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Abstract Objectives Esophagectomy after chemoradiotherapy is associated with an increased risk of surgical complications. The significance of preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio after chemoradiotherapy in predicting pulmonary complications following radical esophagectomy in esophageal squamous cell carcinoma patients receiving preoperative chemoradiotherapy remains unknown. We aimed to investigate the utility of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in predicting the pulmonary complications of esophagectomy after preoperative chemoradiotherapy. Methods We retrospectively reviewed 111 consecutive patients with stage III esophageal squamous cell carcinoma who received preoperative chemoradiotherapy followed by esophagectomy between January 2009 and December 2017. Laboratory data were collected before the operation and surgical outcomes and complications were recorded. We calculated neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and correlated them with the clinical parameters, postoperative complications, overall survival, and disease-free survival. Results Postoperative complications were observed in 75 (68%) patients, including 32 (29%) with pulmonary complications. The preoperative neutrophil-to-lymphocyte ratio of ≥ 3 (P = 0.008), clinical T4 classification (P = 0.007), and advanced stage IIIC (P = 0.012) were significantly associated with pulmonary complications. Pulmonary complication rates were 15% and 38% in patients with preoperative neutrophil-to-lymphocyte ratio of

Abstract Background Severe trauma accounts for a main factor inducing mortality for individuals aged

Abstract Background Nanotechnology holds revolutionary potential in the field of agriculture, with zinc oxide nanoparticles (ZnO NPs) demonstrating advantages in promoting crop growth. Enhanced photosynthetic efficiency is closely linked to improved vigor and superior quality in tea plants, complemented by the beneficial role of phyllosphere microorganisms in maintaining plant health. However, the effects of ZnO NPs on the photosynthesis of tea plants, the sprouting of new shoots, and the community of phyllosphere microorganisms have not been fully investigated. Results This study investigated the photosynthetic physiological parameters of tea plants under the influence of ZnO NPs, the content of key photosynthetic enzymes such as RubisCO, chlorophyll content, chlorophyll fluorescence parameters, transcriptomic and extensive targeted metabolomic profiles of leaves and new shoots, mineral element composition in these tissues, and the epiphytic and endophytic microbial communities within the phyllosphere. The results indicated that ZnO NPs could enhance the photosynthesis of tea plants, upregulate the expression of some genes related to photosynthesis, increase the accumulation of photosynthetic products, promote the development of new shoots, and alter the content of various mineral elements in the leaves and new shoots of tea plants. Furthermore, the application of ZnO NPs was observed to favorably influence the microbial community structure within the phyllosphere of tea plants. This shift in microbial community dynamics suggests a potential for ZnO NPs to contribute to plant health and productivity by modulating the phyllosphere microbiome. Conclusion This study demonstrates that ZnO NPs have a positive impact on the photosynthesis of tea plants, the sprouting of new shoots, and the community of phyllosphere microorganisms, which can improve the growth condition of tea plants. These findings provide new scientific evidence for the application of ZnO NPs in sustainable agricultural development and contribute to advancing research in nanobiotechnology aimed at enhancing crop yield and quality. Graphical Abstract

Abstract: Objective: The study investigated the effects of a short video-app-guided loving-kindness meditation (LKM) on affect, oneness belief, and proenvironmenal behavior. Methods: We recruited 93 college students from a university in China and randomized them to an LKM group (n = 47) and a wait-list control group (n = 46). The app-group engaged in an 8-week LKM intervention, while the wait-list control group underwent no intervention. We measured five major variable factors (positive affect, negative affect, oneness belief, and proenvironmenal behavior) before and after the LKM intervention. Results: In the app-group, oneness belief, positive affect, and proenvironmenal behavior were significantly higher and negative affect was significantly lower than in the wait-list control group. The wait-list control group displayed no noticeable differences in any of the four variants[variables??] between the pretest and posttest. Conclusions: Our findings demonstrate that the short video-app-guided LKM may help to improve oneness belief, positive affect, proenvironmenal behavior and reduce negative affect. The finding of the short video-app-guided LKM’s effect extends our understanding of the integrative effects of positive psychology and digital media on proenvironmenal behavior.

Jujube has a history of being used as both food and herbal medicine in China for thousands of years. Its nutritional value has long been recognized, as it contains various health-promoting bioactive components. Jujube polysaccharides are one of the major bioactive constituents. Extensive studies have shown that jujube polysaccharides exert multiple biological activities, such as antioxidant, anti-inflammatory, anti-tumor, immune regulatory, anti-fatigue, liver-protective, blood sugar-lowering, and blood lipid-lowering effects, through different or synergistic mechanisms. This article provides an overview of the physicochemical properties and structure-activity relationship of jujube polysaccharides, and summarizes the research progress on the bioactivity and mechanisms of jujube polysaccharides, both domestically and internationally in recent years. Based on these findings, the therapeutic potential of jujube polysaccharides for various diseases is discussed, aiming to provide references for further research and the development of related medicinal treatments involving jujube polysaccharides.

Societal Impact Statement Crop wild relatives represent precious genetic resources for crop improvement. Investigating their local adaptation to marginal environments is important for the utilization of wild genetic resources. Oryza officinalis and Oryza granulata are wild relatives of cultivated rice and possess genes that convey resistance to insects, disease, and tolerance to shade and drought. The northern edge for the distribution of these two lies in China where populations are facing habitat destruction. This study found that the northern marginal populations of both species have adapted to local conditions, with specific implications for the conservation and utilization of wild rice. Summary O. officinalis and O. granulata, wild relatives of cultivated rice, represent important gene reservoirs with the potential to improve rice with respect to insect resistance and stress tolerance. However, the northern marginal populations of these two species in China are facing habitat destruction. Here, we investigated the genetic diversity and divergence of northern marginal populations of O. officinalis and O. granulata. The genomic variation of two species was examined by whole‐genome sequencing on 357 individuals. Generalized dissimilarity modeling was applied to investigate the effects of geographic and environmental isolation on population differentiation. Genetic‐environment association analysis and genome‐wide FST outlier scans were used to identify environmentally driven signals of selection. The marginal populations of both species exhibited low genetic diversity and obvious genetic differentiation stemmed from the joint effects of isolation by geographic distance and the environment. Both genomes exhibited specific signals of adaptation to cold environments in the north. Investigation of the divergence and adaptation of marginal populations of O. officinalis and O. granulata will help us to determine how wild rice can adapt to local environments, thus allowing for the development of scientific conservation policies and the identification of new genetic resources for rice with improved resistance.

Achieving a high color rendering index (CRI) and luminous stability in single-structured Ce:Y3Al5O12 (Ce:YAG) phosphor ceramics (PCs) is crucial for high-power white light-emitting diodes or laser diodes (LEDs/LDs). However, cyan valleys and insufficient amounts of the red component in the Ce:YAG emission spectra significantly limit their real applications. In this work, a series of Ce,Mn:Y3(Al,Sc)2Al3O12 (Ce,Mn:YSAG) PCs were fabricated by vacuum sintering, and efficient spectral regulation was realized for full-color lighting. The cyan valley was filled by the blueshifted emission peak of Ce3+ via Sc3+ doping. The orange‒red emission at approximately 580 nm was effectively supplemented via Mn2+ doping. In particular, CRI of Ce,Mn:YSAG increased from 56.4 to 85.8, a 52% increase compared with that of Ce:YAG under high-power LED excitation, and the operating temperature was stable at approximately 50 °C for long working time. Moreover, CRI of 80.9 could still be obtained for PC-based white LDs. These results indicated that Ce,Mn:YSAG PC, which has excellent CRI and luminous stability, is an extremely promising color convertor for high-power white LEDs/LDs.

BackgroundUnhealthy lifestyles may constitute significant risk factors for dyslipidemia. However, limited studies focus on the association mentioned above among railway workers undertaking frequent shift work. ObjectiveTo understand the status of dyslipidemia and lifestyles among railway workers, and to investigate the association between the lifestyles of workers involved in different shift work schedules and dyslipidemia, aiming to provide a reference for the development of targeted intervention strategies against dyslipidemia in this occupational group. MethodsThe participants were selected from the in-service staff of a railway unit in 2021. A quota sampling approach was used to ensure the participation of at least 50% of employees from each department. Demographic and lifestyle information of the railway workers in 2021 was collected through self-administered questionnaires, while physiological and biochemical indicators were obtained through health examinations. Chi-square tests were employed to analyze the distribution of dyslipidemia among railway workers with different characteristics. Binary logistic regression was utilized to examine the associations between selected variables and dyslipidemia, and additive model was used to investigate the interaction between lifestyle and different shift work schedules on dyslipidemia. ResultsA total of 17392 railway workers were included in the study, and the total prevalence of dyslipidemia was 31.3%, with a higher prevalence reported among workers undertaking rotating night shifts (33.5%) and permanent night shifts (34.3%) than those with regular day work. The main adverse lifestyles among the railway workers were physical inactivity (59.6%), alcohol consumption (40.0%), and smoking (35.7%), and only 13.6% reported a healthy lifestyle. Furthermore, significant statistical differences in the prevalence of dyslipidemia were reported among workers with different lifestyles (P

Abstract Introduction The clinical symptoms of Lumbar Disc Herniation (LDH) can be effectively ameliorated through Lever Positioning Manipulation (LPM), which is closely linked to the brain's pain-regulating mechanisms. Magnetic Resonance Imaging (MRI) offers an objective and visual means to study how the brain orchestrates the characteristics of analgesic effects. From the perspective of multimodal MRI, we applied functional MRI (fMRI) and Magnetic Resonance Spectrum (MRS) techniques to comprehensively evaluate the characteristics of the effects of LPM on the brain region of LDH from the aspects of brain structure, brain function and brain metabolism. This multimodal MRI technique provides a biological basis for the clinical application of LPM in LDH. Methods and analysis A total of 60 LDH patients and 30 healthy controls, matched by gender, age, and years of education, will be enrolled in this study. The LDH patients will be divided into two groups (Group 1, n = 30; Group 2, n = 30) using a random number table method. Group 1 will receive LPM treatment once every two days, for a total of 12 times over 4 weeks. Group 2 will receive sham LPM treatment during the same period as Group 1. All 30 healthy controls will be divided into Group 3. Multimodal MRI will be performed on Group 1 and Group 2 at three time points (TPs): before LPM (TP1), after one LPM session (TP2), and after a full course of LPM treatment. The healthy controls (Group 3) will not undergo LPM and will be subject to only a single multimodal MRI scan. Participants in both Group 1 and Group 2 will be required to complete clinical questionnaires. These assessments will focus on pain intensity and functional disorders, using the Visual Analog Scale (VAS) and the Japanese Orthopaedic Association (JOA) scoring systems, respectively. Discussion The purpose of this study is to investigate the multimodal brain response characteristics of LDH patients after treatment with LPM, with the goal of providing a biological basis for clinical applications. Trial registration number https://clinicaltrials.gov/ct2/show/NCT05613179 , identifier: NCT05613179.

Abstract Objectives The clinical decision-making regarding choosing surgery alone (SA) or surgery followed by postoperative adjuvant chemotherapy (SPOCT) in esophageal squamous cell carcinoma (ESCC) remains controversial. We aim to propose a pre-therapy PET/CT image-based deep learning approach to improve the survival benefit and clinical management of ESCC patients. Methods This retrospective multicenter study included 837 ESCC patients from three institutions. Prognostic biomarkers integrating six networks were developed to build an ESCC prognosis (ESCCPro) model and predict the survival probability of ESCC patients treated with SA and SPOCT. Patients who did not undergo surgical resection were in a control group. Overall survival (OS) was the primary end-point event. The expected improvement in survival prognosis with the application of ESCCPro to assign treatment protocols was estimated by comparing the survival of patients in each subgroup. Seven clinicians with varying experience evaluated how ESCCPro performed in assisting clinical decision-making. Results In this retrospective multicenter study, patients receiving SA had a median OS 9.2 months longer than controls. No significant differences in survival were found between SA patients with predicted poor outcomes and the controls (p > 0.05). It was estimated that if ESCCPro was used to determine SA and SPOCT eligibility, the median OS in the ESCCPro-recommended SA group and SPOCT group would have been 15.3 months and 24.9 months longer, respectively. In addition, ESCCPro also significantly improved prognosis accuracy, certainty, and the efficiency of clinical experts. Conclusion ESCCPro assistance improved the survival benefit of ESCC patients and the clinical decision-making among the two treatment approaches. Critical relevance statement The ESCCPro model for treatment decision-making is promising to improve overall survival in ESCC patients undergoing surgical resection and patients undergoing surgery followed by postoperative adjuvant chemotherapy. Key Points ESCC is associated with a poor prognosis and unclear ideal treatments. ESCCPro predicts the survival of patients with ESCC and the expected benefit from SA. ESCCPro improves clinicians’ stratification of patients’ prognoses. Graphical Abstract

Abstract Background Esophageal cancer represents a significant public health concern; however, reliable diagnostic and prognostic markers have not been established. This study aimed to investigate the clinical value of plasma D-dimer levels in patients with esophageal cancer. Methods Overall, 120 patients with esophageal cancer who underwent radical surgical resection at our department between January 2019 and 2020 were included (esophageal cancer group). Plasma D-dimer levels were measured preoperatively and on postoperative days 1 and 14. Additionally, 60 healthy participants (control group) with measured plasma D-dimer levels were included. The preoperative D-dimer levels and positive D-dimer test rates were compared between the groups. The 3-year survival rate in patients with esophageal cancer was calculated using the Kaplan–Meier method. Results Preoperative D-dimer concentration in the esophageal cancer group was (0.65 ± 0.859 µg/mL) significantly higher than that in the control group (0.32 ± 0.369 µg/mL). The positivity rate in the esophageal cancer group (35.0%, 42/120) was significantly higher than that in the control group (15%, 9/60). D-dimer concentrations were significantly higher 1 day postoperatively than preoperatively. Conversely, D-dimer concentrations were significantly lower 14 days postoperatively than preoperatively. Patients in the esophageal cancer group with plasma D-dimer concentrations ≤ 0.5 µg/mL had significantly higher 3-year survival rates than those with higher concentrations. In the logistic multivariate analysis, tumor pathological stage and preoperative plasma D-dimer levels were independent prognostic factors of 3-year survival rates in patients with esophageal cancer. Conclusion Plasma D-dimer concentrations are clinically valuable in esophageal cancer diagnosis, postoperative recurrence monitoring, and prognosis prediction.

Abstract The synthesis of chiral α-azaheteroaryl oxiranes via enantioselective catalysis is a formidable challenge due to the required complex stereoselectivity and diverse N-heterocyclic structures. These compounds play a crucial role in developing bioactive molecules, where precise chirality significantly influences biological activity. Here we show that using chiral phosphoric acid as a catalyst, our method efficiently addresses these challenges. This technique not only achieves high enantio- and diastereoselectivity but also demonstrates superior chemo- and stereocontrol during the epoxidation of alkenyl aza-heteroarenes. Our approach leverages a synergistic blend of electrostatic and hydrogen-bonding interactions, enabling the effective activation of both substrates and hydrogen peroxide. The resulting chiral oxiranes exhibit enhanced diversity and functionality, aiding the construction of complex chiral azaaryl compounds with contiguous stereocenters. Kinetic and density functional theory studies elucidate the mechanism, highlighting chiral phosphoric acid’s pivotal role in this intricate enantioselective process.

Abstract A wideband end‐fire stepped slot antenna with gain enhancement and filtering capability is proposed. On one hand, a parasitic dipole serving as a director is introduced in the stepped slot to improve the radiation gain of the slot antenna without increasing its physical size. It is found that a gain enhancement of about 2 dB can be achieved after adopting such approach. On the other hand, an absorptive branch possessing a nearly complementary frequency response with regard to the one of the slot antenna is in‐parallel loaded at the microstrip feedline. It allows the partial dissipation of the out‐of‐band/non‐radiated RF‐signal power of the antenna to attain both an RF‐quasi‐absorptive behaviour and filtering capability. It is found that after loading the dissipative branch, the out‐of‐band radiation efficiency of the slot antenna is reduced to less than 20%. The measured results of a fabricated proof‐of‐concept antenna prototype show a reasonable agreement with the simulated ones and verify the RF performance merits of the proposed stepped slot antenna, such as wide RF operating band covering the 3.39−4.73‐GHz range, end‐fire radiation with a front‐to‐back ratio (FBR) above 10 dB, flat radiation gain, and co‐integrated filtering functionality with RF‐quasi‐absorptive capability.

Abstract Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells (ECs) that play an important role in liver development and regeneration. Additionally, it is involved in various pathological processes, including steatosis, inflammation, fibrosis and hepatocellular carcinoma. However, the rapid dedifferentiation of LSECs after culture greatly limits their use in vitro modeling for biomedical applications. In this study, we developed a highly efficient protocol to induce LSEC-like cells from human induced pluripotent stem cells (hiPSCs) in only 8 days. Using single-cell transcriptomic analysis, we identified several novel LSEC-specific markers, such as EPAS1, LIFR, and NID1, as well as several previously revealed markers, such as CLEC4M, CLEC1B, CRHBP and FCN3. These LSEC markers are specifically expressed in our LSEC-like cells. Furthermore, hiPSC-derived cells expressed LSEC-specific proteins and exhibited LSEC-related functions, such as the uptake of acetylated low density lipoprotein (ac-LDL) and immune complex endocytosis. Overall, this study confirmed that our novel protocol allowed hiPSCs to rapidly acquire an LSEC-like phenotype and function in vitro. The ability to generate LSECs efficiently and rapidly may help to more precisely mimic liver development and disease progression in a liver-specific multicellular microenvironment, offering new insights into the development of novel therapeutic strategies.

Abstract Transition metal compounds with kagome structure have been found to exhibit a variety of exotic structural, electronic, and magnetic orders. These orders are competing with energies very close to each other, resulting in complex phase transitions. Some of the phases are easily observable, such as the charge density wave (CDW) and the superconducting phase, while others are more challenging to identify and characterize. Here we present magneto-transport evidence of a new phase below ~ 35 K in the kagome topological metal CsV3Sb5 (CVS) thin flakes between the CDW and the superconducting transition temperatures. This phase is characterized by six-fold rotational symmetry in the in-plane magnetoresistance (MR) and is connected to the orbital current order in CVS. Furthermore, the phase is characterized by a large in-plane negative magnetoresistance, which suggests the existence of a three-dimensional, magnetic field-tunable orbital current ordered phase. Our results highlight the potential of magneto-transport to reveal the interactions between exotic quantum states of matter and to uncover the symmetry of such hidden phases.

Introduction: With the increasing emphasis on the use of nonanimal ingredients in clinical care, studies have proposed the use of TrypLE™ as an alternative to trypsin. However, previous research has reported insufficient cell yield and viability when using TrypLE to isolate skin cells compared to the dispase/trypsin-EDTA method. This study aimed to propose an improved method for increasing the yield and viability of cells isolated by TrypLE and to evaluate isolated keratinocytes and melanocytes. Methods: Foreskin tissues were isolated to keratinocytes and melanocytes using the trypsin-EDTA protocol and our modified TrypLE protocol. The yield and viability of freshly isolated cells were compared, the epidermal residue after cell suspension filtration was analyzed histologically, and the expression of cytokeratin 14 (CK14) and Melan-A was detected by flow cytometry. After cultivation, keratinocytes and melanocytes were further examined for marker expression and proliferation. A coculture model of melanocytes and HaCaT cells was used to evaluate melanin transfer. Results: The yield, viability of total cells and expression of the keratinocyte marker CK14 were similar for freshly isolated cells from both protocols. No differences were observed in the histologic analysis of epidermal residues. Moreover, no differences in keratinocyte marker expression or melanocyte melanin transfer function were observed after culture. However, melanocytes generated using the TrypLE protocol exhibited increased Melan-A expression and proliferation in culture. Conclusion: Our TrypLE protocol not only solved the problems of insufficient cell yield and viability in previous studies but also preserved normal cell morphology and function, which enables the clinical treatment of depigmentation diseases.

Prostate stromal cells play a crucial role in the promotion of tumor growth and immune evasion in the tumor microenvironment (TME) through intricate molecular alterations in their interaction with prostate cancer (PCa) cells. While the impact of these cells on establishing an immunosuppressive response and influencing PCa aggressiveness remains incompletely understood. Our study shows that the activation of the leukemia inhibitory factor (LIF)/LIF receptor (LIFR) pathway in both prostate tumor and stromal cells, following androgen deprivation therapy (ADT), leads to the development of an immunosuppressive TME. Activation of LIF/LIFR signaling in PCa cells induces neuroendocrine differentiation (NED) and upregulates immune checkpoint expression. Inhibition of LIF/LIFR attenuates these effects, underscoring the crucial role of LIF/LIFR in linking NED to immunosuppression. Prostate stromal cells expressing LIFR contribute to NED and immunosuppressive marker abundance in PCa cells, while LIFR knockdown in prostate stromal cells reverses these effects. ADT‐driven LIF/LIFR signaling induces brain‐derived neurotrophic factor (BDNF) expression, which, in turn, promotes NED, aggressiveness, and immune evasion in PCa cells. Clinical analyses demonstrate elevated BDNF levels in metastatic castration‐resistant PCa (CRPC) and a positive correlation with programmed death‐ligand 1 (PDL1) and immunosuppressive signatures. This study shows that the crosstalk between PCa cells and prostate stromal cells enhances LIF/LIFR signaling, contributing to an immunosuppressive TME and NED in PCa cells through the upregulation of BDNF.

Abstract Background Metabolic plasticity mediates breast cancer survival, growth, and immune evasion during metastasis. However, how tumor cell metabolism is influenced by and feeds back to regulate breast cancer progression are not fully understood. We identify hypoxia-mediated suppression of pyruvate carboxylase (PC), and subsequent induction of lactate production, as a metabolic regulator of immunosuppression. Methods We used qPCR, immunoblot, and reporter assays to characterize repression of PC in hypoxic primary tumors. Steady state metabolomics were used to identify changes in metabolite pools upon PC depletion. In vivo tumor growth and metastasis assays were used to evaluate the impact of PC manipulation and pharmacologic inhibition of lactate transporters. Immunohistochemistry, flow cytometry, and global gene expression analyzes of tumor tissue were employed to characterize the impact of PC depletion on tumor immunity. Results PC is essential for metastatic colonization of the lungs. In contrast, depletion of PC in tumor cells promotes primary tumor growth. This effect was only observed in immune competent animals, supporting the hypothesis that repression of PC can suppress anti-tumor immunity. Exploring key differences between the pulmonary and mammary environments, we demonstrate that hypoxia potently downregulated PC. In the absence of PC, tumor cells produce more lactate and undergo less oxidative phosphorylation. Inhibition of lactate metabolism was sufficient to restore T cell populations to PC-depleted mammary tumors. Conclusions We present a dimorphic role for PC in primary mammary tumors vs. pulmonary metastases. These findings highlight a key contextual role for PC-directed lactate production as a metabolic nexus connecting hypoxia and antitumor immunity. Graphical abstract

Abstract The surface quality of steel strip is a critical indicator of the quality of hot‐rolled strip, so accurate inspection of its surface is essential. However, the complex texture of steel strip surface defects makes the detection challenging. Here, a multi‐scale feature fusion and attention based YOLOv5 (MFFA‐YOLOv5) model is proposed. Specifically, the bottom layer features are up‐sampled and fused not only with the middle layer features, but also with the top layer features, so that the model better captures the surface texture information of the steel strip. Secondly, an improved attention mechanism module is introduced to deal with the global and local information of the steel strip surface by introducing down‐sampling and up‐sampling paths based on Convolutional Block Attention Module (CBAM). Meanwhile, a self‐attention mechanism path is added to improve the capability of feature representation. Experimental results on the NEU‐DET dataset show that the MFFA‐YOLOv5 model significantly outperforms other state‐of‐the‐art methods.

Fluorotelomer sulfonates (FTSs) are widely used as novel substitutes for perfluorooctane sulfonate, inevitably leading to FTSs accumulation in various environmental media and subsequent exposure to humans. This accumulation eventually poses environmental hazards and health risks. However, their toxicity mechanisms remain unclear. Herein, the mechanisms of two FTSs (6:2 and 8:2 FTS) induced toxicity in human hepatocellular carcinoma cells were investigated via non-targeted metabolomics and lipidomics based on liquid chromatography–high resolution mass spectrometry. Our results revealed that amino acid, purine, acylcarnitine and lipid levels were significantly perturbed by 6:2 and 8:2 FTS exposure. The effects of 8:2 FTS exposure were largely characterized by up-regulation of pyruvate metabolism pathway and down-regulation of purine metabolism pathway, whereas the opposite trends were induced by 6:2 FTS exposure. The opposite trends were confirmed by the mRNA expression levels of four key genes (glyoxalase 1, adenylosuccinate lyase, inosine monophosphate dehydrogenase 1 (IMPDH1) and IMPDH2) determined by real-time PCR. Common lipid perturbations included significantly increased ceramide/sphingomyelin ratios, and obvious accumulation of hexosylceramides and lysoglycerophospholipids. 6:2 FTS exposure induced sharp accumulation of glycerides, including monoglycerides, diglycerides and triglycerides. 8:2 FTS exposure induced decreased levels of acylcarnitines and fatty acids. Both of 6:2 and 8:2 FTS exposure induced increased levels of intracellular reactive oxygen species, an imbalance in energy metabolism homeostasis, and mitochondrial dysfunction. The results of integrated omics analysis are expected to serve as valuable information for the health risk assessment of 6:2 FTS and 8:2 FTS.

IntroductionThis study examined the efficacy and safety of neoadjuvant chemotherapy combined with immunotherapy in patients with muscle-invasive bladder cancer (MIBC).MethodsThis retrospective cohort study included patients diagnosed with MIBC at the First Affiliated Hospital of Soochow University between January 1, 2020, and December 31, 2023, assigned to either chemotherapy (gemcitabine with cisplatin) or combination (chemotherapy plus toripalimab or tislelizumab) groups based on the neoadjuvant treatment regimen. Key metrics, including pathological downstaging rate (PDR), pathological complete response rate (PCRR), and incidence and severity of adverse events (AEs), were compared between groups.ResultsThis study included 53 patients (mean age: 67.21 years). In the combination group, 14 patients (51.85%) achieved pathological complete remission (ypT0), and seven (25.93%) achieved partial remission (ypT1), resulting in a PDR and PCRR of 77.78 and 51.85%, respectively. In the chemotherapy group, six patients (23.08%) achieved complete remission, and five (19.23%) achieved partial remission, resulting in a PDR and PCRR of 42.31 and 23.08%, respectively. Differences between groups were statistically significant (p < 0.05). There were no significant differences in pathological downstaging or complete remission rates among subgroups in the combination group (p > 0.05). No serious allergic reactions or fatal AEs were detected in either group, with no grade 4 AEs. Grade 3 AE rates were 22.22 and 20.83% in the combination and chemotherapy groups, respectively, although non-significant (p > 0.05).ConclusionNeoadjuvant chemotherapy combined with immunotherapy had enhanced efficacy and manageable safety in patients with MIBC, suggesting its potential for integration into clinical practice.

Background: The incidence of a disease can help health professionals to identify risk factors and health-care policymakers to develop corresponding policies. The realization of both purposes depends on comprehensive studies, especially studies done on a large scale. However, comprehensive studies on the incidence of anaphylaxis among inpatients in China are still notably scarce. Hence we aim to explore the incidence and clinical characteristics of anaphylaxis among inpatients over a span of 21 years in Wuhan, China. Methods: We retrieved data on anaphylaxis cases from the Data Platform Application Portal (DPAP) across 3 medical centers of Tongji Hospital, Wuhan, China from January 1, 2003, to December 31, 2023. Results: The data encompassed a total of 362 anaphylaxis patients from 2,139,272 inpatients. Among them 204 (56.4%) were male, and the median age was 45 years old. Over the past 2 decades, the incidence rate of anaphylaxis at Tongji Hospital was 16.92 per 100,000 individuals. After adjusting for gender and age, the annual standardized incidence rate was 234.53 per 100,000 individuals. The incidence rate of anaphylaxis among the inpatients revealed a relatively stable but slowly rising trend over the 21-year observation period. As for the triggers of anaphylaxis, drugs were responsible for 73.6% of triggers, with antibiotics representing the highest proportion of these cases (38.4%). Drug triggers also showed age-specific features: chemotherapy (17.9%) had the highest proportions among children aged 0–3 years; blood products were more prevalent in school-age children. 13.5% of the cases had an unknown cause. In anaphylaxis cases, despite that only 36.0% received epinephrine treatment, the application of epinephrine still showed an ascending trend. Moreover, the mortality rate for anaphylaxis was relatively low (1.6%), displaying a consistent downward trend. Conclusion: Our study provides insights into the incidence of anaphylaxis among inpatients in Wuhan over a 21-year period. Drugs are the most common triggers for anaphylaxis, and the use of epinephrine in anaphylaxis management is far from optimal.

BackgroundSchistosomiasis japonica is a serious threat to human health. It causes damage to the intestine and liver. Probiotic therapy has been shown to be effective in alleviating intestinal diseases and improving host health. Previous studies have found that Bacillus amyloliquefaciens could alleviate the pathological symptoms of schistosomiasis japonica, but the regulatory mechanism of alleviating schistosomiasis japonica is still unknown.Principal findingsThis study analyzed the dynamic changes of intestinal microbiome in mice infected with Schistosoma japonicum after the intervention of B. amyloliquefaciens and its connection to host metabolism by multi-omics sequencing technology. B. amyloliquefaciens was found to significantly regulate the homeostasis of intestinal microbiota by promoting the growth of beneficial bacteria and inhibiting potential pathogenic bacteria and protect the number of core microbes. Meanwhile, the genes related to the metabolism of glycerophospholipids and amino acid from intestinal microbiome changed significantly, and were shown to be significantly positively correlated with the associated metabolites of microbial origin. Moreover, host metabolism (lipid metabolism and steroid hormone biosynthesis) was also found to be significantly regulated.ConclusionsThe recovery of intestinal microbial homeostasis and the regulation of host metabolism revealed the potential probiotic properties of B. amyloliquefaciens, which also provided new ideas for the prevention and adjuvant treatment of schistosomiasis japonica.

The developing world continues to face substantial obstacles to achieving affordable and dependable electricity access. This issue is especially pertinent for Nigeria, where diesel generators are widely relied upon in urban and rural regions because of an underdeveloped and unreliable national grid. The lack of grid reliability is worsened in Northeastern Nigeria, an area plagued by conflict, extreme poverty, and grid infrastructure deterioration. This study investigates the feasibility of implementing community-scale microgrids in rural areas without grid connection access. It focuses on assessing the technical, economic, and environmental aspects of utilizing these microgrids to deliver inexpensive and dependable electricity to underserved populations to increase energy access. A case study was conducted in Kabuiri, a village with an estimated population of 2,300 residents and an estimated load demand of 610 kWh per day. A hybrid microgrid system was designed and optimized to meet the community’s load demand using HOMER software, sized to produce 610 kWh/day of electricity with a renewable penetration of 99%. The optimal solar PV/battery/generator system had a levelized cost of electricity (LCOE) of $ 0.093 per kWh, a net present cost (NPC) of $266,709, and an annual operating cost of $9,110. The system contributed 1,624 kg CO2 eq/year of global warming potential and 56.81 kg O3 eq/year of smog formation during operation. Sensitivity analysis showed that the system could effectively react to or adapt to substantial increases in diesel prices, requiring only marginal increases in photovoltaic capacity and reduced generator usage to maintain the most cost-efficient operation. Additionally, the system model can be adapted based on the population of the remote community without substantially impacting the LCOE, however, the NPC increases with increase in population size. This research will aid in increasing energy access in remote locations by providing insights to stakeholders and energy access project developers.

BackgroundOxidative stress plays a significant role in aging and cancer, yet there is currently a lack of research utilizing machine learning models to examine the relationship between oxidative stress and prognosis in elderly non-small cell lung cancer (NSCLC) patients.MethodsThis study included elderly NSCLC patients who underwent radical lung cancer resection from January 2012 to April 2018, exploring the relationship between Oxidative Stress Score (OSS) and prognosis. Machine learning techniques, including Decision Trees (DT), Random Forest (RF), and Support Vector Machine (SVM), were employed to develop predictive models for 5-year overall survival (OS).ResultsThe datasets consisted of 1647 patients in the training set, 705 in the internal validation set, and 516 in the external validation set. An OSS was formulated from six systemic oxidative stress biomarkers, such as albumin, total bilirubin, and blood urea nitrogen, among others. Boruta variable importance analysis identified low OSS as a key indicator of poor prognosis. The OSS was subsequently integrated into the DT, RF, and SVM models for training. These models, optimized through hyperparameter tuning on the training set, were then evaluated on the internal and external validation sets. The RF model demonstrated the highest predictive performance, with an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.794 in the internal validation set, compared to AUCs of 0.711 and 0.760 for the DT and SVM models, respectively. Similarly, in the external validation set, the RF model achieved an AUC of 0.784, outperforming the DT and SVM models, which had AUCs of 0.699 and 0.730, respectively. Calibration plots confirmed the RF model’s superior calibration, followed by the SVM model, with the DT model performing the poorest.ConclusionThe OSS-based clinical prediction model, constructed using machine learning methodologies, effectively predicts the prognosis of elderly NSCLC patients post-radical surgery.

Remnant cholesterol (RC) is highly regarded in the cardiovascular field; however, its relationship with new-onset diabetes remains unclear. This study aimed to investigate the relationship between RC and the risk of developing diabetes, as well as its interaction with low-density lipoprotein cholesterol (LDL-c). This was a secondary analysis of a retrospective cohort study based on a Chinese population. A multivariate Cox proportional hazards regression was initially employed to assess the relationship between RC and newly diagnosed diabetes. This was followed by a subgroup analysis to explore intergroup heterogeneity. A clinical prediction model was then developed. Finally, the study further analyzed the interactions between LDL-c and RC. After adjusting for confounding factors, RC was significantly associated with an increased risk of diabetes (HR = 1.46, 95% CI 1.36-1.57). Furthermore, this relationship was nonlinear, with an inflection point of 0.48 identified through the piecewise model. Subgroup analysis indicated that the association was more pronounced in individuals under 60 years and those with a BMI

Research suggests that physical cleansing leads individuals to perceive themselves as morally purer, thereby influencing their moral activities, but findings are inconsistent. Some researchers have found that individuals act more morally after physical cleansing, whereas others have observed the reverse effect. Building on embodied cognition theory, which holds that cognition is developed from physical experience and that this experience in turn guides their responses, we hypothesized that physical cleansing would have a general impact on individuals' moral activities by highlighting themselves. In contrast to previous research, we did not expect that physical cleansing would directly make people more (im)moral. Two experiments were conducted to test our hypotheses. In experiment 1, participants who had bathed showed reduced susceptibility to external moral priming (morality-related descriptions of themselves) than did control participants. Experiment 2 showed that physical cleansing (but not the control condition) amplified the interplay among participants' moral activities, depending on the order of immoral behavior and intention measurement. Taken together, these results suggest that physical cleansing strengthens the connection between individuals' morality and bodily experiences, weakening the effect of external priming (experiment 1) and enhancing the influence of moral activities performed by themselves (experiment 2). Although further research is required to provide direct evidence for these findings, our study contributes to the integration of inconsistencies in previous findings by suggesting a new perspective for the understanding of the embodied effect of physical cleansing.

BackgroundStudies have shown the positive impact of perceived social support on cognitive function among older adults in rural areas. However, existing studies often overlook the impact of different support sources. This study aimed to explore the relationship between the diverse sources of perceived social support and cognitive function.MethodsParticipants were drawn from the Guizhou Rural Older Adults’ Health Study (HSRO) in China. We included 791 participants who participated in a baseline survey in 2019 and a 3-year follow-up survey. Perceived social support was investigated from the six main sources (friend, relative, children, spouse, sibling, and neighbor). Hierarchical linear regression models were used to observe the effects of diverse sources of perceived social support and their combinations on cognitive function.ResultsCognitive function was positively associated with perceived support from children, friends, and neighbors. A positive association was found between cognitive function and increases in each additional source [β = 0.75 (95%CI: 0.51, 0.98), p

ABSTRACT The intact immune system of mice exhibits resistance to colonization by exogenous microorganisms, but the gut microbiota profiles of the humanized mice and the patterns of human fecal microbiota colonization remain unexplored. Humanized NCG (huNCG) mice were constructed by injected CD34 +stem cells. 16S rRNA sequencing and fecal microbiota transplantation (FMT) technologies were used to detect the differences in microbiota and selective colonization ability for exogenous community colonization among three mice cohorts (C57BL/6J, NCG, and huNCG). Flow cytometry analysis showed that all huNCG mice had over 25% hCD45 +in peripheral blood. 16S rRNA gene sequence analysis showed that compared with NCG mice, the gut microbiota of huNCG mice were significantly altered. After FMT, the principal coordinates analysis (PCoA) showed that the gut microbial composition of huNCG mice (huNCG-D9) was similar to that of donors. The relative abundance of Firmicutes and Bacteroidetes were significantly increased in huNCG mice compared to NCG mice. Further comparison of ASV sequences revealed that Bacteroides plebeius, Bacteroides finegoldii, Escherichia fergusonii, Escherichia albertii, Klebsiella pneumoniae, and Klebsiella variicola exhibited higher abundance and stability in huNCG mice after FMT. Furthermore, PICRUSt2 analysis showed that huNCG mice had significantly enhanced metabolism and immunity. This study demonstrated that humanized mice are more conducive to colonization within the human gut microbiota, which provides a good method for studying the association between human diseases and microbiota.IMPORTANCEThe gut microbiota and biomarkers of humanized mice are systematically revealed for the first time. The finding that human fecal microbiota colonize humanized mice more stably provides new insights into the study of interactions between immune responses and gut microbiota.

IntroductionThe rapid initiation of antiretroviral therapy (ART) and its impact on treatment outcomes have been a subject of global public health interest. However, the precise mechanisms underlying the effects of rapid ART initiation remain unclear.MethodsThis retrospective cohort study examined data from 1846 HIV-infected individuals in Jiulongpo District, Chongqing, China, spanning from 2016 to 2022. Logistic regression models and serial mediation analysis were used to explore the influence of rapid ART initiation on treatment outcomes and the role of medication adherence as a mediating factor.ResultsThe findings revealed a significant association between rapid ART initiation and reduced risk of viral failure (adjusted odds ratio [OR] = 0.320, 95% confidence interval [CI] = [0.161, 0.637]), as well as an increased likelihood of improved adherence (adjusted OR = 2.053, 95% CI = [1.226, 3.438]). Medication adherence was identified as a partial mediator in the relationship between rapid ART initiation and viral failure, explaining 10.5% of the total effect.DiscussionIn conclusion,rapid initiation of antiretroviral therapy was found to enhance treatment outcomes, emphasizing the importance of early adherence education. The study recommends early initiation of ART coupled with adherence education and psychological counseling for HIV-infected individuals.

Due to differences in raw materials and production processes, different spirits exhibit various flavor even if undergo distillation operation. In this study, sensory analysis could clearly distinguish 5 types spirits, and had been validated through quantitative targeted flavoromics analysis. Consequently, 44 potential differential markers between 5 types spirits were screened. Among, 34 definite differential markers were further confirmed to be highly correlated with target sensory attributes and could effectively distinguish types of spirits. Ultimately, 14 key differential markers (including 2-methylbutane, linalool, acetaldehyde, d-limonene, β-myrcene, phenylethyl alcohol, phenethyl acetate, heptyl formate, ethyl octanoate, ethyl decanoate, ethyl pentanoate, ethyl hexanoate, hexanoic acid, and ethyl hexadecanoate) could reveal the chemical sources of spirit sensory and serve as targets for identifying different types of spirits. Overall, the results of flavoromic characterization of 5 types spirits provided a significant step forwards in understanding of differentiation of spirits by sensory coupled with quantitative, and statistical analysis

Aberrant energy metabolism in the brain is a common pathological feature in the preclinical Alzheimer's Disease (AD). Recent studies have reported the early elevations of glycolysis-involved enzymes in AD brain and cerebrospinal fluid according to a large-scale proteomic analysis. It’s well-known that astrocytes exhibit strong glycolytic metabolic ability and play a key role in the regulation of brain homeostasis. However, its relationship with glycolytic changes and cognitive deficits in early AD patients is unclear. Here, we investigated the mechanisms by which astrocyte glycolysis is involved in early AD and its potential as a therapeutic target. Our results suggest that Aβ-activated microglia can induce glycolytic-enhanced astrocytes in vitro, and that these processes are dependent on the activation of the AKT-mTOR-HIF-1α pathway. In early AD models, the increase in L-lactate produced by enhanced glycolysis of astrocytes leads to spatial cognitive impairment by disrupting synaptic plasticity and accelerating Aβ aggregation. Furthermore, we find rapamycin, the mTOR inhibitor, can rescue the impaired spatial memory and Aβ burden by inhibiting the glycolysis-derived L-lactate in the early AD models. In conclusion, we highlight that astrocytic glycolysis plays a critical role in the early onset of AD and that the modulation of glycolysis-derived L-lactate by rapamycin provides a new strategy for the treatment of AD.

Study Region: Continental Argentina, South America. Study Focus: This study integrates multiple data sources to analyze the response of vegetation to meteorological and groundwater drought events in Argentina. It utilizes GRACE satellite data to monitor water storage variations, the GLDAS hydrological model to track soil moisture levels, and NDVI to assess vegetation health, categorized by different vegetation types. Meteorological data facilitated the computation of drought severity using the Standardized Precipitation-Evapotranspiration Index (SPEI). Anomalies in groundwater storage, derived from these data, informed the calculation of the Grace Groundwater Drought Index (GGDI). A comprehensive statistical analysis was conducted to examine the impact of meteorological (SPEI) and groundwater (GGDI) droughts on various vegetation types. New Hydrological Insights for the Region: The study reveals that from 2002 to 2022, GRACE-TWSA and GLDAS-TWSA displayed consistent trends in Argentina. Meteorological droughts, characterized by higher frequency and intensity, predominantly affect croplands and grasslands. Compared to lagged effects, the cumulative impact of droughts was found to be more significant. Shrublands demonstrated the greatest resistance to drought, whereas vegetation in humid regions showed lower drought tolerance. Notably, the duration associated with the lag effects of meteorological droughts decreased from 2.16 months in 2002–1.52 months in 2020, suggesting an increasing sensitivity of vegetation to these droughts. This underscores the urgency of developing targeted drought resilience and water resource management strategies.

Mycoplasma gallisepticum (MG) is a pathogen that induces chronic respiratory illnesses in chickens, leading to tracheal and lung injury, and eliciting immune reactions that support sustained colonization. Baicalin, a compound found in scutellaria baicalensis, exhibits anti-inflammatory, antioxidant, and antibacterial properties. This study aimed to investigate the potential of baicalin in alleviating lung and cell damage caused by MG by restoring imbalances in M1/M2 and Th1/Th2 differentiation and to explore its underlying mechanism. In this research, a model for M1/M2 polarization induced by MG was initially developed. Specifically, infection with MG at a multiplicity of infection (MOI) of 400 for 6 h represented the M1 model, while infection for 10 h represented the M2 model. The polarization markers were subsequently validated using qRT-PCR, ELISA, and Western blot analysis. Baicalin disrupts the activation of M1 cells induced by MG and has the potential to restore the balance between M1 and M2 cells, thereby mitigating the inflammatory damage resulting from MG. Subsequent studies on MG-infected chickens detected imbalances in M1/M2 and Th1/Th2 differentiation in alveolar lavage fluid, as well as imbalances in macrophages and Th cells in the lung. The M1/Th1 model was exposed to MG for 5 d, while the M2/Th2 model was infected with MG for 7 d. The utilization of both light and electron transmission microscopes revealed that the administration of baicalin resulted in a reduction in the number of M1 cells, a decrease in cytoplasmic vacuoles, restoration of mitochondrial swelling and chromatin agglutination, as well as alleviation of alveolar rupture and inflammatory cell infiltration. Furthermore, baicalin restored MG-induced M1/M2 and Th1/Th2 imbalances and inhibited the phosphorylation of p38 and p65 proteins, thereby hindering the activation of the TLR4-p38 MAPK/NF-κB pathway. This study provides insights into the potential long-term effects of baicalin in MG infection and offers a theoretical basis for practical applications.

This paper systematically investigates the changes in material properties during electrohydrodynamic (EHD) drying, the discharge characteristics of the EHD system as well as the active ingredients, textural properties (hardness, adhesiveness, etc.) and moisture distribution of yam under EHD, air drying and hot air drying were investigated. The results showed that the active particles and the ionized wind generated during the discharge process of the electrohydrodynamic drying device had a significant effect on the drying. Compared to thermal drying, 21 kV drying resulted in the most complete cellular structure, the best internal bound water content as well as textural properties of yam. It played a positive role in the retention of internal nutrients in yam, and the total phenol and allantoin contents were increased by 25.74% and 81.99%, respectively. These results elucidate the advantages of electrohydrodynamic drying in yam drying and provide a reference for the application of EHD in drying.

ABSTRACT Purpose: To examine whether isoflurane preconditioning (IsoP) has a protective effect against renal ischemia/reperfusion injury (I/RI) in diabetic conditions and to further clarify the underlying mechanisms. Methods: Control and streptozotocin-induced diabetic rats were randomly assigned to five groups, as follows: normal sham, normal I/R, diabetic sham, diabetic I/R, and diabetic I/R + isoflurane. Renal I/RI was induced by clamping renal pedicle for 45 min followed by reperfusion for 24 h. IsoP was achieved by exposing the rats to 2% isoflurane for 30 min before vascular occlusion. Kidneys and blood were collected after reperfusion for further analysis. Renal histology, blood urea nitrogen, serum creatinine, oxidative stress, inflammatory cytokines, and renal cell apoptosis were assessed. Furthermore, the expression of brahma related gene 1 (Brg1), nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and nuclear factor-κB (NF-κB) were determined. Results: Compared with control, diabetic rats undergoing I/R presented more severe renal injury, oxidative stress, inflammatory reaction, and apoptosis with the impairment of Brg1/Nrf2/HO-1 signaling. All these alterations were significantly attenuated by pretreatment with isoflurane. Conclusions: These findings suggest that isoflurane could alleviate renal I/RI in diabetes, possibly through improving Brg1/Nrf2/HO-1 signaling.

Abstract Quasi‐2D perovskites light‐emitting diodes (PeLEDs) have achieved significant progress due to their superior optical and electronic properties. However, the blue PeLEDs still exist inefficient energy transfer and electroluminescence performance caused by mixed multidimensional phase distribution. In this work, transition metal salt (zinc bromide, ZnBr2) is introduced to modulate phase distributions by suppressing the nucleation of high n phase perovskites, which effectively shortens the energy transfer path for blue emission. Moreover, ZnBr2 also facilitates energy level matching and reduces non‐radiative recombination, thus improving electroluminescence (EL) efficiency. Benefiting from these combined improvements, an efficient blue PeLEDs is obtained with a maximum external quantum efficiency (EQE) of 16.2% peaking located at 486 nm. This work provides a promising approach to tune phase distribution of quasi‐2D perovskites and achieving highly efficient blue PeLEDs.

Accurate identification of Mycobacterium tuberculosis (M. tuberculosis) is a critical step in the diagnosis of tuberculosis. Existing object detection methods struggle with the challenges posed by the varied morphology and size of M. tuberculosis in sputum smear images, which makes precise targeting difficult. To solve these problems, an improved YOLOv8s model is proposed. Specifically, an additional detection head is added to focus on small target information. Second, a multi-scale feature fusion module is introduced to adapt the model to different sizes of M. tuberculosis. In addition, a convolutional layer is added to the Coordinate Attention (CA) module to extract more advanced semantic features. Finally, a self-attention mechanism is added after the CA module to enhance the model's ability to accurately understand and localize the varied morphology of M. tuberculosis. Our model performed well with an average precision of 85.7 % when tested on a publicly available dataset. This clearly demonstrates the effectiveness of our proposed model in M. tuberculosis detection.

Objectives: To compare the diagnostic value of histogram analysis derived from diffusion weighted imaging (DWI) and diffusion kurtosis imaging (DKI) in differentiating the mismatch repair (MMR) status of rectal adenocarcinoma. Methods: DWI and DKI were performed in 124 patients with rectal adenocarcinoma, which were divided into deficient mismatch repair (dMMR) group and proficient mismatch repair (pMMR) group. The patients' general clinical information, pathology and image characteristics were compared. The histogram analysis of apparent diffusion coefficient (ADC), diffusion kurtosis (K) and diffusion coefficient (D)derived from DWI and DKI at b values of 1000 and 2000 s/mm2 were calculated. The diagnostic efficacy of quantitative parameters for MMR in rectal adenocarcinoma was compared. Results: The mean, 50th, 75th and 90th in ADC quantitative parameters of dMMR group were lower when the b value was 2000 s/mm2 (all P

Intratumoral microbiota (IM) has emerged as a significant component of the previously thought sterile tumor microenvironment (TME), exerting diverse functions in tumorigenesis and immune modulation. This review outlines the historical background, classification, and diversity of IM, elucidating its pivotal roles in oncogenicity, cancer development, and progression, alongside its influence on anti-tumor immunity. The signaling pathways through which IM impacts tumorigenesis and immunity, including reactive oxygen species (ROS), β-catenin, stimulator of interferon genes (STING), and other pathways [NF-κB, Toll-like receptor (TLR), complement, RhoA/ROCK, PKR-like ER kinase (PERK)], are discussed comprehensively. Furthermore, we briefly introduce the clinical implications of IM, emphasizing its potential as a target for novel cancer therapies, diagnostic biomarkers, and prognostic indicators. Notably, microbe-based therapeutic strategies such as fecal microbiome transplantation (FMT), probiotics regulation, bacteriotherapy, bacteriophage therapy, and oncolytic virotherapy are highlighted. These strategies hold promise for enhancing the efficacy of current cancer treatments and warrant further exploration in clinical settings.

Abstract Background Cancer cachexia affects more than half of all cancer patients, reducing survival rates. Evidence‐based approaches are urgently needed to optimize treatment. Methods A systematic review and network meta‐analysis were conducted to assess the effectiveness and safety of different pharmacotherapies for cancer cachexia. Three databases (PubMed, Cochrane Library, and Web of Science) were searched for the period from January 1, 2000, to March 20, 2024. The netmeta package in R software was used to calculate the pooled effect, employing a random effects model. Results Seven placebo‐controlled randomized trials involving 1421 patients were analyzed. Pairwise analysis showed that body weight increases were 4.6 kg (95% confidence interval [CI] 0.83–8.37 kg) for olanzapine, 3.82 kg (95% CI 0.73–6.91 kg) for espindolol (20 mg), 2.36 kg (95% CI 1.84–2.89 kg) for anamorelin (100 mg), and 1.31 kg (95% CI 0.42–2.19 kg) for anamorelin (50 mg). In terms of safety profiles, olanzapine demonstrated the lowest odds ratio when compared to placebo, at 0.26 (95% CI 0.07–0.94), followed by anamorelin (50 mg) at 0.86 (95% CI 0.30–2.48), and anamorelin (100 mg) at 0.89 (95% CI 0.42–1.88). However, network meta‐analysis could not confirm the superiority of olanzapine over anamorelin in terms of efficacy and safety. Conclusion Both olanzapine and anamorelin are useful in improving body weight in patients with cancer cachexia. Personalization may be helpful for different patients.

Abstract Tumor recurrence is a life‐threatening complication after liver transplantation (LT) for hepatocellular carcinoma (HCC). Precise recurrence risk stratification before transplantation is essential for the management of recipients. Here, we aimed to establish an inflammation‐related prediction model for posttransplant HCC recurrence based on pretransplant peripheral cytokine profiling. Two hundred and ninety‐three patients who underwent LT in two independent medical centers were enrolled, and their pretransplant plasma samples were sent for cytokine profiling. We identified four independent risk factors, including alpha‐fetoprotein, systemic immune‐inflammation index, interleukin 6, and osteocalcin in the training cohort (n = 190) by COX regression analysis. A prediction model named inflammatory fingerprint (IFP) was established based on the above factors. The IFP effectively predicted posttransplant recurrence (area under the receiver operating characteristic curve [AUROC]: 0.792, C‐index: 0.736). The high IFP group recipients had significantly worse 3‐year recurrence‐free survival rates (37.9 vs. 86.9%, p

BackgroundTeduglutide, the first glucagon-like peptide 2 analogue, has been demonstrated to facilitate the absorption of gut nutrient and lessen the need for parenteral assistance in patients with Short Bowel Syndrome (SBS). However, its adverse drug events (AEs) are primarily documented in clinical trials, with a deficit in real-world data. This study evaluates the AEs profile of teduglutide based on Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) data.MethodA disproportionality analysis of FAERS data from Quarter 1 (Q1) 2013 to Quarter 3 (Q3) 2023 was conducted to examine the association between teduglutide and adverse events, employing Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM) methods.ResultsOut of 13,809,302 reports in the FAERS database, 10,114 reports identified teduglutide as the “primary suspect” in AEs identification. During the dosing observation period, the median occurrence of adverse events was 393 days (interquartile range [IQR] 97–996 days). Teduglutide-associated AEs occurred in 27 System Organ Classes (SOC), of which renal and urinary disorders is not mentioned in the specification. Based on the four algorithms, a total of 260 major disproportionality preferred terms (PTs) were filtered out, including previously unreported AEs including weight decreased (n = 805), vascular device infection (n = 683), dehydration (n = 596) and nephrolithiasis (n = 146).ConclusionOur findings corroborate the AEs listed in the teduglutide prescribing information and additionally unveil new adverse reaction signals such as nephrolithiasis. These discoveries could aid in clinical monitoring and risk identification for teduglutide.