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The sensorimotor cortex participates in diverse functions with different reciprocally connected subregions and projection-defined pyramidal neuron types therein, while the fundamental organizational logic of its circuit elements at the single-cell level is still largely unclear. Here, using mouse Cre driver lines and high-resolution whole-brain imaging to selectively trace the axons and dendrites of cortical pyramidal tract (PT) and intratelencephalic (IT) neurons, we reconstructed the complete morphology of 1,023 pyramidal neurons and generated a projectome of 6 subregions within the sensorimotor cortex. Our morphological data revealed substantial hierarchical and layer differences in the axonal innervation patterns of pyramidal neurons. We found that neurons located in the medial motor cortex had more diverse projection patterns than those in the lateral motor and sensory cortices. The morphological characteristics of IT neurons in layer 5 were more complex than those in layer 2/3. Furthermore, the soma location and morphological characteristics of individual neurons exhibited topographic correspondence. Different subregions and layers were composed of different proportions of projection subtypes that innervate downstream areas differentially. While the axonal terminals of PT neuronal population in each cortical subregion were distributed in specific subdomains of the superior colliculus (SC) and zona incerta (ZI), single neurons selectively innervated a combination of these projection targets. Overall, our data provide a comprehensive list of projection types of pyramidal neurons in the sensorimotor cortex and begin to unveil the organizational principle of these projection types in different subregions and layers., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Mei Yao et al.)

Homeostatic plasticity maintains the stability of functional brain networks. The axon initial segment (AIS), where action potentials start, undergoes dynamic adjustment to exert powerful control over neuronal firing properties in response to network activity changes. However, it is poorly understood whether this plasticity involves direct synaptic input to the AIS. Here, we show that changes of GABAergic synaptic input from chandelier cells (ChCs) drive homeostatic tuning of the AIS of principal neurons (PNs) in the prelimbic (PL) region, while those from parvalbumin-positive basket cells do not. This tuning is evident in AIS morphology, voltage-gated sodium channel expression, and PN excitability. Moreover, the impact of this homeostatic plasticity can be reflected in animal behavior. Social behavior, inversely linked to PL PN activity, shows time-dependent alterations tightly coupled to changes in AIS plasticity and PN excitability. Thus, AIS-originated homeostatic plasticity in PNs may counteract deficits elicited by imbalanced ChC presynaptic input at cellular and behavioral levels.

Despite the great potential of starving therapy caused by nanoreactor based on glucose oxidase (GOX) in tumor therapy, efficiency and uncontrolled reaction rates in vivo lead to inevitable toxicity to normal tissues, which seriously hindering their clinical conversion. Herein, a cascade nanoreactor (GOX/Mn/MPDA) was constructed by coating mesoporous polydopamine nanoparticles (MPDA) with MnO 2 shell and then depositing GOX into honeycomb-shaped manganese oxide nanostructures to achieve a combination of ferroptosis, photothermal therapy and starving therapy. Upon uptake of nanodrugs to cancer cells, the MnO 2 shell would deplete glutathione (GSH) and produce Mn 2+ , while a large amount of H 2 O 2 generated from the catalytic oxidation of glucose by GOX would accelerate the Fenton-like reaction mediated by Mn 2+ , producing high toxic •OH. More importantly, the cascade reaction between GOX and MnO 2 would be further strengthened by localized hyperthermia caused by irradiated by near-infrared laser (NIR), inducing significant anti-tumor effects in vitro and in vivo. Regarding the effectiveness of tumor treatment in vivo, the tumor inhibition rate achieved an impressive 64.33%. This study provided a new strategy for anti-tumor therapeutic by designing a photothermal-enhanced cascade catalytic nanoreactor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Axo-axonic cells (AACs), also called chandelier cells (ChCs) in the cerebral cortex, are the most distinctive type of GABAergic interneurons described in the neocortex, hippocampus, and basolateral amygdala (BLA). AACs selectively innervate glutamatergic projection neurons (PNs) at their axon initial segment (AIS), thus may exert decisive control over PN spiking and regulate PN functional ensembles. However, the brain-wide distribution, synaptic connectivity, and circuit function of AACs remain poorly understood, largely due to the lack of specific and reliable experimental tools. Here, we have established an intersectional genetic strategy that achieves specific and comprehensive targeting of AACs throughout the mouse brain based on their lineage ( Nkx2.1 ) and molecular ( Unc5b , Pthlh ) markers. We discovered that AACs are deployed across essentially all the pallium-derived brain structures, including not only the dorsal pallium-derived neocortex and medial pallium-derived hippocampal formation, but also the lateral pallium-derived claustrum-insular complex, and the ventral pallium-derived extended amygdaloid complex and olfactory centers. AACs are also abundant in anterior olfactory nucleus, taenia tecta, and lateral septum. AACs show characteristic variations in density across neocortical areas and layers and across subregions of the hippocampal formation. Neocortical AACs comprise multiple laminar subtypes with distinct dendritic and axonal arborization patterns. Retrograde monosynaptic tracing from AACs across neocortical, hippocampal, and BLA regions reveal shared as well as distinct patterns of synaptic input. Specific and comprehensive targeting of AACs facilitates the study of their developmental genetic program and circuit function across brain structures, providing a ground truth platform for understanding the conservation and variation of a bona fide cell type across brain regions and species., Competing Interests: RR, GK, SK, JH, WG, SZ, AP, YQ, BL, ZH No competing interests declared, (© 2024, Raudales et al.)

26% of the world's population lacks access to clean drinking water; clean water and sanitation are major global challenges highlighted by the UN Sustainable Development Goals, indicating water security in public water systems is at stake today. Water monitoring using precise instruments by skilled operators is one of the most promising solutions. Despite decades of research, the professionalism-convenience trade-off when monitoring ubiquitous metal ions remains the major challenge for public water safety. Thus, to overcome these disadvantages, an easy-to-use and highly sensitive visual method is desirable. Herein, an innovative strategy for one-to-nine metal detection is proposed, in which a novel thiourea spectroscopic probe with high 9-metal affinity is synthesized, acting as "one", and is detected based on the 9 metal-thiourea complexes within portable spectrometers in the public water field; this is accomplished by nonspecialized personnel as is also required. During the processing of multimetal analysis, issues arise due to signal overlap and reproducibility problems, leading to constrained sensitivity. In this innovative endeavor, machine learning (ML) algorithms were employed to extract key features from the composite spectral signature, addressing multipeak overlap, and completing the detection within 30-300 s, thus achieving a detection limit of 0.01 mg/L and meeting established conventional water quality standards. This method provides a convenient approach for public drinking water safety testing.

Background: Hepatic hemangioma is the most common type of benign mesenchymal liver tumor and often has a good prognosis. However, giant hepatic hemangioma larger than 10 cm is an unusual event, and accompanying symptoms of internal hemorrhagic necrosis are extremely rare. There are only a few cases reported., Case Summary: Herein, we report the case of a 52-year-old man with hemorrhagic necrosis of a giant hepatic hemangioma. The patient presented to the Department of Hepatobiliary Surgery with a complaint of distending pain on the right abdomen. The patient underwent hepatic artery embolization for giant hepatic hemangioma 2 weeks before presentation. During hospitalization, abdominal computed tomography revealed a mass (15.8 × 14.2 × 14.7 cm) with high density below the right lobe of the liver. The patient subsequently underwent irregular right hepatectomy with the guidance of three-dimensional visualization technology. The surgical anatomy confirmed the diagnosis of internal hemorrhagic necrosis. There was no recurrence or complications in a 4-month follow-up. Previous cases were reviewed to characterize the clinical features of giant hepatic hemangioma with internal hemorrhage necrosis., Conclusion: Cases of giant hepatic hemangioma with internal hemorrhagic necrosis are rare and usually only exhibit fever or epigastric pain. All patients in reviewed cases finally underwent surgical resection. Under these circumstances, the healing effect of transhepatic arterial treatment is not very satisfactory. Patients are deemed poor laparoscopic surgical candidates due to limited abdominal cavity. In order to standardize the diagnosis of these rare cares, the aggregation of existing and future case data is certainly warranted. If diagnosed, consideration should be given to implementing surgical resection according to patients' condition by three-dimensional visualized technology., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Psoriasis is an immune-mediated, chronic, relapsing, inflammatory, systemic disease induced by individual-environmental interactions, and is often lifelong because of the difficulty of treatment. In recent years, a variety of targeted therapies, including biologics, have improved the lesions and quality of life of most psoriasis patients, but they still do not address the problem of relapse and may be associated with decreased efficacy or adverse events such as infections over time. Therefore, there is an urgent need for breakthroughs in psoriasis treatment and in relapse-delaying and non-pharmacologic strategies, and stem cell therapy for psoriasis has emerged. In recent years, research on stem cell therapy for psoriasis has received a lot of attention, however, there is no reference standard as well as consensus in this field of research. Therefore, according to the latest consensus and guidelines, combined with relevant literature reports, clinical practice experience and the results of discussions with experts, this consensus specifies the types of stem cells commonly used in the treatment of psoriasis, the methods, dosages, and routes of stem cell therapy for psoriasis, as well as the clinical evaluations (efficacy and safety) of stem cell therapy for psoriasis. In addition, this consensus also provides normative standards for the processes of collection, preparation, preservation and quality control of stem cells and their related products, as well as recommendations for the management of stem cells during infusion for the treatment of psoriasis. This consensus provides the latest specific reference standards and practice guidelines for the field of stem cell therapy for psoriasis.

Objective: To investigate the macular morphological and visual outcomes of combined idiopathic epiretinal membrane (iERM) removal with triamcinolone acetonide (TA) injection based on consideration of the ectopic inner foveal layer (EIFL) staging scheme., Methods: Retrospective case-control study. The clinical data of 84 eyes of 84 patients who underwent vitrectomy for iERM between 2018 and 2022 were reviewed. The enrolled subjects were divided into the TA and non-TA groups. Fifty-one eyes received intravitreal TA injection following vitrectomy and ERM peeling (TA group), and 33 were only treated by standard vitrectomy and ERM peeling (non-TA group). Preoperative and postoperative EIFL stages, central foveal thickness (CFT), and best-corrected visual acuity (BCVA) were compared between both groups., Results: After a mean follow-up of 7.69 ± 3.68 months, both groups exhibited significant improvement in EIFL stages (P < 0.01), with no discernible advantage observed in the TA group. The TA and non-TA groups demonstrated improvement in the EIFL stages in 56.86 and 63.64% of eyes, respectively (P = 0.43). The CFT and BCVA significantly improved in both groups at the final visit (P < 0.01). However, CFT in the non-TA group displayed a more significant reduction during the follow-up (P < 0.03). Subgroup analysis revealed no significant differences in postoperative CFT and BCVA between the two groups in cases with or without continuous EIFL (P > 0.10)., Conclusion: Our findings indicate that combined intravitreal TA injection following ERM removal conferred no significant benefits in alleviating macular thickening or improving visual acuity in iERM., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: Triple-negative breast cancer (TNBC) poses a significant challenge for treatment efficacy. CD8+ T cells, which are pivotal immune cells, can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing technology. By leveraging these genes, our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to immunotherapy., Methods: Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC databases. In the initial stage, we identified 67 differentially expressed genes associated with immune response in CD8+ T cells. Subsequently, we narrowed our focus to three key genes, namely CXCL13 , GBP2 , and GZMB , which were used to construct a prognostic model. The accuracy of the model was assessed using the validation set data and receiver operating characteristic (ROC) curves. Furthermore, we employed various methods, including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, immune infiltration, and correlation analyses with CD274 (PD-L1) to explore the model's predictive efficacy in immunotherapeutic responses. Additionally, we investigated the potential underlying biological pathways that contribute to divergent treatment responses., Results: We successfully developed a model capable of predicting the prognosis of patients with TNBC. The areas under the curve (AUC) values for the 1-, 3-, and 5-year survival predictions were 0.618, 0.652, and 0.826, respectively. Employing this risk model, we stratified the samples into high- and low-risk groups. Through KEGG enrichment analysis, we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism, whereas the low-risk group demonstrated significant enrichment in cytokine pathways. Furthermore, immune landscape analysis revealed noteworthy variations between (PD-L1) expression and risk scores, indicating that our model effectively predicted the response of patients to immune-based treatments., Conclusion: Our study demonstrates the potential of CXCL13, GBP2, and GZMB as prognostic indicators of clinical outcomes and immunotherapy responses in patients with TNBC. These findings provide valuable insights and novel avenues for developing immunotherapeutic approaches targeting TNBC., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding Chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The aim of this study is to investigate the effect of double-tract reconstruction on short-term clinical outcome, quality of life and nutritional status of patients after proximal gastrectomy by comparing with esophagogastrostomy and total gastrectomy with Roux-en-Y reconstruction., Methods: The clinical data of patients who underwent double tract reconstruction (DTR), esophagogastrostomy (EG), total gastrectomy with Roux-en-Y reconstruction (TG-RY) were retrospectively collected from May 2020 to May 2022. The clinical characteristics, short-term surgical outcomes, postoperative quality of life and nutritional status were compared among the three groups., Results: Compared with the DTR group, the operation time in the TG group was significantly shorter (200(180,240) minutes vs. 230(210,255) minutes, p < 0.01), and more lymph nodes were removed (28(22, 25) vs. 22(19.31), p < 0.01), there were no significant differences in intraoperative blood loss, first flatus time, postoperative hospital stay and postoperative complication rate among the three groups. Postoperative digestive tract angiography was completed in 36 patients in the DTR group, of which 21 (58.3%) showed double-tract type of food passing. The incidence of postoperative reflux symptoms was 9.2% in the DTR group, 43.8% in the EG group and 23.2% in the TG group, repectively (P < 0.01). EORTCQLQ-STO22 questionnaire survey showed that compared with EG group, DTR group had fewer reflux symptoms (P < 0.05), fewer anxiety symptoms (P < 0.05) and more swallowing symptoms (P < 0.05). Compared with TG group, DTR group had fewer reflux symptoms (P < 0.05). There were no other significant differences between the two groups. Compared with TG group and EG group, DTR can better maintain postoperative BMI, and there is no statistical difference between the three groups in terms of hemoglobin and albumin., Conclusions: Although partial double-tract reconstruction approach does not always ensure food to enter the distal jejunum along the two pathways as expected, it still shows satisfactory anti-reflux effect. Moreover, it might improve patients' quality of life and maintain better nutritional status comparing with gastroesophageal anastomosis and total gastrectomy with Roux-en-Y reconstruction., (© 2024. The Author(s).)

Addressing the pervasive issue of bacteria and biofilm infections is crucial in the development of advanced antifouling wound dressings. In this study, a novel wound healing treatment using sulfobetaine (SBMA) decorated electrospun fibrous membrane based on polycaprolactone (PCL)/nitric oxide (NO) donors was developed. The fabrication involved a dual strategy, first integrating NO donors into mesoporous polydopamine (MPDA) and complexed with PCL/PEI to electrospin nanofibers. The fibrous membrane exhibited a potent antibacterial response upon irradiation at 808 nm, owing to a combination of NO and photothermal effect that effectively targets bacteria and disrupts biofilms. Surface functionalization of the membrane with PEI allowed for the attachment of SBMA via Michael addition, fabricating a zwitterionic surface, which significantly hinders protein adsorption and reduces biofilm formation on the wound dressing. In vitro and in vivo assessments confirmed the rapid bactericidal capabilities and its efficacy in biofilm eradication. Combining photothermal activity, targeted NO release and antifouling surface, this multifaceted wound dressing addresses key challenges in bacterial infection management and biofilm eradication, promoting efficient wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Arsenic (As)-contaminated soil poses great health risk to human mostly through inadvertent oral exposure. We investigated CaAl-layered double hydroxide (CaAl-LDH), a promising immobilising agent, for the remediation of As-contaminated Chinese soils. The effects on specific soil properties and As fractionation were analyzed, and changes in the health risk of soil As were accurately assessed by means of advanced in vivo mice model and in vitro PBET-SHIME model. Results showed that the application of CaAl-LDH significantly increased soil pH and concentration of Fe and Al oxides, and effectively converted active As fractions into the most stable residual fraction, guaranteeing long-term remediation stability. Based on in vivo test, As relative bioavailability was significantly reduced by 37.75%. Based on in vitro test, As bioaccessibility in small intestinal and colon phases was significantly reduced by 25.65% and 28.57%, respectively. Furthermore, As metabolism (reduction and methylation) by the gut microbiota inhabiting colon was clearly observed. After immobilisation with CaAl-LDH, the concentration of bioaccessible As(Ⅴ) in the colon fluid was significantly reduced by 61.91%, and organic As (least toxic MMA(V) and DMA(V)) became the main species, which further reduced the health risk of soil As. In summary, CaAl-LDH proved to be a feasible option for immobilisation remediation of As-contaminated soils, and considerable progress was made in relevant health risk assessment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Non-small-cell lung cancer (NSCLC), a common malignant tumor, requires deeper pathogenesis investigation. Autophagy is an evolutionarily conserved lysosomal degradation process that is frequently blocked during cancer progression. It is an urgent need to determine the novel autophagy-associated regulators in NSCLC. Here, we found that pirin was upregulated in NSCLC, and its expression was positively correlated with poor prognosis. Overexpression of pirin inhibited autophagy and promoted NSCLC proliferation. We then performed data-independent acquisition-based quantitative proteomics to identify the differentially expressed proteins (DEPs) in pirin-overexpression (OE) or pirin-knockdown (KD) cells. Among the pirin-regulated DEPs, ornithine decarboxylase 1 (ODC1) was downregulated in pirin-KD cells while upregulated along with pirin overexpression. ODC1 depletion reversed the pirin-induced autophagy inhibition and pro-proliferation effect in A549 and H460 cells. Immunohistochemistry showed that ODC1 was highly expressed in NSCLC cancer tissues and positively related with pirin. Notably, NSCLC patients with pirin high /ODC1 high had a higher risk in terms of overall survival. In summary, we identified pirin and ODC1 as a novel cluster of prognostic biomarkers for NSCLC and highlighted the potential oncogenic role of the pirin/ODC1/autophagy axis in this cancer type. Targeting this pathway represents a possible therapeutic approach to treat NSCLC.

Background: Tertiary lymphoid structures (TLSs) affect the prognosis and efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC), but the underlying mechanisms are not well understood., Methods: TLSs were identified and categorized online from the Cancer Digital Slide Archive (CDSA). Overall survival (OS) and disease-free survival (DFS) were analyzed. GSE111414 and GSE136961 datasets were downloaded from the GEO database. GSVA, GO and KEGG were used to explore the signaling pathways. Immune cell infiltration was analyzed by xCell, ssGSEA and MCP-counter. The analysis of WGCNA, Lasso and multivariate cox regression were conducted to develop a gene risk score model based on the SU2C-MARK cohort., Results: TLS-positive was a protective factor for OS according to multivariate cox regression analysis (p = 0.029). Both the TLS-positive and TLS-mature groups exhibited genes enrichment in immune activation pathways. The TLS-mature group showed more activated dendritic cell infiltration than the TLS-immature group. We screened TLS-related genes using WGCNA. Lasso and multivariate cox regression analysis were used to construct a five-genes (RGS8, RUF4, HLA-DQB2, THEMIS, and TRBV12-5) risk score model, the progression free survival (PFS) and OS of patients in the low-risk group were markedly superior to those in the high-risk group (p < 0.0001; p = 0.0015, respectively). Calibration and ROC curves indicated that the combined model with gene risk score and clinical features could predict the PFS of patients who have received immunotherapy more accurately than a single clinical factor., Conclusions: Our data suggested a pivotal role of TLSs formation in survival outcome and immunotherapy response of NSCLC patients. Tumors with mature TLS formation showed more activated immune microenvironment. In addition, the model constructed by TLS-related genes could predict the response to immunotherapy and is meaningful for clinical decision-making., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown., Methods: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy. Fecal samples were collected at baseline, early on-treatment, response and progression status and were subjected to metagenomic next-generation sequencing and ultra-high-performance liquid chromatography-mass spectrometry analyses to assess the effects of gut microbiota and metabolites on immunotherapy efficacy., Results: The clinical data of 74 advanced EGFR + NSCLC patients were complete and 18 patients' fecal samples were dynamically collected. Patients that used antibiotics had shorter progression-free survival (PFS) (mPFS, 4.8 vs. 6.7 months; P = 0.037); probiotics had no impact on PFS. Two dynamic types of gut microbiota during immunotherapy were identified: one type showed the lowest relative abundance at the response time point, whereas the other type showed the highest abundance at the response time point. Metabolomics revealed significant differences in metabolites distribution between responders and non-responders. Deoxycholic acid, glycerol, and quinolinic acid were enriched in responders, whereas L-citrulline was enriched in non-responders. There was a significant correlation between gut microbiota and metabolites., Conclusions: The use of antibiotics weakens immunotherapy efficacy in patients with advanced EGFR + NSCLC. The distribution characteristics and dynamic changes of gut microbiota and metabolites may indicate the efficacy of immunotherapy in advanced EGFR + NSCLC., (© 2024. The Author(s).)

Part of human long noncoding RNAs (lncRNAs) has been elucidated to play an essential role in the carcinogenesis and progression of hepatocellular carcinoma (HCC), a type of malignant tumor with poor outcomes. Tumor-derived exosomes harboring lncRNAs have also been implicated as crucial mediators to orchestrate biological functions among neighbor tumor cells. The recruitment of tumor-associated macrophages (TAMs) exerting M2-like phenotype usually indicates the poor prognosis. Yet, the precise involvement of tumor-derived lncRNAs in cross-talk with environmental macrophages has not been fully identified. In this study, we reported the aberrantly overexpressed HCC upregulated EZH2-associated lncRNA (HEIH) in tumor tissues and cell lines was positively correlated with poor prognosis, as well as enriched exosomal HEIH levels in blood plasma and cell supernatants. Besides, HCC cell-derived exosomes transported HEIH into macrophages for triggering macrophage M2 polarization, thereby in turn promoting the proliferation, migration, and invasion of HCC cells. Mechanistically, HEIH acted as a miRNA sponge for miR-98-5p to up-regulate STAT3, which was then further verified in the tumor xenograft models. Collectively, our study provides the evidence for recognizing tumor-derived exosomal lncRNA HEIH as a novel regulatory function through targeting miR-98-5p/STAT3 axis in environmental macrophages, which may shed light on the complicated tumor microenvironment among tumor and immune cells for HCC treatment., (© 2024 Wiley Periodicals LLC.)

Introduction: EGFR C797X (C797S or C797G) mutation is the most frequent on-target mechanism of resistance to osimertinib. The hypothesis that the allelic context of C797X/T790M has implications for treatment is on the basis of sporadic reports and needs validation with larger cohorts., Methods: We identified patients with EGFR C797X-mutant NSCLC from nine centers who progressed on osimertinib, all analyzed in a single laboratory through next-generation sequencing. We analyzed genomic profiles and assessed associations between clinical outcomes and C797X status., Results: A total of 365 EGFR C797X-mutant cases were categorized into four subtypes on the basis of allelic context: in cis (75.3%), in trans (6.4%), cis&trans (10.4%), and C797X-only (7.9%). Genomically, the cis&trans subtype displayed the highest frequency of concurrent alterations at osimertinib resistance sites (21.1%), while the in cis subtype had the lowest (8.4%). Clinically, cis&trans patients exhibited the worst progression-free survival (PFS) on both previous (median 7.7 mo) and subsequent treatment (median 1.0 mo) and overall survival (median 3.9 mo). In subsequent treatments, in cis patients exhibited superior PFS with combined brigatinib and cetuximab (median 11.0 mo) compared with other regimens (p = 0.005), while in trans patients exhibited variable outcomes with combined first or second- and third-generation EGFR inhibitor (PFS range: 0.7-8.1 mo, median 2.6 mo). Notably, subtype switching was observed after subsequent treatments, predominantly toward the in cis subtype., Conclusions: Allelic context could define four EGFR C797X-mutant NSCLC subtypes with heterogeneous genetic landscapes and distinct clinical outcomes. Subsequent treatments further complicate the scenario through subtype switching., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Electromagnetic interference (EMI) shielding and infrared stealth technologies are essential for military and civilian applications. However, it remains a significant challenge to integrate various functions efficiently into a material efficiently. Herein, a minimalist strategy to fabricate multifunctional phase change organohydrogels (PCOHs) was proposed, which were fabricated from polyacrylamide (PAM) organohydrogels, MXene/PEDOT:PSS hybrid fillers, and sodium sulfate decahydrate (Na 2 SO 4 ·10H 2 O, SSD) via one-step photoinitiation strategies. PCOHs with a high enthalpy value (130.7 J/g) and encapsulation rate (98%) could adjust the temperature by triggering a phase change of SSD, which can hide infrared radiation to achieve medium-low temperature infrared stealth. In addition, the PCOH-based sensor has good strain sensing ability due to the incorporation of MXene/PEDOT:PSS and can precisely monitor human movement. Remarkably, benefiting from the electron conduction of the three-dimensional conductive network and the ion conduction of the hydrogel, the EMI shielding efficiency ( k ) of PCOHs can reach 99.99% even the filler content as low as 1.8 wt %. Additionally, EMI shielding, infrared stealth, and sensing-integrated PCOHs can be adhered to arbitrary targets due to their excellent flexibility and adaptability. This work offers a promising pathway for fabricating multifunctional phase change materials, which show great application prospects in military and civilian fields.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. The poor prognosis of this malignancy is attributed mainly to the persistent activation of cancer signaling for metastasis. Here, we showed that protein tyrosine phosphatase-like A domain containing 1 (PTPLAD1) is down-regulated in highly metastatic CRC cells and negatively associated with poor survival of CRC patients. Systematic analysis reveals that epithelial-to-mesenchymal transition (EMT) and mitochondrial fusion-to-fission (MFT) transition are two critical features for CRC patients with low expression of PTPLAD1. PTPLAD1 overexpression suppresses the metastasis of CRC in vivo and in vitro by inhibiting the Raf/ERK signaling-mediated EMT and mitofission. Mechanically, PTPLAD1 binds with PHB via its middle fragment (141-178 amino acids) and induces dephosphorylation of PHB-Y259 to disrupt the interaction of PHB-Raf, resulting in the inactivation of Raf/ERK signaling. Our results unveil a novel mechanism in which Raf/ERK signaling activated in metastatic CRC induces EMT and mitochondrial fission simultaneously, which can be suppressed by PTPLAD1. This finding may provide a new paradigm for developing more effective treatment strategies for CRC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Achieving circularly polarized organic ultralong room-temperature phosphorescence (CP-OURTP) with a high luminescent dissymmetry factor (g lum ) is crucial for diverse optoelectronic applications. In particular, dynamically controlling the dissymmetry factor of CP-OURTP can profoundly advance these applications, but it is still unprecedented. This study introduces an effective strategy to achieve photoirradiation-driven chirality regulation in a bilayered structure film, which consists of a layer of soft helical superstructure incorporated with a light-driven molecular motor and a layer of room-temperature phosphorescent (RTP) polymer. The prepared bilayered film exhibits CP-OURTP with an emission lifetime of 805 ms and a g lum value up to 1.38. Remarkably, the g lum value of the resulting CP-OURTP film can be reversibly controlled between 0.6 and 1.38 over 20 cycles by light irradiation, representing the first example of dynamically controlling the g lum in CP-OURTP., (© 2024 Wiley-VCH GmbH.)

In this study, new fluorite high-entropy oxide (HEO), (BiZrMoWCeLa)O 2 , nanoparticles were produced using a surfactant-assisted hydrothermal technique followed by calcination and were used as novel catalytic materials for vanadium redox flow batteries (VRFBs). The HEO calcined at 750 °C (HEO-750) demonstrates superior electrocatalytic activity toward V 3+ /V 2+ and VO 2+ /VO 2 + redox couples compared to those of cells assembled with other samples. The charge-discharge tests further confirm that VRFBs using the HEO-750 catalyst demonstrate excellent Coulombic efficiency, voltage efficiency, and energy efficiency of 97.22, 87.47, and 85.04% at a current density of 80 mA cm -2 and 98.10, 74.76, and 73.34% at a higher current density of 160 mA cm -2 , respectively. Moreover, with 500 charge-discharge cycles, there is no discernible degradation. These results are attributed to the calcination heat treatment, which induces the formation of a new single-phase fluorite structure, which facilitates the redox reactions of the vanadium redox couples. Furthermore, a high surface area, wettability, and plenty of oxygen vacancies can give more surface electroactive sites, improving the electrochemical performance, the charge transfer of the redox processes, and the stability of the VRFBs' electrode. This is the first report on the development of fluorite structure HEO nanoparticles in VRFBs, and it opens the door to further research into other HEOs.

Background: This study aimed to identify metabolic subtypes in ESCA, explore their relationship with immune landscapes, and establish a metabolic index for accurate prognosis assessment., Methods: Clinical, SNP, and RNA-seq data were collected from 80 ESCA patients from the TCGA database and RNA-seq data from the GSE19417 dataset. Metabolic genes associated with overall survival (OS) and progression-free survival (PFS) were selected, and k-means clustering was performed. Immune-related pathways, immune infiltration, and response to immunotherapy were predicted using bioinformatic algorithms. Weighted gene co-expression network analysis (WGCNA) was conducted to identify metabolic genes associated with co-expression modules. Lastly, cell culture and functional analysis were performed using patient tissue samples and ESCA cell lines to verify the identified genes and their roles., Results: Molecular subtypes were identified based on the expression profiles of metabolic genes, and univariate survival analysis revealed 163 metabolic genes associated with ESCA prognosis. Consensus clustering analysis classified ESCA samples into three distinct subtypes, with MC1 showing the poorest prognosis and MC3 having the best prognosis. The subtypes also exhibited significant differences in immune cell infiltration, with MC3 showing the highest scores. Additionally, the MC3 subtype demonstrated the poorest response to immunotherapy, while the MC1 subtype was the most sensitive. WGCNA analysis identified gene modules associated with the metabolic index, with SLC5A1, NT5DC4, and MTHFD2 emerging as prognostic markers. Gene and protein expression analysis validated the upregulation of MTHFD2 in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA., Conclusion: The established metabolic index and identified metabolic genes offer potential for prognostic assessment and personalized therapeutic interventions for ESCA, underscoring the importance of targeting metabolism-immune interactions in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA., (© 2024. The Author(s).)

Surface electroactive sites for tungstate zirconia (WZ) were created by utilizing tungstate-immobilized UiO-66 as precursors via a double-solvent impregnation method under a mild calcination temperature. The WZ-22-650 catalyst, containing a moderate W content (22%), demonstrated a high density of surface electroactive sites. Proper heat treatment facilitated the binding of oligomeric tungsten clusters to stabilized tetragonal ZrO 2 , resulting in improved catalytic performance toward the VO 2+ /VO 2 + redox couples compared to other tested samples. The substantial surface area, mesoporous structure, and establishment of new W-O-Zr bonds affirm the firm anchoring of WO x to ZrO 2 . This robust attachment enhances surface electroactive sites, elevating the electrochemical performance of vanadium redox flow batteries (VRFBs). Charge-discharge tests further demonstrate that the superior voltage efficiency (VE) and energy efficiency (EE) for VRFBs using the WZ-22-650 catalyst are 87.76 and 83.94% at 80 mA cm -2 , which are 13.42% VE and 10.88% EE better than heat-treated graphite felt, respectively. Even at a higher current density of 160 mA cm -2 , VRFBs utilizing the WZ-22-650 catalyst maintained considerable efficiency, recording VE and EE values of 76.76 and 74.86%, respectively. This facile synthesis method resulted in WZ catalysts displaying superior catalytic activity and excellent cyclability, offering a promising avenue for the development of metal-oxide-based catalysts.

Objective: To investigate the association between hyperuricemia and the risk for stroke occurrence, as well as the mediating effect of hypertension on this association. Methods: In this study, the China Chronic Diseases and Nutrition Surveillance system in 2015 was used as baseline data. We identified hospital admissions for stroke using the electronic homepage of inpatient medical records from 2013-2020, and death data were obtained from the 2015-2020 National Mortality Surveillance System. A retrospective cohort was established after matching and linking the database. The Cox proportional hazard regression model was used to analyze the relationship between hyperuricemia and the risk of stroke and its subtypes. Restricted cubic spline analysis was conducted to examine the dose-response relationship between serum uric acid levels and the risk for stroke. Mediation analysis was performed to investigate the mediating effect of hypertension on the association between hyperuricemia and the risk for stroke and its subtypes. Subgroup analyses were conducted based on gender and age groups. Results: A total of 124 352 study subjects were included, with an accumulative follow-up time of 612 911.36 person-years. During the follow-up period, 4 638 cases of stroke were found, including 3 919 cases of ischemic stroke and 689 cases of hemorrhagic stroke. The incidence density of stroke was 756.72 per 100 000 person-years, 641.37 per 100 000 person-years for ischemic stroke, and 114.60 per 100 000 person-years for hemorrhagic stroke. Multivariable Cox proportional hazards regression models showed that after adjusting for covariates, compared to those without hyperuricemia, individuals with hyperuricemia had a 16% higher risk for stroke [hazard ratio ( HR )=1.16, 95% CI : 1.06-1.27], a 12% higher risk of ischemic stroke ( HR =1.12, 95% CI : 1.01-1.24), and a 39% higher risk of hemorrhagic stroke ( HR =1.39, 95% CI : 1.11-1.75). Mediation analysis showed that hypertension partially mediated the associations between hyperuricemia and the risk for stroke, ischemic stroke, and hemorrhagic stroke, with mediation proportions of 36.07%, 39.98%, and 25.34%, respectively. The mediating effect is pronounced in the male population and individuals below 65. Conclusion: Hyperuricemia is a risk factor for stroke, and hypertension partially mediates the effect of hyperuricemia on stroke.

Based on the typical city survey data and statistics of Guangdong Province， a 2018-based 3 km×3 km gridded greenhouse gas emissions inventory was developed for Guangdong Province using the combination of top-down and bottom-up emission factor methods. The inventory covered the CO 2 ， CH 4， and N 2 O emissions from energy， industrial processes， agriculture， land use change and forest， waste management， and indirect sources. The results showed that estimates for CO 2 ， CH 4 ， and N 2 O in Guangdong Province for the year 2018 were 8.5×10 8 ， 1.9×10 6 ， and 1.1×10 5 t， respectively， and 8.5×10 8 ， 4.0×10 7 ， and 3.4×10 7 t by equivalent carbon dioxide， totaling 9.2×10 8 t. CO 2 was the main greenhouse gas in Guangdong Province， accounting for 92.0% of the total emissions. Energy and indirect sources were the main emission sources， accounting for 77.9% and 7.6%， respectively， totaling 85.5%. Spatial distributions illustrated that most grids were greenhouse gas emissions， whereas some others were greenhouse gas sinks； the greenhouse gas emissions were distributed mainly in the Pearl River Delta region and had certain characteristics of distribution along the road network and channels. The greenhouse gas grids of high emission were mainly the locations of high energy-consuming enterprises such as large power plants， steel mills， and cement plants.

Near infrared energy remains untapped toward the maneuvering of entire solar spectrum harvesting for fulfilling the nuts and bolts of solar hydrogen production. We report the use of Au@Cu 7 S 4 yolk@shell nanocrystals as dual-plasmonic photocatalysts to achieve remarkable hydrogen production under visible and near infrared illumination. Ultrafast spectroscopic data reveal the prevalence of long-lived charge separation states for Au@Cu 7 S 4 under both visible and near infrared excitation. Combined with the advantageous features of yolk@shell nanostructures, Au@Cu 7 S 4 achieves a peak quantum yield of 9.4% at 500 nm and a record-breaking quantum yield of 7.3% at 2200 nm for hydrogen production in the absence of additional co-catalysts. The design of a sustainable visible- and near infrared-responsive photocatalytic system is expected to inspire further widespread applications in solar fuel generation. In this work, the feasibility of exploiting the localized surface plasmon resonance property of self-doped, nonstoichiometric semiconductor nanocrystals for the realization of wide-spectrum-driven photocatalysis is highlighted., (© 2024. The Author(s).)

Rhabdias kafunata (Rhabditida: Rhabdiasidae) is a parasitic nematode that significantly affects bufonids. To better understand the genome-level characteristics of related species, Illumina sequencing was used to identify mitochondrial genes and analyze their basic characteristics and gene arrangements. The mitogenome of R. kafunata is 14,068 bp in length and contains 36 genes, including 12 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes and one noncoding region (NCR). The nucleotide composition is highly biased toward A + T, accounting for 75.5% of the entire mitochondrial genome. The cox1 sequence is relatively conserved in Ka/Ks analyses and can be used as a gene fragment for species identification. While 8 of the 12 PCGs use the typical ATN initiation codon, nad1-2, nad4, and cox3 utilize a TTG initiation codon. Most stop codons end with the standard TAA or TAG, except for cytb, which ends with an incomplete TA. Additionally, trnM, trnK, and trnI have the typical clover-leaf secondary structure, while the remaining tRNAs lack the DHU arm or TΨC arm. Phylogenetic analysis indicates that R. kafunata belongs to the Rhabditidae family and is closely related to Litoditis marina and Caenorhabditis angaria among sequenced lepidopteran mitochondrial genomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personalrelationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

In contemporary biomedical research, the accurate automatic detection of cells within intricate microscopic imagery stands as a cornerstone for scientific advancement. Leveraging state-of-the-art deep learning techniques, this study introduces a novel amalgamation of Fuzzy Automatic Contrast Enhancement (FACE) and the You Only Look Once (YOLO) framework to address this critical challenge of automatic cell detection. Yeast cells, representing a vital component of the fungi family, hold profound significance in elucidating the intricacies of eukaryotic cells and human biology. The proposed methodology introduces a paradigm shift in cell detection by optimizing image contrast through optimal fuzzy clustering within the FACE approach. This advancement mitigates the shortcomings of conventional contrast enhancement techniques, minimizing artifacts and suboptimal outcomes. Further enhancing contrast, a universal contrast enhancement variable is ingeniously introduced, enriching image clarity with automatic precision. Experimental validation encompasses a diverse range of yeast cell images subjected to rigorous quantitative assessment via Root-Mean-Square Contrast and Root-Mean-Square Deviation (RMSD). Comparative analyses against conventional enhancement methods showcase the superior performance of the FACE-enhanced images. Notably, the integration of the innovative You Only Look Once (YOLOv5) facilitates automatic cell detection within a finely partitioned grid system. This leads to the development of two models-one operating on pristine raw images, the other harnessing the enriched landscape of FACE-enhanced imagery. Strikingly, the FACE enhancement achieves exceptional accuracy in automatic yeast cell detection by YOLOv5 across both raw and enhanced images. Comprehensive performance evaluations encompassing tenfold accuracy assessments and confidence scoring substantiate the robustness of the FACE-YOLO model. Notably, the integration of FACE-enhanced images serves as a catalyst, significantly elevating the performance of YOLOv5 detection. Complementing these efforts, OpenCV lends computational acumen to delineate precise yeast cell contours and coordinates, augmenting the precision of cell detection., (© 2023. Springer Nature Limited.)

Didymocarpussubpalmatinervis W.T.Wang was shown to be conspecific with Petrocodonlithophilus Y.M.Shui, W.H.Chen & Mich.Möller, by checking original literature, examining specimens, tracing specimen collecting history, and conducting field surveys. The results show morphological characteristics and geographical distribution overlaps between these two species. The transfer of Didymocarpussubpalmatinervis to Petrocodon as a new combination with Petrocodonsubpalmatinervis (W.T.Wang) F.Wen & Z.L.Li is proposed here, and P.lithophilus is synonymized with P.subpalmatinervis . Color photographs and essential information are also provided, including a detailed comparison of description, distribution, habitat, and the proposed IUCN conservation status., Competing Interests: The authors have declared that no competing interests exist., (Zheng-Long Li, Zhang-Jie Huang, Da-Wei Chen, Xin Hong, Fang Wen.)

This study aims to discern the possible molecular mechanism of the effect of ubiquitin-specific peptidase 18 (USP18) on the resistance to BRAF inhibitor vemurafenib in BRAF V600E mutant melanoma by regulating cyclic GMP-AMP synthase (cGAS). The cancer tissues of BRAF V600E mutant melanoma patients before and after vemurafenib treatment were collected, in which the protein expression of USP18 and cGAS was determined. A BRAF V600E mutant human melanoma cell line (A2058R) resistant to vemurafenib was constructed with its viability, apoptosis, and autophagy detected following overexpression and depletion assays of USP18 and cGAS. Xenografted tumors were transplanted into nude mice for in vivo validation. Bioinformatics analysis showed that the expression of cGAS was positively correlated with USP18 in melanoma, and USP18 was highly expressed in melanoma. The expression of cGAS and USP18 was up-regulated in cancer tissues of vemurafenib-resistant patients with BRAF V600E mutant melanoma. Knockdown of cGAS inhibited the resistance to vemurafenib in A2058R cells and the protective autophagy induced by vemurafenib in vitro. USP18 could deubiquitinate cGAS to promote its protein stability. In vivo experimentations confirmed that USP18 promoted vemurafenib-induced protective autophagy by stabilizing cGAS protein, which promoted resistance to vemurafenib in BRAF V600E mutant melanoma cells. Collectively, USP18 stabilizes cGAS protein expression through deubiquitination and induces autophagy of melanoma cells, thereby promoting the resistance to vemurafenib in BRAF V600E mutant melanoma., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Artesunate (ART) has potent anticancer activity but it suffers from poor stability and low bioavailability in vivo due to the special endoperoxide moiety in the molecules. In this work, we fabricated programmable enzyme/reactive oxygen species (ROS) responsive ART complex carriers with size and charge adaptive regulation in order to improve stability and overcome biochemical hurdles of solid tumor. The complex carries (ART/AA-PAMAM@HA) were created by electrostatic interaction between dendrimer-ART/arachidonic acid (AA) (ART/AA-PAMAM) and hyaluronic acid (HA), which can proactively penetrate deeply into tumors and selective drug release. Specifically, ART induced Fenton reaction and produced a mass of ROS and lipid peroxides (LPO), leading to the depressing of GSH level and glutathione peroxidase 4 (GPX4) activity. Meanwhile, exogenous AA further promoted the accumulation of LPO by cascade regulating ferroptosis pathway. In the anti-tumor efficacy in vivo, the tumor inhibition ratio was achieved to 46.92%. This work shows a new anti-tumor strategy triggering ferroptosis via regulating redox homeostasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Variations in size and complexity of the cerebral cortex result from differences in neuron number and composition, rooted in evolutionary changes in direct and indirect neurogenesis (dNG and iNG) that are mediated by radial glia and intermediate progenitors (IPs), respectively. How dNG and iNG differentially contribute to neuronal number, diversity, and connectivity are unknown. Establishing a genetic fate-mapping method to differentially visualize dNG and iNG in mice, we found that while both dNG and iNG contribute to all cortical structures, iNG contributes the largest relative proportions to the hippocampus and neocortex. Within the neocortex, whereas dNG generates all major glutamatergic projection neuron (PN) classes, iNG differentially amplifies and diversifies PNs within each class; the two pathways generate distinct PN types and assemble fine mosaics of lineage-based cortical subnetworks. Our results establish a ground-level lineage framework for understanding cortical development and evolution by linking foundational progenitor types and neurogenic pathways to PN types., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To understand the prevalence of insufficient physical activity among adults aged ≥18 years in China and to explore the influencing factors. Methods: The China Chronic Disease and Risk Factor Surveillance was conducted in 298 counties/districts in China in 2018, covering 31 provinces (autonomous regions, municipalities). A multi-stage stratified cluster random sampling method was used to select permanent residents aged ≥18 years. A questionnaire including Global Physical Activity Questionnaire was used to collect information about the participants' demographic characteristics and physical activity through face-to-face interview. A total of 183 769 participants completed the survey. After complex data weighting, the prevalence of insufficient physical activity, occupation, transportation, and leisure-time physical activity time was analyzed. Multivariate logistic regression models were used to analyze the influencing factors related to insufficient physical activity. Results: The prevalence of insufficient physical activity among adults aged ≥18 years was 22.3% (95% CI : 20.9%-23.7%) in China in 2018, with males [24.4% (95% CI : 23.0%-25.8%)] significantly higher than females [20.2% (95% CI : 18.6%-21.8%)]. Adults aged 70 years and above [28.4% (95% CI : 26.9%-29.9%)] were significantly higher than adults in other age groups, followed by adults aged 18-29 years [26.4% (95% CI : 24.4%- 28.3%)] and 30-39 years [23.4% (95% CI : 21.5%-25.3%)], and tended to increase with increasing education and total sedentary behavior time ( P <0.001). The weekly occupation, transportation, and leisure-time physical activity time appeared 958.6 (95% CI : 911.4-1 005.8) minutes, 234.5 (95% CI : 224.7- 244.2) minutes, and 88.6 (95% CI : 83.5-93.7) minutes, respectively. Multivariate logistic regression analysis showed that males, adults living in rural areas or northern China, ≥70 years, with junior high school education, an annual household income per capita <6 000 yuan and institutional/clerical/ technical occupation and longer total sedentary behavior time were related to a higher prevalence of insufficient physical activity. Conclusions: In China, over one-fifth of the adults had lower physical activity levels. Adults who are male, young adults, more educated, institutional/clerical/technical occupation, and with more extended total sedentary behavior are the populations that need to be focused on to promote physical activity-related health.

Diverse glutamatergic projection neurons (PNs) mediate myriad processing streams and output channels of the cerebral cortex. Yet, how different types of neural progenitors, such as radial glia (RGs) and intermediate progenitors (IPs), produce PN diversity, and hierarchical organization remains unclear. A fundamental issue is whether RGs constitute a homogeneous, multipotent lineage capable of generating all major PN types through a temporally regulated developmental program, or whether RGs comprise multiple transcriptionally heterogenous pools, each fated to generate a subset of PNs. Beyond RGs, the role of IPs in PN diversification remains underexplored. Addressing these questions requires tracking PN developmental trajectories with cell-type resolution - from transcription factor-defined RGs and IPs to their PN progeny, which are defined not only by laminar location but also by projection patterns and gene expression. Advances in cell-type resolution genetic fate mapping, axon tracing, and spatial transcriptomics may provide the technical capability for answering these fundamental questions., Competing Interests: Conflict of interest statement Nothing declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Indocyanine green (ICG) has been employed in medical diagnostics due to its superior photophysical characteristics. However, these advantages are offset by its quick body clearance and inferior photo-stability. In this work, programmable prodrug carriers for chemotherapy/PDT/PTT against nasopharyngeal carcinoma (NPC) were created in order to increase photo-stability and get around biochemical hurdles. The programmable prodrug carriers (PEG-PLA@DIT-PAMAM) that proactively penetrated deeply into NPC tumors and produced the deep phototherapy and selective drug release under laser irradiation was created by dendrimer-DOX/ICG/TPP (DIT-PAMAM) and PEGylated poly (α-lipoic acid) (PLA) copolymer. Long circulation times and minimal toxicity to mammalian cells are two benefits of PEG-coated carriers. The overexpressed GSH on the tumor cell or vascular endothelial cell of the NPC disintegrated the PEG-g-PLA chains and released the DIT-PAMAM nanoparticles after the carriers had reached the NPC tumor periphery. Small, positively charged DIT-PAMAM nanoparticles may penetrate tumors effectively and remain inside tumor for an extended period of time. In addition, the induced ROS cleaved the thioketal linkers for both DOX and nanoparticles and product hyperthermia (PTT) to kill cancer cells under laser irradiation, facilitating faster diffusion of nanoparticles and more effective tumor penetration with a programmable publication of DOX. The programmable prodrug carries showed high photo-stability high photo-stability, which enabled very effective PDT, PTT, and tumor-specific DOX release. With the goal of combining the effects of chemotherapy, PDT, and PTT against NPC, this research showed the great efficacy of programmable prodrug carriers., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare. All authors have approved the final version of the manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To assess the cardiovascular health status of adults in China by using the "Life's Essential 8" score, and provide reference for the development and improvement of cardiovascular disease prevention and control policies and measures. Methods: Chronic Disease and Nutrition Surveillance was conducted in 298 counties/districts in 2015 in 31 provinces (autonomous regions, municipalities) across China, multi-stage stratified cluster random sampling was used to select 45 households in each village or neighborhood, and 20 households were further selected to conduct dietary surveys. In this study, a total of 70 093 adults aged ≥20 years who completed the dietary survey and had complete information were included, their cardiovascular health status were assessed by using the "Life's Essential 8" score, a cardiovascular health scoring standard released by the American Heart Association in 2022. All results were adjusted using complex design-based sampling weights to achieve a better estimate of the population. Results: In 2015, the overall cardiovascular health score of Chinese adults aged ≥20 years was 73.3±12.6, the score was significantly higher in women (77.9±11.6) than in men (68.7±11.8), and higher in urban area (74.5±12.8) than in rural area (71.9±12.2), the differences were significant ( P <0.001). It was estimated that about 0.25% (95% CI : 0.16%-0.33%) of adults in China had cardiovascular health score of 100, and 33.0% (95% CI : 31.6%-34.3%), 63.2% (95% CI : 62.1%-64.3%), and 3.9% (95% CI : 3.5%-4.2%) of adults had high, moderate and low cardiovascular health scores, respectively. The proportion of those with high cardiovascular health scores was relatively low in men, those with low education level, those with low income, those living in rural areas, and those living in southwest China ( P <0.001). Of the eight factors, diet had the lowest mean score (46.0, 95% CI : 44.7-47.3), followed by blood pressure (59.4, 95% CI : 58.2-60.6) and tobacco exposure (61.4, 95% CI : 60.6-62.2). Conclusions: The cardiovascular health status of two-thirds of adult population in China needs to be improved. Diet, tobacco exposure, and blood pressure are the factors affecting the cardiovascular health of Chinese population, to which close attention needs to be paid, and men, rural residents, and those with lower socioeconomic status are key groups in cardiovascular health promotion.

Objective: To understand the health examination rate and its changing trend in adults in China from 2010 to 2018, identify the main factors affecting the health examination rate and provide data support for decision making of health intervention. Methods: Data from China Chronic Disease and Risk Factor Surveillance in 2010, 2013, 2015 and 2018 were used. After complex weighting of the data, the rates of health examination, its changing trends and reasons for receiving health examination in adults were analyzed. Average annual percent change (AAPC) was used to describe the changing trend. Anderson model was used as the analysis framework. Multivariate logistic regression model was used to identify the influencing factors for the health examination rate. Results: From 2010 to 2018, the health examination rate in adults increased from 28.2% (95% CI : 24.8%-31.6%) to 41.0% (95% CI : 38.9%-43.1%, P for trend <0.001), the AAPC was 5.47%, the annual average increase was more obvious in those with lower education level and lower income level and in those living in rural area and in western China. In 2018, people received health examination mainly due to providing without charge by community (36.7%) and working unit (28.5%). The results of multivariate analysis showed that being women, age ≥45 years, education level of junior high school or above, living in urban areas, medical insurance, annual income ≥24 000 RMB, suffering from multiple chronic diseases, non-smoking, drinking, adequate physical activity were positive factors for receiving health examination. Conclusion: The rate of health examination in adults increased in China during 2010-2018, and the main reason for receiving health examination is free of charge.

Ethnopharmacological Relevance: Children's Zibei Xuanfei syrup is an herbal preparation from a lifetime professor, famous old Chinese doctor, and postgraduate supervisor of medical doctor of Shandong University of Traditional Chinese Medicine. This herbal preparation promotes lung health, relieves cough, reduces phlegm, and benefits pharynx., Aim of the Study: To verify the clinical efficacy and safety of Zibei Xuanfei syrup for children in treatment of acute trachea bronchitis with wind-heat invading lung syndrome., Materials and Methods: This was an age-stratified, block randomized, double-blind, extremely low dose parallel control, multi-center clinical trial. A total of 453 pediatric patients diagnosed with acute tracheal bronchitis in Western medicine and cough due to exogenous factors with wind-heat invading lung syndrome in Chinese medicine were enrolled. They were divided into three subgroups based on age 1∼3, 4-7, and 8-14 years old, and randomly assigned to children's Zibei Xuanfei syrup and extremely low doses of children's Zibei Xuanfei syrup (control) in a 3:1 ratio. The primary outcome was the decreased values of cough Visual Analogue Scale (VAS) score after 7 days of administration. Secondary outcomes included a decrease in cough VAS score after 3 and 5 days of the administration, and the total score of Traditional Chinese Medicine(TCM) syndrome after 3, 5, and 7 days of treatment. The chest X-ray and blood C-reactive protein were examined during screening. The safety assessment included blood urine, and stool routine, liver and kidney function of laboratory tests, and an electrocardiogram at the screening and the last visit., Results: The subjects of two groups had high administration adherence (completion over 80%) (299/323, 92.6% in children's Zibei Xuanfei syrup group vs 103/107, 96.3% in the control group; p > 0.05). The children's Zibei Xuanfei syrup group was significantly better than the control group in the decreased values of cough VAS score after 7 days of administration(6.35 ± 3.45 vs 3.73 ± 3.98, p < 0.001). The subgroup analysis of the decreased value of cough VAS scores aged 1-3 years old were 5.80 ± 3.43 vs 3.75 ± 4.38 (P = 0.003), 4-7 years old was 6.30 ± 3.69 vs 2.73 ± 3.65 (P < 0.001), and 8-14 years old were 6.91 ± 3.12 vs 4.69 ± 3.75(P = 0.001)respectively. The secondary outcomes decrease values of cough VAS score of children's Zibei Xuanfei syrup group vs control group after 5 days of administration were 5.88 ± 2.90 vs 3.55 ± 3.41(P < 0.001), after 3 days of administration were 3.61 ± 2.53 vs 2.43 ± 2.56 (P < 0.001). The effective rate of the TCM symptom total score of children's Zibei Xuanfei syrup group vs control group was 91.38% vs 54.95%after 7 days of the administration, 86.93% vs 50.94% after 5 days of the administration, and 64.78% vs 40.19% after 3 days administration(each p < 0.001). There was no significant difference in Adverse Event between the two groups (59/331, 17.82% vs 15/111, 13.51%, P > 0.05). The children's Zibei Xuanfei syrup group had 5 Serious Adverse Events (incidence rate 1.21%), all of which were unrelated to the trial drug., Conclusion: Children's Zibei Xuanfei syrup appears to be extremely effective and safe in the treatment of acute trachea bronchitis with wind-heat invading lung syndrome. Future studies with large sample sizes will need to collect more safety data use for children., (Copyright © 2023. Published by Elsevier B.V.)

To achieve surgical anesthesia in animal experimentation, it is important to select the appropriate anesthetic dose. However, few studies have investigated the reasonable anesthetic dose in tree shrew ( Tupaia belangeri ). The aim of the study was to review the literature to determine the most commonly used anesthetic dose in tree shrew and to calculate the reasonable equivalent dose between tree shrew and rat based on the body surface area conversion. Two groups of 10 adult tree shrews each were anesthetized with 1% sodium pentobarbital through intraperitoneal injection separately at doses of 62 mg/kg (equivalent dose) and 40 mg/kg (reported dose). Anesthetic depth and times were assessed in addition to vital signs. The results showed that the dosage was quite different across studies, ranging from 15 mg/kg to 80 mg/kg, with 40 mg/kg being the most frequently reported dose. However, the group of tree shrews anesthetized with the commonly reported dose were unable to meet the requirements of surgery. In contrast, the equivalent dose (62 mg/kg, intraperitoneal injection with sodium pentobarbital) calculated by body surface area conversion could achieve an anesthetic time of 44.28 ± 3.95 min with no serious or fatal effects. During anesthetic monitoring, we found that sodium pentobarbital had an inhibitory effect on the blood pressure, pulse rate, respiratory rate and rectal temperature in tree shrews, especially on the respiratory rate. Thus, our study indicated that the use of the equivalent dose of sodium pentobarbital was effective in anesthetizing tree shrews.

Although macroalgae are regarded as the emerging fourth category of "blue carbon", few studies are available on the dynamics of dissolved organic carbon (DOC) release. Sargassum thunbergii is a typical intertidal macroalgae; and tidal action usually triggers instantaneous changes in temperature, light and salinity. Therefore, we investigated the mechanism of short-term changes in temperature, light and salinity on DOC release by S. thunbergii. As well as these factors coupled with desiccation, the combined effect of DOC release was revealed. The results showed the DOC release rate of S. thunbergii was from 0.028 to 0.037 mg C g -1 (FW) h -1 under different photosynthetically active radiation (PAR, 0-1500 μmol photons m -2  s -1 ). The DOC release rate of S. thunbergii was from 0.008 to 0.208 mg C g -1 (FW) h -1 under different salinity (5-40). The DOC release rate of S. thunbergii was from 0.031 to 0.034 mg C g -1 (FW) h -1 under different temperature (10-30 °C). Either the increase in intracellular organic matter concentration due to increased photosynthesis (change in PAR and temperature, active), cell dehydration due to dry-out process (passive) or the decrease in extracellular salt concentration (passive) would lead to an increase in the difference in osmotic pressure and promote DOC release., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Down syndrome (DS) is caused by the trisomy of human chromosome 21 (HSA21). A major challenge in DS research is to identify the HSA21 genes that cause specific symptoms. Down syndrome cell adhesion molecule (DSCAM) is encoded by a HSA21 gene. Previous studies have shown that the protein level of the Drosophila homolog of DSCAM determines the size of presynaptic terminals. However, whether the triplication of DSCAM contributes to presynaptic development in DS remains unknown. Here, we show that DSCAM levels regulate GABAergic synapses formed on neocortical pyramidal neurons (PyNs). In the Ts65Dn mouse model for DS, where DSCAM is overexpressed due to DSCAM triplication, GABAergic innervation of PyNs by basket and chandelier interneurons is increased. Genetic normalization of DSCAM expression rescues the excessive GABAergic innervations and the increased inhibition of PyNs. Conversely, loss of DSCAM impairs GABAergic synapse development and function. These findings demonstrate excessive GABAergic innervation and synaptic transmission in the neocortex of DS mouse models and identify DSCAM overexpression as the cause. They also implicate dysregulated DSCAM levels as a potential pathogenic driver in related neurological disorders., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To investigate the spatial patterns of the prevalence, awareness, treatment, and control rates of dyslipidemia at the provincial level in China., Methods: A national and provincial representative cross-sectional survey was conducted among 178,558 Chinese adults in 31 provinces in mainland China in 2018-2019, using a multi-stage, stratified, cluster-randomized sampling design. Subjects, as households, were selected, followed by a home visit to collect information. Both descriptive and linear regression procedures were applied in the analyses., Results: The overall prevalence of dyslipidemia was 35.6%, and wide geographic variations of prevalence, treatment, and control rates of dyslipidemia were identified among 178,558 eligible participants with a mean age of 55.1 ± 13.8 years. The highest-lowest difference regarding the provincial level prevalence rates were 19.7% vs. 2.1% for high low-density lipoprotein cholesterol, 16.7% vs. 2.5% for high total cholesterol, 35.9% vs. 5.4% for high triglycerides, and 31.4% vs. 10.5% for low high-density lipoprotein cholesterol. The treatment rate of dyslipidemia was correlated with the socio-demographic index ( P < 0.001), urbanization rate ( P = 0.01), and affordable basic technologies and essential medicines ( P < 0.001)., Conclusion: Prevailing dyslipidemia among the Chinese population and its wide geographic variations in prevalence, treatment, and control suggest that China needs both integrated and localized public health strategies across provinces to improve lipid management., (Copyright © 2023 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

The rapid emergence of deep learning, e.g., deep convolutional neural networks (DCNNs) as one-click image analysis with super-resolution, has already revolutionized colorimetric determination. But it is severely limited by its data-hungry nature, which is overcome by combining the generative adversarial network (GAN), i.e., few-shot learning (FSL). Using the same amount of real sample data, i.e., 414 and 447 samples as training and test sets, respectively, the accuracy could be increased from 51.26 to 85.00% because 13,500 antagonistic samples are created and used by GAN as the training set. Meanwhile, the generated image quality with GAN is better than that with the commonly used convolution self-encoder method. The simple and rapid on-site determination of Cr(VI) with 1,5-diphenylcarbazide (DPC)-based test paper is a favorite for environment monitoring but is limited by unstable DPC, poor sensitivity, and narrow linear range. The chromogenic agent of DPC is protected by the blending of polyacrylonitrile (PAN) and then loaded onto thin chromatographic silica gel (SG) as a Cr(VI) colorimetric sensor (DPC/PAN/SG); its stability could be prolonged from 18 h to more than 30 days, and its repeatable reproducibility is realized via facile electrospinning. By replacing the traditional Ed method with DCNN, the detection limit is greatly improved from 1.571 mg/L to 50.00 μg/L, and the detection range is prolonged from 1.571-8.000 to 0.0500-20.00 mg/L. The complete test time is shortened to 3 min. Even without time-consuming and easily stained enrichment processing, its detection limit of Cr(VI) in the drinking water can meet on-site detection requirements by USEPA, WHO, and China.

Objective: To explore the associations of glycated hemoglobin (HbA1c) with FPG and oral glucose tolerance test 2-hour (OGTT-2 h) in areas at different altitude in China. Methods: Subjects who participated in 2018-2019 China Chronic Disease and Risk Factor Surveillance and had no prior type 2 diabetes diagnosis were included. Subsequently, they were categorized into three groups based on altitude of living area (<2 000, 2 000- and ≥3 000 m). With adjustment for intracluster correlation, multivariable linear regression analysis was performed to evaluate the associations of HbA1c with FPG and OGTT-2 h in the context of HbA1c was normal (<5.7%) or abnormal (≥5.7%). Furthermore, the shape of relationships between HbA1c and glucose indicators was examined using restricted cubic spline. Finally, receiver operating characteristic curve was used to evaluate the diagnostic performance of HbA1c for diabetes. Results: A total of 157 277 subjects were included in the analysis. While FPG and OGTT-2 h levels gradually decreased with increase of altitude, HbA1c level was similar among the three groups. When HbA1c was <5.7%, its association with FPG and OGTT-2 h was weak and no obvious difference was observed among the three groups. When HbA1c was ≥5.7%, the FPG and OGTT-2 h increased by 15.45% (95% CI :14.71%- 16.18%) and 24.54% (95% CI :23.18%-25.91%) respectively per one standard deviation increase in HbA1c in group in area at altitude <2 000 m. However, the FPG and OGTT-2 h increased by 13.08% (95% CI :10.46%-15.76%) and 21.72% (95% CI :16.39%-27.31%), respectively, in group in area at altitude 2 000- m, and increased by 11.41% (95% CI :9.32%-13.53%) and 20.03% (95% CI :15.38%- 24.86%), respectively, in group of altitude ≥3 000 m. The restricted cubic spline indicated that the curve showing the association of HbA1c with FPG and OGTT-2 h was flat when HbA1c was <5.7%, but showed a positive linear relationship when HbA1c was ≥5.7%. The area under curve for detecting diabetes was 0.808 (95% CI :0.803-0.812) in group of altitude <2 000 m and 0.728 (95% CI :0.660-0.796, P =0.022) in group of altitude ≥3 000 m. The relevant optimal cutoff value of HbA1c was 5.7%, with a sensitivity of 65.4% and a specificity of 83.0%, and 6.0%, with a sensitivity of 48.3% and a specificity of 93.7%, respectively. Conclusions: When HbA1c was ≥5.7%, the association between HbA1c and glucose indicators became weaker as the increase of altitude. In the area at altitude ≥3 000 m, it may not be appropriate to use HbA1c in the diagnosis of diabetes.

The neocortex mediates information processing through highly organized circuitry that contains various neuron types. Distinct populations of projection neurons in different cortical regions and layers make specific connections and participate in distinct physiological functions. Herein, with the fluorescence micro-optical sectioning tomography (fMOST) and transgenetic mice that targeted intratelencephalic (IT) and pyramidal tract (PT) neurons at specific layers, we dissected the long-range connectome of pyramidal neurons in six subregions of the sensorimtor cortex. The distribution of the input neurons indicated that IT and PT neurons in the same region received information from similar regions, while the neurons in different subregions received from the preferred neuron populations. Both the input and projection areas of these six subregions showed the transverse and longitudinal correspondence in the cortico-cortical, cortico-thalamic, and cortico-striatal circuits, which indicated that the connections were topologically organized. This study provides a comprehensive resource on the anatomical connections of cortical circuits., Competing Interests: The authors declare no competing interests., (© 2023.)

Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) that can recognize pathogen-associated molecular patterns (PMPs) and play important roles in the innate immune system in vertebrates. In this study, we identified a teleost-specific tlr22 gene from yellow catfish (Pelteobagrus fulvidraco) and its immune roles in response to different pathogens were also determined. The open reading frame (ORF) of the tlr22 was 2892 bp in length, encoding a protein of 963 amino acids. Multiple protein sequences alignment, secondary and three-dimensional structure analyses revealed that TLR22 is highly conserved among different fish species. Phylogenetic analysis showed that the phylogenetic topology was divided into six families of TLR1, TLR3, TLR4, TLR5, TLR7 and TLR11, and TLR22 subfamily was clustered into TLR11 family. Meanwhile, synteny and gene structure comparisons revealed functional and evolutionary conservation of the tlr22 gene in teleosts. Furthermore, tlr22 gene was shown to be widely expressed in detected tissues except barbel and eye, with highest expression level in liver. The transcription of tlr22 was significantly increased in spleen, kidney, liver and gill tissues at different timepoints after Poly I:C infection, suggesting TLR22 plays critical roles in defensing virus invasion. Similarly, the transcription of tlr22 was also dramatically up-regulated in spleen, kidney and gill tissues with different patterns after Aeromonas hydrophila infection, indicating that TLR22 is also involved in resisting bacteria invasion. Our findings will provide a solid basis for the investigation the immune functions of tlr22 gene in teleosts, as well as provide useful information for disease control and treatment for yellow catfish., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)