP1 in an exoRNA diagnostic model outperformed traditional PSA tests, achieving an AUC of 0.923, 81.4% sensitivity, and 89.1% specificity. Conclusions These findings highlight the potential of urinary exosomal mRNA profiling, particularly focusing on RAB5B and WWP1, as a valuable strategy for improving the early detection of PCa.

Abstract A new rapid dual detection method was established to distinguish Bupleurum scorzonerifolium Willd. (BS) and Bupleurum chinense DC. (BC) simultaneously using the proofreading enzyme-mediated probe cleavage coupled with ladder-shape melting temperature isothermal amplification (proofman–LMTIA). The internal transcribed spacer (ITS) sequences of BS and BC were selected as targets for designs of proofman–LMTIA primers and proofman fluorescence probes labeled with FAM or JOE. The reaction temperature optimization, repeatability and reliability assessment, specificity assessment and sensitivity assessment of the proofman–LMTIA performed for dual detection of BS and BC and its application. The results showed that the optimal reaction temperature of the proofman–LMTIA method was at 63℃, which had strongly specificity, repeatability and reliability, as well as sensitivity, and the detection was completed within 20 min with a detection sensitivity of 1 pg/μL. The proofman–LMTIA method realized dual rapid detection of BS and BC, which showed a strong practical value. The 4 kinds were BC, 1 kind was BS, and 2 kinds were counterfeit in the detection of 7 kinds of BS or BC samples from different habitats. Our study successfully established a new approach for dual rapid detection of BS and BC using the proofman–LMTIA, which will provide an effective technique or method for the authenticity detection of authentic Chinese medicinal materials and present a very important practical significance. Graphical Abstract

Abstract Background Chemokine (C-C motif) receptor 8 (CCR8) is a chemokine receptor selectively expressed on tumor-infiltrating regulatory T cells (Tregs). Strong immunosuppression mediated by CCR8+ Tregs observed in breast and lung malignancies suggest for their functional significance in cancer therapy. To date, detailed characterization of tumor-infiltrating CCR8+ Tregs cells in colorectal cancer (CRC) is limited. Methods To study the presence and functional involvement of CCR8+ Tregs in CRC, we analyzed the proportions of CCR8-expressing T cells in different T cell subsets in tumor and adjacent normal tissues and peripheral blood mononuclear cells (PBMCs) from CRC patients by Flow cytometry. Also, we compared the distribution of CCR8+ T cells in malignant tissues and peripheral lymphoid organs from a subcutaneous CRC murine model. Bioinformatic analysis was performed to address the significance of CCR8 expression levels in CRC prognosis, immune regulatory gene expression profiles and potential molecular mechanisms associated with CCR8+ Tregs in CRC tumors. Further, we administrated an anti-CCR8 monoclonal antibody to CT26 tumor-bearing mice and examined the antitumor activity of CCR8-targeted therapy both in vivo and in an ex vivo confirmative model. Results Here, we showed that Tregs was predominantly presented in the tumors of CRC patients (13.4 ± 5.8, p

Abstract Background Autophagy regulation plays vital roles in many cancers. We aimed to investigate the expression, prognostic value, and immune infiltration of autophagy-related genes in hepatocellular carcinoma (HCC) by bioinformatics analysis. Method Human autophagy-related differentially expressed genes (DEGs) between adjacent and HCC tissues were identified. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We also evaluated immune infiltration and the response to tumor-sensitive drugs. Finally, we verified the expression of these proteins in clinical samples by immunohistochemistry (IHC), RNA isolation and real-time reverse transcription polymerase chain reaction (RT‒PCR). Results A total of 57 autophagy-related DEGs were identified. The HUB genes (BIRC5, CDKN2A, SPP1, and IGF1) were related to the diagnosis and prognosis of HCC. The HUB genes were significantly enriched in immune-related pathways. Furthermore, correlation analysis revealed that HUB gene expression was associated with immune infiltration. We identified 35 tumor-sensitive drugs targeting the HUB genes. Finally, by IHC, we discovered that the protein of CDKN2A, BIRC5, and SPP1 were upregulated in HCC tissues, while IGF1 was downregulated in HCC tissues compared with the levels in paracarcinoma tissues; by RT‒PCR, we discovered that the mRNA of CDKN2A, BIRC5, and SPP1 were upregulated in HCC tissues, while the mRNA of IGF1 was downregulated in HCC tissues compared with the levels in paracarcinoma tissues. Conclusion We screened and validated four autophagy-related genes associated with immune infiltration and prognosis in patients with HCC.

Abstract Colorectal carcinogenesis and progression are associated with aberrant alternative splicing, yet its molecular mechanisms remain largely unexplored. Here, we find that Microrchidia family CW-type zinc finger 2 (MORC2) binds to RRM1 domain of RNA binding motif protein 39 (RBM39), and RBM39 interacts with site 1 of pre-CDK5RAP2 exon 32 via its UHM domain, resulting in a splicing switch of cyclin-dependent kinase 5 regulatory subunit associated protein 2 (CDK5RAP2) L to CDK5RAP2 S. CDK5RAP2 S promotes invasion of colorectal cancer cells in vitro and metastasis in vivo. Mechanistically, CDK5RAP2 S specifically recruits the PHD finger protein 8 to promote Slug transcription by removing repressive histone marks at the Slug promoter. Moreover, CDK5RAP2 S, but not CDK5RAP2 L, is essential for the promotion of epithelial-mesenchymal transition induced by MORC2 or RBM39. Importantly, high protein levels of MORC2, RBM39 and Slug are strongly associated with metastasis and poor clinical outcomes of colorectal cancer patients. Taken together, our findings uncover a novel mechanism by which MORC2 promotes colorectal cancer metastasis, through RBM39-mediated pre-CDK5RAP2 alternative splicing and highlight the MORC2/RBM39/CDK5RAP2 axis as a potential therapeutic target for colorectal cancer.

Abstract While protein aggregation’s association with aging and age-related diseases is well-established, the specific proteins involved and whether dissolving them could alleviate aging remain unclear. Our research addresses this gap by uncovering the role of PKM2 aggregates in aging. We find that PKM2 forms aggregates in senescent cells and organs from aged mice, impairing its enzymatic activity and glycolytic flux, thereby driving cells into senescence. Through a rigorous two-step small molecule library screening, we identify two compounds, K35 and its analog K27, capable of dissolving PKM2 aggregates and alleviating senescence. Further experiments show that treatment with K35 and K27 not only alleviate aging-associated signatures but also extend the lifespan of naturally and prematurely aged mice. These findings provide compelling evidence for the involvement of PKM2 aggregates in inducing cellular senescence and aging phenotypes, and suggest that targeting these aggregates could be a promising strategy for anti-aging drug discovery.

Objective To summarize the experience of nursing care of patients with severe alopecia areata treated with topical diphenylcyclopropenone. Methods Seventeen patients with severe alopecia areata treated with topical diphenylcyclopropenone were enrolled. Before the treatment, self-protection was given to the therapist and informed consent was given to the patients. During the treatment, the principles of procedure and drug dosages were strictly followed. After the treatment, WeChat APP was used in the follow-up management of patients. This management included one-to-one evaluation of and consultation on efficacy, adverse reactions, diet and psychology. Results Seventeen patients completed the 16-week treatments, with an effective rate of 58.82%. The adverse reactions were mild and controllable. The therapists did not experience any adverse reactions such as allergic reactions. Conclusion In the treatment of severe alopecia areata with topical diphenylcyclopropenone, appropriate pre-operative preparation and post-operative care can effectively improve the patient's compliance and the therapeutic efficacy.

Abstract Liver regeneration is a complex process involving the crosstalk between parenchymal and non-parenchymal cells, especially macrophages. However, the underlying mechanisms remain incompletely understood. Here, we identify the E3 ubiquitin ligase TRIM26 as a crucial regulator of liver regeneration. Following partial hepatectomy or acute liver injury induced by carbon tetrachloride, Trim26 knockout mice exhibit enhanced hepatocyte proliferation compared to wild-type controls, while adeno-associated virus (AAV)-mediated overexpression of Trim26 reverses the promotional effects. Mechanistically, Trim26 deficiency promotes the recruitment of macrophages to the liver and their polarization towards pro-inflammatory M1 phenotype. These M1 macrophages secrete Wnts, including Wnt2, which subsequently stimulate hepatocyte proliferation through the activation of Wnt/β-catenin signaling. In hepatocytes, Trim26 knockdown reduces the ubiquitination and degradation of β-catenin, thereby further enhancing Wnt/β-catenin signaling. Pharmacological inhibition of Wnt/β-catenin pathway by ICG-001 or depletion of macrophages by clodronate liposomes diminishes the pro-regenerative effects of Trim26 deficiency. Moreover, bone marrow transplantation experiments provide evidence that Trim26 knockout in myeloid cells alone can also promote liver regeneration, highlighting the critical role of macrophage Trim26 in this process. Taken together, our study uncovers TRIM26 as a negative regulator of liver regeneration by modulating macrophage polarization and Wnt/β-catenin signaling in hepatocytes, providing a potential therapeutic target for promoting liver regeneration in clinical settings.

Abstract Background This study explores the medicinal plant knowledge of the Baiku Yao, a unique ethnic group in China. Despite existing research on their ethnobotanical practices, a comprehensive understanding of their medicinal flora remains lacking. This study aims to document and analyze the species distribution, utilization, and traditional knowledge of medicinal plants used by Baiku Yao. Methods Ethnobotanical surveys were conducted in various Baiku Yao villages across different seasons from 2019 to 2023. Informants were interviewed, and plant specimens were collected and identified. Statistical analyses, including the Relative Frequency of Citation (RFC), were employed to understand plant importance in Baiku Yao culture. Results In an ethnobotanical survey conducted in the Baiku Yao region, 434 medicinal plant species were documented, highlighting significant ethnobotanical diversity and a deep cultural integration of traditional medicinal practices. The study revealed pronounced geographical variations in plant knowledge among villages, with a notable reliance on wild plants, as 85.48% were sourced from the wild, reflecting unique local ethnobotanical knowledge. Predominantly herbs and shrubs were used due to their accessibility and abundance in the local environment. High Relative Frequency of Citation (RFC) values for certain species underscored their importance for local health needs and additional economic value. The utilization of various plant parts, particularly whole plants, roots, and leaves, indicates a holistic approach to medicinal applications, adapted to combat prevalent health issues such as skin and infectious diseases. The study also uncovered the Baiku Yao’s cultural practices for countering “Gu” afflictions—a range of pathogenic conditions—with 18 diverse antidote plants used for skin, digestive, and musculoskeletal disorders. The study underscores the imperative of preserving this rich medicinal heritage through innovative models that engage youth and leverage new media, ensuring the inheritance and evolution of Baiku Yao’s traditional knowledge. Conclusions Baiku Yao’s medicinal plant use reflects a deep, culturally ingrained knowledge, closely tied to local ecology. The study highlights the importance of preserving this unique ethnobotanical heritage and suggests interdisciplinary approaches for future research.

This study was conducted to explore the aging technology of high-grade beef, a total of 12 high-grade fattening Angus longissimus dorsi were selected and aged in dry or wet environment for 3, 5 and 7 d, and the meat basic physicochemical indexes, free amino acids and volatile flavor compounds were compared and analyzed. The results showed that the pH of beef with dry-aging for 3 and 5 days was significantly lower than that with wet-aging, the pH of beef with dry-aging for 7 d was significantly higher than that with wet-aging (P

Abstract Background Citrus is a major fruit crop, and RNA-sequencing (RNA-seq) data can be utilized to investigate its gene functions, heredity, evolution, development, and the detection of genes linked to essential traits or resistance to pathogens. However, it is challenging to use the public RNA-seq datasets for researchers without bioinformatics training, and expertise. Results OrangeExpDB is a web-based database that integrates transcriptome data of various Citrus spp., including C. limon (L.) Burm., C. maxima (Burm.) Merr., C. reticulata Blanco, C. sinensis (L.) Osbeck, and Poncirus trifoliata (L.) Raf., downloaded from the NCBI SRA database. It features a blast tool for browsing and searching, enabling quick download of expression matrices for different transcriptome samples. Expression of genes of interest can be easily generated by searching gene IDs or sequence similarity. Expression data in text format can be downloaded and presented as a heatmap, with additional sample information provided at the bottom of the webpage. Conclusions Researchers can utilize OrangeExpDB to facilitate functional genomic analysis and identify key candidate genes, leveraging publicly available citrus RNA-seq datasets. OrangeExpDB can be accessed at http://www.orangeexpdb.com/ .

Abstract Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is an immunoglobulin superfamily protein primarily expressed on epithelial surfaces and myeloid cells. It plays a significant role in cancer progression by inhibiting apoptosis, promoting drug resistance, and facilitating cancer cell invasion and metastasis. Overexpression of CEACAM6 has been observed in various cancers, including lung, breast, colorectal, and hepatocellular cancers, and is associated with poorer overall survival and disease-free survival. Its differential expression on tumor cell surfaces makes it a promising cancer marker. This review aims to provide a comprehensive summary of CEACAM6’s role in different cancer types, its involvement in signaling pathways, and recent advancements in CEACAM6-targeted treatments.

Abstract Although bortezomib (BTZ) is the cornerstone of anti-multiple myeloma (MM) therapy, the inevitable primary and secondary drug resistance still seriously affects the prognosis of patients. New treatment strategies are in need. Sodium-calcium exchanger 1 (NCX1) is a calcium-permeable ion transporter on the membrane, and our previous studies showed that low NCX1 confers inferior viability in MM cells and suppressed osteoclast differentiation. However, the effect of NCX1 on BTZ sensitivity of MM and its possible mechanism remain unclear. In this study, we investigated the effect of NCX1 on BTZ sensitivity in MM, focusing on cellular processes of autophagy and cell viability. Our results provide evidence that NCX1 expression correlates with MM disease progression and low NCX1 expression increases BTZ sensitivity. NCX1/Ca2+ triggered autophagic flux through non-canonical NFκB pathway in MM cells, leading to attenuated the sensitivity of BTZ. Knockdown or inhibition of NCX1 could potentiate the anti-MM activity of BTZ in vitro and vivo, and inhibition of autophagy sensitized NCX1-overexpressing MM cells to BTZ. In general, this work implicates NCX1 as a potential therapeutic target in MM with BTZ resistance and provides novel mechanistic insights into its vital role in combating BTZ resistance.

SRY‐box transcription factor 6 (SOX6) is a member of the SOX gene family and inhibits the proliferation of cervical cancer cells by inducing cell cycle arrest. However, the final cell fate and significance of these cell‐cycle‐arrested cervical cancer cells induced by SOX6 remains unclear. Here, we report that SOX6 inhibits the proliferation of cervical cancer cells by inducing cellular senescence, which is mainly mediated by promoting transforming growth factor beta 2 (TGFB2) gene expression and subsequently activating the TGFβ2–Smad2/3–p53–p21WAF1/CIP1–Rb pathway. SOX6 promotes TGFB2 gene expression through the MAP4K4–MAPK (JNK/ERK/p38)–ATF2 and WT1–ATF2 pathways, which is dependent on its high‐mobility group (HMG) domain. In addition, the SOX6‐induced senescent cervical cancer cells are resistant to cisplatin treatment. ABT‐263 (navitoclax) and ABT‐199 (venetoclax), two classic senolytics, can specifically eliminate the SOX6‐induced senescent cervical cancer cells, and thus significantly improve the chemosensitivity of cisplatin‐resistant cervical cancer cells. This study uncovers that the MAP4K4/WT1–ATF2–TGFβ2 axis mediates SOX6‐induced cellular senescence, which is a promising therapeutic target in improving the chemosensitivity of cervical cancer.

The inclusions, microstructure evolution and impact toughness of the coarse-grained heat-affected zone (CGHAZ) of Al–Ti–Ca deoxidized shipbuilding steel plates with different Al contents after high-heat input welding of 400 kJ cm−1 are investigated. The characteristics of inclusions and their influence on the refinement of microstructure and impact toughness in CGHAZ was elucidated. Increasing the Al content from 0.016 wt% to 0.022 wt% and 0.043 wt% results in an increase in the average size of prior austenite grain and the brittle phase fractions, while decreasing the content of intragranular acicular ferrites (IAFs). The results of the thermodynamic calculations, high-temperature laser scanning confocal microscopy and differential scanning calorimetry all show that increasing the Al content can diminish the austenitic stable region, elevate the transition temperature from austenite to ferrite and suppress the nucleation of IAF. In the present steels, the IAF formation is successfully induced by the specific inclusions, namely Al2O3–CaO–Ti2O3–MnS(-CaS), in which the calcium aluminate inclusions are embedded with Ti-oxides and CaS–MnS precipitates. The effective inclusions have the number density of 93 mm−2 in 16Al steel and 27 mm−2 in 22Al steel, but they are rarely found in 43Al steel. On average, an effective inclusion can induce 3.4 IAFs in 16Al steel and 2.8 IAFs in 22Al steel. Thus, as the Al content increases from 0.016 wt% to 0.22 wt% and 0.043 wt%, the impact toughness of CGHAZ at −40 °C decreases from 134 J to 78 J and 24 J with the welding heat input of 400 kJ cm−1.

ABSTRACT Salmonella enterica serovar Typhimurium (ST) is a predominant serovar causing foodborne illnesses worldwide. Traditional detection methods often face challenges, including the need for specialized equipment, skilled operators, and lengthy procedures. To address these limitations, we developed a rapid, sensitive, and specific ST detection method by integrating loop-mediated isothermal amplification (LAMP) with the clustered regularly interspaced short palindromic repeats and associated protein 12b (CRISPR/Cas12b) system, all within a single tube. Our results indicate that the LAMP–CRISPR/Cas12b reaction can be completed isothermally in under 1 h without requiring specialized instruments. The platform’s limit of detection (LoD) is 12.5 copies per reaction. Additionally, the system demonstrated 100% inclusivity and exclusivity when tested against 30 reference strains, highlighting its specificity. In practical applications, the LoDs for ST in pure nucleic acid and contaminated fecal samples were 2.32 and 23.2 CFU/mL, respectively, with higher sensitivity observed in pure nucleic acid samples. Overall, our findings underscore the potential of the one-tube LAMP–CRISPR/Cas12b platform as a rapid, sensitive, and specific tool for ST detection, particularly in resource-limited settings.IMPORTANCEHere, we have provided a novel one-step method for Salmonella Typhimurium detection in one pot by integrating the LAMP assay with the CRISPR/Cas12b system, offering significant advantages in terms of simplicity, speed, and accuracy.

With the prevalence of sequentially-emerged sublineages including BA.1, BA.2 and BA.5, SARS-CoV-2 Omicron infection has transformed into a regional epidemic disease. As a sublineage of BA.5, the BA.5.2.48 outbroke and evolved into multi-subvariants in China without clearly established virological characteristics. Here, we evaluated the virological characteristics of two isolates of the prevalent BA.5.2.48 subvariant, DY.2 and DY.1.1 (a subvariant of DY.1). Compared to the normal BA.5 spike, the double-mutated DY.1.1 spike demonstrates efficient cleavage, reduced fusogenicity and higher hACE2 binding affinity. BA.5.2.48 demonstrated enhanced airborne transmission capacity than BA.2 in hamsters. The pathogenicity of BA.5.2.48 is greater than BA.2, as revealed in Omicron-lethal H11-K18-hACE2 rodents. In both naïve and convalescent hamsters, DY.1.1 shows stronger fitness than DY.2 in hamster turbinates. Thus regional outbreaking of BA.5.2.48 promotes the multidirectional evolution of its subvariants, gaining either enhanced pathogenicity or a fitness in upper airways which is associated with higher transmission.

Tumorigenesis and metastasis are highly dependent on the interactions between the tumor and the surrounding microenvironment. In 3D matrix, the fibrous structure of the extracellular matrix (ECM) undergoes dynamic remodeling during tumor progression. In particular, during the late stage of tumor development, the fibers become more aggregated and oriented. However, it remains unclear how cancer cells respond to the organizational change of ECM fibers and exhibit distinct morphology and behavior. Here, we used electrospinning technology to fabricate biomimetic ECM with distinct fiber arrangements, which mimic the structural characteristics of normal or tumor tissues and found that aligned and oriented nanofibers induce cytoskeletal rearrangement to promote directed migration of cancer cells. Mechanistically, caveolin-1(Cav-1)-expressing cancer cells grown on aligned fibers exhibit increased integrin β1 internalization and actin polymerization, which promoted stress fiber formation, focal adhesion dynamics and YAP activity, thereby accelerating the directional cell migration. In general, the linear fibrous structure of the ECM provides convenient tracks on which tumor cells can invade and migrate. Moreover, histological data from both mice and patients with tumors indicates that tumor tissue exhibits a greater abundance of isotropic ECM fibers compared to normal tissue. And Cav-1 downregulation can suppress cancer cells muscle invasion through the inhibition of YAP-dependent mechanotransduction. Taken together, our findings revealed the Cav-1 is indispensable for the cellular response to topological change of ECM, and that the Cav-1/YAP axis is an attractive target for inhibiting cancer cell directional migration which induced by linearization of ECM fibers.

Hydrogels formed by self-assembling peptides with low toxicity and high biocompatibility have been widely used in food and biomedical fields. Seafood contains rich protein resources and is also one of the important sources of natural bioactive peptides. The self-assembled peptides in seafood have good functional activity and are very beneficial to human health. In this review, the sequence of seafood self-assembly peptide was introduced, and the preparation, screening, identification and characterization. The rule of self-assembled peptides was elucidated from amino acid sequence composition, amino acid properties (hydrophilic, hydrophobic and electric), secondary structure, interaction and peptide properties (hydrophilic and hydrophobic). It was introduced that the application of hydrogels formed by self-assembled peptides, which lays a theoretical foundation for the development of seafood self-assembled peptides in functional foods and the application of biological materials.

Osteoporosis is a systemic bone disease characterized by reduced bone mass and deterioration of the microstructure of bone tissue, leading to an increased risk of fragility fractures and affecting human health worldwide. Food-derived peptides are widely used in functional foods due to their low toxicity, ease of digestion and absorption, and potential to improve osteoporosis. This review summarized and discussed methods of diagnosing osteoporosis, treatment approaches, specific peptides as alternatives to conventional drugs, and the laboratory preparation and identification methods of peptides. It was found that peptides interacting with RGD (arginine-glycine-aspartic acid)-binding active sites in integrin could alleviate osteoporosis, analyzed the interaction sites between these osteogenic peptides and integrin, and further discussed their effects on improving osteoporosis. These may provide new insights for rapid screening of osteogenic peptides, and provide a theoretical basis for their application in bone materials and functional foods.

Abstract Climate change is exerting unprecedented impacts on marine habitats, and many sessile invertebrate species, such as the endangered giant clam Tridacna maxima, are particularly sensitive to climate driven changes in their environment. Understanding its spatial distribution and conservation requirements is of crucial significance in formulating effective protection strategies. However, the species has been extensively harvested and depleted in many regions, leading to its listing as endangered species by the International Union for Conservation of Nature (IUCN). While marine protected areas (MPAs) are considered effective conservation tools, it remains uncertain whether existing MPAs adequately protect these vulnerable giant clams. To enhance the management and conservation of this species, we employed a Species Distribution Models (SDMs) approach, integrating occurrence records of T. maxima with environmental variables, to predict its potential distribution based on habitat suitability and capture spatiotemporal changes. Based on geographical and genetic variations, the T. maxima in the Indo‐Pacific core region is primarily divided into two populations: the East Indian Ocean‐South China Sea population (EIOS) and the West Pacific‐Indonesia population (WPI). We first quantified realized niche to reveal significant differences in ecological niche space among different populations. Subsequently, SDMs were constructed at both species and population levels, demonstrating that population‐level SDMs provide more reliable predictions of population distributions due to differential responses to climatic predictor variables. Finally, we conducted an assessment to identify conservation gaps for T. maxima beyond the existing MPAs and proposed recommendations for future establishment of MPAs within the current framework. Based on these findings, appropriate conservation policies have been proposed to effectively protect the habitat of different geographical populations of T. maxima. Additionally, spatiotemporal predictions of habitat suitability provide crucial information for developing adaptive management strategies for T. maxima in response to climate change, including designing new protected areas and adjusting the location and extent of existing protected areas based on their geographical distribution.

IntroductionTo investigate the ultrasound characteristics of recurrent laryngeal nerves (RLNs) during radical surgery for thyroid cancer and to enhance the understanding of RLN ultrasound features.MethodsFrom October 2021 to December 2022, a prospective study was conducted involving 24 patients scheduled for bilateral thyroid surgery. Near the conclusion of the surgery, intraoperative ultrasonography of the RLN within the tracheoesophageal groove was performed using a 15-7 MHz transducer. The thickness and width of the RLN were measured during the procedure.ResultsThe internal architecture of the RLN was observed to consist of multiple hypoechoic, parallel, but discontinuous linear hyperechoic areas separated by bands. In the normal RLN group, the diameter of the RLN was relatively consistent, with thickness ranging from 2.20 to 2.71 mm (mean: 2.48 ± 0.14 mm) and width from 1.25 to 1.70 mm (mean: 1.45 ± 0.11 mm). Both weight and the body mass index (BMI) showed a statistically significant correlation with RLN thickness (Weight: r=0.544, P=0.001; BMI: r=0.605, P=0.001). The BMI also showed a statistically significant correlation with the RLN width (r=0.377, P=0.033). In the RLN invasion group, the width of invaded RLNs ranged from 1.9 to 2.3 mm (mean: 2.10 ± 0.11 mm), while the width of non-invaded RLNs ranged from 2.6 to 3.2 mm (mean: 2.93 ± 0.20 mm).ConclusionsUltrasound effectively reveals the structural features of the RLN and enhances sonographers’ understanding of RLN characteristics.

High lead (Pb) levels in agricultural soil and wastewater threaten ecosystems and organism health. Microbial remediation is a cost-effective, efficient, and eco-friendly alternative to traditional physical or chemical methods for Pb remediation. Previous research indicates that micro-organisms employ various strategies to combat Pb pollution, including biosorption, bioprecipitation, biomineralization, and bioaccumulation. This study delves into recent advancements in Pb-remediation techniques utilizing bacteria, fungi, and microalgae, elucidating their detoxification pathways and the factors that influence Pb removal through specific case studies. It investigates how bacteria immobilize Pb by generating nanoparticles that convert dissolved lead (Pb-II) into less harmful forms to mitigate its adverse impacts. Furthermore, the current review explores the molecular-level mechanisms and genetic engineering techniques through which microbes develop resistance to Pb. We outline the challenges and potential avenues for research in microbial remediation of Pb-polluted habitats, exploring the interplay between Pb and micro-organisms and their potential in Pb removal.

Arable soil and crop productivity are severely affected by salinization. Therefore, soil amendments are an important measure for improving saline-alkali soil for agricultural development. Desulfurized gypsum is a common soil amendment that has been used repeatedly alongside organic materials to improve the biological, physical, and chemical properties of saline soil. This study takes the typical saline-alkali farmland soil in Yulin as the research object, and five treatments were established: a blank treatment (CK), a single application 2.5 t ha−1 of desulfurized gypsum (T), 2.5 t ha−1 of desulfurized gypsum and 1.5 t ha−1 of green manure (TL), application 2.5 t ha−1 of desulfurized gypsum and 1.5 t ha−1 of straw (TS), and 2.5 t ha−1 of desulfurized gypsum and 1.5 t ha−1 of organic fertilizer (TV). The results show that the TV treatment achieved a significant improvement in soil nutrients, organic carbon, enzyme activity, and maize yield. In 2022 (2023), the compared of organic matter, TN, TP, TK, AP, and AK increased significantly compared with the CK treatment when the TV treatment was applied. Soil phosphatase activity (SPA), soil urease activity (SUA) and soil sucrase activity (SSA) significantly higher in the TV treatment compared with the other treatments and increased significantly over the two-year period. Furthermore, soil organic carbon (SOC), easily oxidizable organic carbon (EOC), dissolved organic carbon (DOC) and microbial biomass carbon (MBC) also significantly increased with the 2022 and 2023 TV treatments. Correlation analysis revealed a positive relationship between maize yield and soil nutrients, organic carbon, and enzyme activity (P < 0.05). Thus, the TV treatment was determined to be the optimal treatment for soil improvement. This conclusion was supported by analyses performed using membership function analysis, gray correlation analysis, and entropy TOPSIS model evaluation. Therefore, this method increases soil quality, improves soil fertility, achieves high maize yields, and provides a scientific basis for enhancing and utilizing saline-alkali soil in the Loess Plateau.

Background Gastric intestinal metaplasia(GIM) is an independent risk factor for GC, however, its pathogenesis is still unclear. Ferroptosis is a new type of programmed cell death, which may be involved in the process of GIM. The purpose of this study was to analyze the expression of ferroptosis-related genes (FRGs) in GIM tissues and to explore the relationship between ferroptosis and GIM. Method The results of GIM tissue full transcriptome sequencing were downloaded from Gene Expression Omnibus(GEO) database. R software (V4.2.0) and R packages were used for screening and enrichment analysis of differentially expressed genes(DEGs). The key genes were screened by least absolute shrinkage and selection operator(LASSO) and support vector machine-recursive feature elimination(SVM-RFE) algorithm. Receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of key genes in GIM. Clinical samples were used to further validate hub genes. Results A total of 12 differentially expressed ferroptosis-related genes (DEFRGs) were identified. Using two machine learning algorithms, GOT1, ALDH3A2, ACSF2 and SESN2 were identified as key genes. The area under ROC curve (AUC) of GOT1, ALDH3A2, ACSF2 and SESN2 in the training set were 0.906, 0.955, 0.899 and 0.962 respectively, and the AUC in the verification set were 0.776, 0.676, 0.773 and 0.880, respectively. Clinical samples verified the differential expression of GOT1, ACSF2, and SESN2 in GIM. Conclusion We found that there was a significant correlation between ferroptosis and GIM. GOT1, ACSF2 and SESN2 can be used as diagnostic markers to effectively identify GIM.

Abstract During freezing periods, nutrients (carbon and organic matter, etc.) are enriched in the water and sediment of lakes in cold-arid regions, leading to potential algal bloom outbreaks and other health risks to the ecosystem. Particularly, dissolved organic matter (DOM) is a critical component of the nutrients and plays an important role in the global carbon cycle. However, the mechanisms of DOM transfer between ice and water remain unclear. This study analyzed the influence of microbial community on DOM composition using 16 s RNA, 3DEEM, and FT-ICR MS in Daihai Lake and Wuliangsuhai Lake in the Yellow River Basin, China. According to the spectral analysis, the content of endogenous organic matter, such as humus, accounted for 40% of the total DOM in water, while the content of tryptophan and tyrosine accounted for 80% of the total DOM in ice. The results of mass spectrometry showed that lignin was the main component, and the content of organic matter in the ice was less than that in the water. Molecular structures of seven DOM coexisting in the lake ice and water were elucidated with adapted Kendrick-analogous network visualization, which clearly illustrates that long-chain DOM molecules are derived from small molecules, while other heteroatoms are complexed with the side groups. The positive correlations between CHO, CHNO, CHOS, CHOS and Actinomyces indicate that DOM actively interacted with the microbial community. 44% of CHO compounds have the same molecular formula in water, the content of CHOS in the water of the two lakes was closed to 7% higher than that in the ice. Meanwhile, DOM dynamically migrate between ice and water via interstitial water because of the solubility changes under microbial transformation, which has been proved by the decrease in the contents of the humus and tryptophan-like substances in the ice from the bottom to the surface and lower contents of carbohydrate and unsaturated aromatic hydrocarbon in the water than the ice. This study helps to predict the composition and structure of DOM during the migration in lakes and provides a scientific basis for environmental remediation with high concentration of carbon.

Abstract Background Adult neurogenesis occurs in the subventricular zone (SVZ) and the subgranular zone of the dentate gyrus in the hippocampus. The neuronal stem cells in these two neurogenic niches respond differently to various physiological and pathological stimuli. Recently, we have found that the decrement of carboxypeptidase E (CPE) with aging impairs the maturation of brain-derived neurotrophic factor (BDNF) and neurogenesis in the SVZ. However, it remains unknown whether these events occur in the hippocampus, and what the role of CPE is in the adult hippocampal neurogenesis in the context of Alzheimer’s disease (AD). Methods In vivo screening was performed to search for miRNA mimics capable of upregulating CPE expression and promoting neurogenesis in both neurogenic niches. Among these, two agomirs were further assessed for their effects on hippocampal neurogenesis in the context of AD. We also explored whether these two agomirs could ameliorate behavioral symptoms and AD pathology in mice, using direct intracerebroventricular injection or by non-invasive intranasal instillation. Results Restoration of CPE expression in the hippocampus improved BDNF maturation and boosted adult hippocampal neurogenesis. By screening the miRNA mimics targeting the 5’UTR region of Cpe gene, we developed two agomirs that were capable of upregulating CPE expression. The two agomirs significantly rescued adult neurogenesis and cognition, showing multiple beneficial effects against the AD-associated pathologies in APP/PS1 mice. Of note, noninvasive approach via intranasal delivery of these agomirs improved the behavioral and neurocognitive functions of APP/PS1 mice. Conclusions CPE may regulate adult hippocampal neurogenesis via the CPE–BDNF–TrkB signaling pathway. This study supports the prospect of developing miRNA agomirs targeting CPE as biopharmaceuticals to counteract aging- and disease-related neurological decline in human brains.

Abstract With the rapid development of artificial intelligence and data science, Dynamic Bayesian Network (DBN), as an effective probabilistic graphical model, has been widely used in many engineering fields. And swarm intelligence algorithm is an optimization algorithm based on natural selection with the characteristics of distributed, self-organization and robustness. By applying the high-performance swarm intelligence algorithm to DBN structure learning, we can fully utilize the algorithm's global search capability to effectively process time-based data, improve the efficiency of network generation and the accuracy of network structure. This study proposes an improved bacterial foraging optimization algorithm (IBFO-A) to solve the problems of random step size, limited group communication, and the inability to maintain a balance between global and local searching. The IBFO-A algorithm framework comprises four layers. First, population initialization is achieved using a logistics-sine chaotic mapping strategy as the basis for global optimization. Second, the activity strategy of a colony foraging trend is constructed by combining the exploration phase of the Osprey optimization algorithm. Subsequently, the strategy of bacterial colony propagation is improved using a "genetic" approach and the Multi-point crossover operator. Finally, the elimination-dispersal activity strategy is employed to escape the local optimal solution. To solve the problem of complex DBN learning structures due to the introduction of time information, a DBN structure learning method called IBFO-D, which is based on the IBFO-A algorithm framework, is proposed. IBFO-D determines the edge direction of the structure by combining the dynamic K2 scoring function, the designed V-structure orientation rule, and the trend activity strategy. Then, according to the improved reproductive activity strategy, the concept of "survival of the fittest" is applied to the network candidate solution while maintaining species diversity. Finally, the global optimal network structure with the highest score is obtained based on the elimination-dispersal activity strategy. Multiple tests and comparison experiments were conducted on 10 sets of benchmark test functions, two non-temporal and temporal data types, and six data samples of two benchmark 2T-BN networks to evaluate and analyze the optimization performance and structure learning ability of the proposed algorithm under various data types. The experimental results demonstrated that IBFO-A exhibits good convergence, stability, and accuracy, whereas IBFO-D is an effective approach for learning DBN structures from data and has practical value for engineering applications.

The Pan-Eurasian Experiment Modelling Platform (PEEX-MP) is one of the key blocks of the PEEX Research Programme. The PEEX MP has more than 30 models and is directed towards seamless environmental prediction. The main focus area is the Arctic-boreal regions and China. The models used in PEEX-MP cover several main components of the Earth’s system, such as the atmosphere, hydrosphere, pedosphere and biosphere, and resolve the physical-chemical-biological processes at different spatial and temporal scales and resolutions. This paper introduces and discusses PEEX MP multi-scale modelling concept for the Earth system, online integrated, forward/inverse, and socioeconomical modelling, and other approaches with a particular focus on applications in the PEEX geographical domain. The employed high-performance computing facilities, capabilities, and PEEX dataflow for modelling results are described. Several virtual research platforms (PEEX-View, Virtual Research Environment, Web-based Atlas) for handling PEEX modelling and observational results are introduced. The overall approach allows us to understand better physical-chemical-biological processes, Earth’s system interactions and feedbacks and to provide valuable information for assessment studies on evaluating risks, impact, consequences, etc. for population, environment and climate in the PEEX domain. This work was also one of the last projects of Prof. Sergej Zilitinkevich, who passed away on 15 February 2021. Since the finalization took time, the paper was actually submitted in 2023 and we could not argue that the final paper text was agreed with him.

Abstract Background The pathogenesis of vitiligo remains unclear. The genes encoding vitiligo-related RNA-binding proteins (RBPs) and their underlying pathogenic mechanism have not been determined. Results Single-cell transcriptome sequencing (scRNA-seq) data from the CNCB database was obtained to identify distinct cell types and subpopulations and the relative proportion changes in vitiligo and healthy samples. We identified 14 different cell types and 28 cell subpopulations. The proportion of each cell subpopulation significantly differed between the patients with vitiligo and healthy groups. Using RBP genes for unsupervised clustering, we obtained the specific RBP genes of different cell types in vitiligo and healthy groups. The RBP gene expression was highly heterogeneous; there were significant differences in some cell types, such as keratinocytes, Langerhans, and melanocytes, while there were no significant differences in other cells, such as T cells and fibroblasts, in the two groups. The melanocyte-specific RBP genes were enriched in the apoptosis and immune-related pathways in the patients with vitiligo. Combined with the bulk RNA-seq data of melanocytes, key RBP genes related to melanocytes were identified, including eight upregulated RBP genes (CDKN2A, HLA-A, RPL12, RPL29, RPL31, RPS19, RPS21, and RPS28) and one downregulated RBP gene (SLC3A2). Cell experiments were conducted to explore the role of the key RBP gene SLC3A2 in vitiligo. Cell experiments confirmed that melanocyte proliferation decreased, whereas apoptosis increased, after SLC3A2 knockdown. SLC3A2 knockdown in melanocytes also decreased the SOD activity and melanin content; increased the Fe2+, ROS, and MDA content; significantly increased the expression levels of TYR and COX2; and decreased the expression levels of glutathione and GPX4. Conclusion We identified the RBP genes of different cell subsets in patients with vitiligo and confirmed that downregulating SLC3A2 can promote ferroptosis in melanocytes. These findings provide new insights into the pathogenesis of vitiligo.

Abstract Background Home phototherapy (HPT) remains a contentious alternative to inpatient phototherapy (IPT) for neonatal hyperbilirubinemia. To guide evidence-based clinical decision-making, we conducted a meta-analysis of randomized clinical trials (RCTs) and cohort studies and assessed the comparative risks and benefits of HPT and IPT. Methods PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure Database, Wanfang Database, Chinese Science and Technique Journals Database, ClinicalTrials.gov, and International Clinical Trial Registry Platform trial were searched from inception until June 2, 2023. We included RCTs and cohort studies and adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Study quality was assessed with the Cochrane Collaboration Risk of Bias tool and the Newcastle–Ottawa scale. The outcome measures were phototherapy duration, daily bilirubin level reduction, exchange transfusion, hospital readmission, parental stress scale, and complications. We used fixed- or random-effects meta-analysis models, assessed heterogeneity (I 2 ), conducted subgroup analyses, evaluated publication bias, and graded evidence quality. Results Nine studies (998 patients) were included (four RCTs, five cohort studies). HPT was associated with longer phototherapy duration (SMD = 0.55, 95% CI: 0.06–1.04, P = 0.03). Cohort study subgroup analysis yielded consistent results (SMD = 0.90; 95% CI: 0.69 to 1.11, P

In order to develop new packaging materials to extend the shelf life of tuna, LA/ZN antibacterial nanofiber film was prepared by coaxial electrospinning technology with zein (ZN) and leaf aldehyde (LA) as raw materials. The morphology and structure of LA/ZN nanofiber film were analyzed by scanning electron microscope, infrared spectrum and differential scanning calorimetry, and the antibacterial mechanism of the fiber film was explored. The preservation effect of LA/ZN nanofiber film on tuna was investigated. The results indicated that the LA/ZN nanofiber membrane had a linear morphology, smooth surface, and uniformly distributed fiber diameters ranging from 475~575 nm. The encapsulation of LA in corn was a physical process, and there was no chemical interaction between the components in the electrospinning process. After adding LA, the initial melting temperature of the membrane decreased slightly. LA had broad-spectrum antibacterial properties, which could cause damage to bacterial cell walls and membranes, as well as leakage of macromolecular substances such as proteins and DNA, leading to bacterial death. In addition, the results of the 4 ℃ tuna preservation experiment showed that LA/ZN nanofiber film could effectively reduce the total number of fish colonies, volatile base nitrogen content, and histamine content, delay the deterioration of fish texture, and extend the shelf life of tuna fillets by three days. The excellent preservation performance of LA/ZN nanofiber film was expected to be applied in the preservation of aquatic products.

This research was to assess the dietary copper (Cu) requirement of broiler chickens fed a practical corn-soybean meal diet during 22–42 d of age. A total of 288 numbered Arbor Acres male broilers at 22 d of age were randomly allotted 6 treatments with 8 replicate cages (6 broilers per cage) per treatment. Broilers were fed a Cu-unsupplemented corn-soybean meal basal diet (control, containing 7.36 mg Cu/kg) or the basal diet added with 3, 6, 9, 12, or 15 mg Cu/kg from CuSO4·5H2O for 21 d. Quadratic, asymptotic and broken-line models were fitted and the best fitted models were selected to determine dietary Cu requirements. The results revealed that the contents of Cu in serum and liver, mRNA expression levels of Cu- and zinc-containing superoxide dismutase (CuZnSOD) in liver and monoamine oxidase b (MAO B) in heart, as well as protein expression level of CuZnSOD in liver were affected (P

Influenza vaccination is the most cost-effective strategy for influenza prevention. Influenza vaccines have been found to be effective against symptomatic and medically attended outpatient influenza illnesses. However, there is currently a lack of data regarding the effectiveness of inactivated influenza vaccines in Chongqing, China. We conducted a prospective observational test-negative design study. Outpatient and emergency cases presenting with influenza-like illnesses (ILI) and available influenza reverse transcription polymerase chain reaction (RT-PCR) were selected and classified as cases (positive influenza RT-PCR) or controls (negative influenza RT-PCR). A total of 7,307 cases of influenza and 7,905 control subjects were included in this study. The overall adjusted influenza vaccine effectiveness (IVE) was 44.4% (95% confidence interval (CI): 32.5–54.2%). In the age groups of less than 6 years old, 6–18 years old, and 19–59 years old, the adjusted IVE were 32.2% (95% CI: 10.0–48.9%), 48.2% (95% CI: 30.6–61.4%), and 72.0% (95% CI: 43.6–86.1%). The adjusted IVE for H1N1, H3N2 and B (Victoria) were 71.1% (95% CI: 55.4–81.3%), 36.1% (95% CI: 14.6–52.2%) and 33.7% (95% CI: 14.6–48.5%). Influenza vaccination was effective in Chongqing from 2018 to 2022. Evaluating IVE in this area is feasible and should be conducted annually in the future.

ABSTRACTChina’s massive urbanisation development will undoubtedly serve as a global reference. Due to the uncertainty of statistical data, nighttime light (NTL) data have emerged as alternative data for urbanisation evaluation. Here, the application of the Prolonged Artificial NTL Dataset of China (1984–2020) has been newly expanded. Total-value statistical, complex NTL index (CNLI), NTL concentration degree, rank-size rule, and Markov transfer matrix were used to systematically mine information about urban change from multiple perspectives. China’s urbanisation exhibited rapid growth and outwards expansion. The total percentage increase in NTL brightness and NTL area was 409.38% and 302.58%, respectively. The Yangtze River Delta urban agglomeration of East China had the fastest urbanisation (CNLI Trend = 0.0057/a, p 95%) in city size type transition. The spatiotemporal changes in NTL obtained were of great significance for monitoring urban expansion patterns, making government decisions, and quantifying China’s sustainable development.

ABSTRACTCyberspace is a dynamic and complex environment that poses unique challenges in understanding and managing its intricacies. In this study, we developed a framework for ‘Geo-Cyber’ spatial correlation mapping and expression, leveraging geographical information to enhance the understanding of cyberspace. The theory of geographic metaphor is incorporated into the framework to provide a comprehensive and intuitive approach for comprehending the interplay between geographic space and cyberspace. The framework enables the modeling and visual expression of geo-cyber correlations using a layered knowledge-graph representation. To graphically represent the complex knowledge graph within cyberspace, the framework uses an ‘Object-VirtualObject-Process-Decision’ layered modeling approach, which facilitates effective navigation and comprehension of the inherent cyberspace dynamics. Based on the experimental data, we employed a virtual geo-cyber environment system to demonstrate the effectiveness of the framework. The application cases include resource navigation and situational awareness in cyberspace to showcase the practicality and relevance of the proposed framework. The analysis indicated that the framework enhances situational awareness, facilitates effective decision-making, and promotes a holistic comprehension of the interplay between geography and cyberspace by leveraging geographic information and incorporating metaphorical cognition, layered modeling, and visualization techniques.

AbstractBackground A growing body of research supports the important role of the TH2 axis in alopecia areata (AA). Dupilumab is a humanized monoclonal antibody against IL-4Rα that downregulates TH2 response. Although efficacy has been shown in clinical trials, real-world data on the use of dupilumab in AA patients is limited.Objectives To report on a case series of 10 patients with AA who were treated with dupilumab and provide real-world evidence regarding its efficacy in treating severe AA.Methods In this retrospective single-center study, all AA patients treated with dupilumab treatment were included between May 2022 and October 2023. Clinical outcome measures (Severity of Alopecia Tool, SALT) and adverse events (AEs) were analyzed. In addition, a literature review was conducted to summarize the efficacy of AA with dupilumab and the characteristics of patients previously reported in the literature.Results We identified 10 patients with AA who were or are being treated with dupilumab, with a median (range) treatment duration of 8 (3-15) months. Of these, four patients have high serum immunoglobulin E (IgE) levels (≥200IU/ml). The mean (IQR) pretreatment SALT score was 79% (52-100). Seven of 10 patients achieved at least 50% re-growth. Of those who improved, the mean (IQR) percentage change in SALT score at 3 months and the end of follow-up was 57% (29%-89%) and 95% (68-100), respectively. Notably, seven patients (70%) had white hair regrowth, with the white hair slowly decreasing over time and the proportion of pigmented black hair increasing. Dupilumab was well tolerated by all patients. No adverse events were reported.Conclusions Overall, our research supports dupilumab as another candidate that possesses potential benefits for AA. High levels of IgE may be not prerequisites for dupilumab’s successful treatment response.

The grey wolf optimizer is a widely used parametric optimization algorithm. It is affected by the structure and rank of grey wolves and is prone to falling into the local optimum. In this study, we propose a grey wolf optimizer for fusion cell-like P systems. Cell-like P systems can parallelize computation and communicate from cell membrane to cell membrane, which can help the grey wolf optimizer jump out of the local optimum. Design new convergence factors and use different convergence factors in other cell membranes to balance the overall exploration and utilization capabilities of the algorithm. At the same time, dynamic weights are introduced to accelerate the convergence speed of the algorithm. Experiments are performed on 24 test functions to verify their global optimization performance. Meanwhile, a support vector machine model optimized by the grey wolf optimizer for fusion cell-like P systems has been developed and tested on six benchmark datasets. Finally, the optimizing ability of grey wolf optimizer for fusion cell-like P systems on constrained optimization problems is verified on three real engineering design problems. Compared with other algorithms, grey wolf optimizer for fusion cell-like P systems obtains higher accuracy and faster convergence speed on the test function, and at the same time, it can find a better parameter set stably for the optimization of support vector machine parameters, in addition to being more competitive on constrained engineering design problems. The results show that grey wolf optimizer for fusion cell-like P systems improves the searching ability of the population, has a better ability to jump out of the local optimum, has a faster convergence speed, and has better stability.

Growing teratoma syndrome (GTS) is a rare condition that arises secondary to malignant germ cell tumors. It is characterized by an enlarging abdominal mass during or after chemotherapy, normal tumor markers, and histopathological indications of mature teratoma components. Awareness of GTS is limited, and it is often mistaken for disease progression or recurrence. This misdiagnosis can lead to delayed treatment and increased risk of complications. Therefore, early identification of GTS is crucial to avoid unnecessary systemic treatments and reduce financial burden. GTS is unresponsive to chemotherapy or radiotherapy and complete surgical resection is the sole therapeutic strategy. In this report, we present a case of GTS in a 20-year-old female following treatment for immature teratoma, alongside a review of the relevant literature aimed at enriching our insight into the clinical manifestations of GTS.

ABSTRACT Hepatitis B virus (HBV), a common blood transmission pathogen worldwide, can lead to viral hepatitis, cirrhosis, liver cancer, and other liver diseases. In particular, occult hepatitis B virus infection (OBI) may be caused by an immune response leading to suppressed virus replication. Gut microbiota can change the immunity status of the human body and, therefore, affect the replication of HBV. Thus, to identify whether there are differences in gut microbiota between HBV carriers and OBI carriers, we collected fecal samples from 18 HBV carriers, 24 OBI blood donors, and also 20 healthy blood donors as negative control. After 16S sequencing, we found that the abundance of Faecalibacterium was significantly reduced in samples from OBI blood donors compared with those from healthy blood donors. Compared with samples from HBV carriers, the samples from OBI blood donors had a significantly increased abundance of Subdoligranulum, which might stimulate immune activation, thus inhibiting HBV replication and contributing to the formation of occult infection. Our findings revealed the potential role of gut microbiota in the formation of OBI and further provided a novel strategy for the treatment of HBV infection.IMPORTANCEOccult hepatitis B virus infection (OBI) is a special form of hepatitis B virus infection with hepatitis B surface antigen (HBsAg) positive and hepatitis B virus (HBV) DNA negative. Gut microbiota may contribute to the immune response leading to suppressed virus replication and, thus, participates in the development of OBI. The study on gut microbiota of OBI blood donors provides novel data considerably advancing our understanding of the immune mechanism for the determination of occult hepatitis B virus infection, which is helpful for improving the strategy of the treatment of HBV infection.

Summary: The emergence of SARS-CoV-2 variants raises concerns about the efficacy of existing COVID-19 vaccines and therapeutics. Previously, we identified a conserved cryptic class 5 epitope of SARS-CoV-2 receptor binding domain (RBD) by two cross-neutralizing antibodies 7D6 and 6D6. Intriguingly, this site remains resistant to substantial mutations occurred in ever-changing SARS-CoV-2 subvariants. As compared to class 3 antibody S309, 6D6 maintains broad and consistent neutralizing activities against SARS-CoV-2 variants. Furthermore, 6D6 effectively protected hamster from the virulent Beta strain. Sequence alignment of approximately 6 million documented SARS-CoV-2 isolates revealed that 6D6 epitope maintains an exceptionally high conservation rate (99.92%). Structural analysis demonstrated that all 33 mutations accumulated in XBB.1.5 since the original strain do not perturb the binding 6D6 to RBD, in line with the sequence analysis throughout the antigenicity evolution of SARS-CoV-2. These findings suggest the potential of this epitope serving as a critical determinant for vaccines and therapeutic design.