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Zuo Wang,1,2,&ast; Siqi Guo,3,&ast; Chong He,2,4,&ast; Lingling Chen,5 Jinxia Wang,2 Wenbo Xiu,2 Gao Zhang,2 Yang Chen,2 An Li,2 Xiong Zhu,6 Xiao Xiao,2 Ling Yu,3 Fang Lu2,4,7 1Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Department of Ophthalmology, Daping Hospital, Army Medical Center, Army Medical University, Chongqing, People’s Republic of China; 4Medico-Engineering Cooperation on Applied Medicine Research Center, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 5Department of Immunology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, People’s Republic of China; 6Department of Prenatal Diagnosis, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 7Health Management Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Yu; Fang Lu, Email oculistlingyu@hotmail.com; lufangfang@126.comObjective: Evidence suggests that dysbiosis of the gut microbiota plays a pivotal role in the development of glaucoma. This dysbiosis is commonly associated with chronic intestinal inflammation and increased intestinal permeability. However, the understanding of intestinal inflammation and permeability in glaucoma remains insufficient. This study aims to investigate the potential relationship between fecal inflammation and permeability markers and glaucoma.Methods: We recruited 114 glaucoma patients and 75 healthy controls. Levels of fecal lactoferrin (Lf) and alpha-1 antitrypsin (AAT) were quantified using enzyme linked immunosorbent assay (ELISA) to compare both biomarkers between groups and across different severity grades of glaucoma. Logistic regression analysis was used to assess the association between these fecal biomarkers and glaucoma. The severity of glaucoma was assessed based on the mean deviation (MD) in the visual field.Results: In this study, we observed elevated levels of fecal Lf and AAT in glaucoma patients. The proportion of glaucoma patients with abnormal fecal Lf levels (≥ 7.25 μg/g) was significantly higher than that of the controls (p = 0.012). A positive correlation was noted between fecal Lf and AAT (rho = 0.20, p = 0.006). After adjusting for age and sex, multivariable logistic regression analysis indicated that both fecal Lf (OR = 1.11, 95% CI: 1.01– 1.21, p = 0.026) and AAT (OR = 1.01, 95% CI: 1.01– 1.02, p < 0.001) positively correlated with glaucoma. These biomarkers might reflect glaucoma severity, with significant differences in fecal Lf levels observed between moderate and severe stages, but not in the early stage. Furthermore, increasing levels of fecal AAT correlated with greater severity of glaucomatous injury and a larger vertical cup-to-disc ratio (VCDR) (p < 0.05).Conclusion: This study suggests an increase in intestinal inflammation and permeability in glaucoma, further indicating the importance of the ‘gut-retina axis’ in the pathogenesis of the disease and potentially offering new therapeutic avenues.Keywords: fecal lactoferrin, fecal alpha-1 antitrypsin, glaucoma, intestinal inflammation, intestinal permeability, intestinal barrier

**Background:** Japanese patients with prostate cancer are typically treated with primary androgen deprivation therapy (ADT), most commonly administered as a combination of a luteinizing hormone-releasing hormone (LHRH) agonist and an antiandrogen (AA). Since LHRH agonists and AA therapy can be maintained for several years, the long-term effects of these treatments on patients must be carefully considered, including the risk of concomitant central nervous system (CNS) conditions which could affect treatment choices. **Objective:** To describe CNS-related concomitant conditions during ADT and/or AA treatment and the subsequent healthcare resource utilization in Japanese nonmetastatic castration-resistant prostate cancer (nmCRPC) patients. **Methods:** Patients diagnosed with nmCRPC and CNS-related conditions while on ADT and/or AA therapy between April 2009 and August 2017 were retrospectively followed up for a maximum of 2 years using a claims database. **Results:** A total of 455 patients (average age, 78.5 years), were included. The 3 most common concomitant CNS-related conditions were pain (~60% of events), insomnia (~30%), and headache (2%-3%). The frequency of CNS-related conditions in these patients increased approximately threefold after starting AA therapy (before, 969 events; after, 2802). On average, a patient had 10 episodes of concomitant CNS-related conditions in a year. Medical costs did not significantly increase due to CNS-related conditions. **Discussion:** The most frequently reported CNS-related conditions were pain, insomnia, and headaches. Furthermore, more concomitant CNS-related conditions 1 year after CRPC diagnosis and 1 year after starting AA treatment were recorded. **Conclusion:** Patients with nmCRPC experience an increase in the frequency of concomitant CNS-related conditions, including pain, insomnia, and headaches, after CRPC diagnosis or starting AA treatment. Future research should explore the causes of this increased frequency.

Heng Dong,1,&ast; Kaili Yang,2,&ast; Yu Zhang,1 Qiang Li,1 Weijun Xiu,2 Meng Ding,1 Jingyang Shan,3 Yongbin Mou1 1Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China; 2Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Centre for Advanced Materials (SICAM), Nanjing University of Posts and Telecommunications, Nanjing, People’s Republic of China; 3Department of Neurology, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, 518000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongbin Mou, Nanjing Stomatological Hospital, Medical School of Nanjing University, #30 Zhongyang Road, Nanjing, 210008, People’s Republic of China, Email yongbinmou@163.com; yongbinmou@nju.edu.cn Jingyang Shan, Department of Neurology, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, 518000, People’s Republic of China, Email jyshandr@163.comBackground: Bacterial biofilm-related wound infections threaten human health due to the lack of efficient treatments. Therefore, developing a novel strategy for wound infection care is urgently needed.Methods: Cube-shaped Cu2WS4 nanocrystals (CWSNs) were successfully prepared via a microwave-assisted method. CWSNs, as photocatalysts, were first studied by using fluorescence spectroscopy for their ability to generate reactive oxygen species (ROS). The antibacterial and biofilm inhibition abilities of CWSNs were determined in vitro by using Staphylococcus aureus (S. aureus) as the model bacterium. Moreover, a CWSN gel was prepared and applied to treat S. aureus-infected wounds in mice. The toxicity of the CWSNs was evaluated through in vitro cell and in vivo animal experiments.Results: Studies on the properties of the CWSNs demonstrated that these nanomaterials can catalyze the generation of hydroxyl radicals (•OH) without the addition of H2O2 after visible-light irradiation, indicating their photocatalytic ability. Moreover, the in vitro experimental results showed that the CWSNs not only adhered to the surfaces of S. aureus to kill the bacteria, but also inhibited S. aureus biofilm formation. The in vivo study showed that the CWSN gel produced excellent antibacterial effects against S. aureus infected wounds in mice and effectively promoted wound healing. Furthermore, toxicity tests showed that the CWSNs have negligible toxicity in vitro and in vivo.Conclusion: This work provides a potential photocatalytic antibacterial nanoagent for efficient bacterial killing, inhibition of biofilms growth and wound infection treatment.Graphical Abstract: Keywords: Cu2WS4 nanocrystals, Staphylococcus aureus, visible light, hydroxyl radical, antibacterial, biofilms

Xiang Xu,1,&ast; Qiwei Dong,1,&ast; Qingling Zhong,2 Wenbo Xiu,1,2 Qinyuan Chen,1,2 Jinxia Wang,1 Zhou Zhou1,2 1Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Gastroenterology and Hepatology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhou ZhouClinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of ChinaTel +86-028-87394201Fax +86-028-87394201Email doublezhou2006@126.comBackground: Irritable bowel syndrome (IBS) is characterized with abdominal pain, bloating, and changes in bowel habits, and dealing with IBS is still a clinical challenge. The pathogenesis of IBS has been reported to be linked to low-grade mucosal inflammation, and macrophages contribute to the pathological process of this disease. Kurarinone (KAR), a flavanoid derived from Sophora flavescens, has been found medically effective in many inflammatory conditions and cancers. KAR was previously reported to inhibit LPS-induced expression of inflammatory cytokines in macrophages, whether and how KAR regulates the functions of macrophage in IBS remains to be elusive.Methods: We established a TNBS-induced IBS mouse model, in which KAR was administrated, and mucosal cytokine expression was measured by qRT-PCR. Additionally, mouse macrophages were generated in vitro and their responses to LPS were evaluated by flow cytometry and qRT-PCR. AhR+/+ or AhR−/- macrophages were transferred into DTx-treated CD11b-DTR transgenic mice to investigate the role of AhR in IBS. We collected colonic biopsies and peripheral blood samples from 64 patients with IBS, and analyzed AhR expression by qRT-PCR.Results: We found KAR effectively alleviated visceral hypersensitivity and maintained intestinal barrier functions in mice with IBS. KAR inhibited LPS-induced macrophage activation and expression of pro-inflammatory genes, while increased anti-inflammatory gene expression including IL-10 in an AhR-dependent manner. Using macrophage-depleted mice, we found that chimera mice with AhR−/- macrophages were more susceptible to TNBS-induced IBS and the therapeutic effect of KAR on IBS was significantly impaired in mice with AhR−/- macrophages. Additionally, we found AhR expression in macrophages of IBS patients was associated with the disease severity.Conclusion: Our findings provide new evidences that KAR regulates IBS development via macrophage-intrinsic AhR. KAR might show promise as an immunomodulatory therapeutic agent in treating IBS.Keywords: aryl hydrocarbon receptor, irritable bowel syndrome, macrophage, kurarinone, flavonoid

Ling Yu,1,&ast; Yang Chen,2,&ast; Xiang Xu,2 Qiwei Dong,2,3 Wenbo Xiu,2 Qinyuan Chen,2 Jinxia Wang,2 Chong He,2,3 Jian Ye,1 Fang Lu2,3 1Department of Ophthalmology, Daping Hospital, Army Medical Center, Army Medical University, Chongqing, People’s Republic of China; 2Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Medico-Engineering Cooperation on Applied Medicine Research Center, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang LuClinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, 32 The First Ring Road West 2, Chengdu, Sichuan, 610072, People’s Republic of ChinaTel/Fax +86-028-87394201Email lufangfang@126.comJian YeDepartment of Ophthalmology, Daping Hospital, Army Medical Center, Army Medical University, No. 10, Changjiang Branch, Daping, Yuzhong District, Chongqing, 400042, People’s Republic of ChinaTel/Fax +86-023-68811229Email yejian1979@163.comBackground: Glaucoma is a group of retinal neurodegenerative diseases causing irreversible visual impairment. The pathogenesis of this disease is complicated. Studies have shown that the immune system is involved in the neurodegenerative process of glaucoma. There are continuous evidences that autoantibodies play a crucial role in the pathogenesis of glaucoma. However, focuses on B cells, the antibody-producing cells in glaucoma are surprisingly limited.Methods: Fresh peripheral blood samples were collected from 44 glaucoma patients (38 with primary angle-closure glaucoma (PACG) and 6 with (primary open-angle glaucoma POAG)) and 36 age-matched healthy donors (HD). Density gradient centrifugation was performed to obtain peripheral blood mononuclear cells (PBMC). Flow cytometry was performed to determine B cell phenotypes. The severity of glaucoma was determined based on the mean deviation (MD) of visual field.Results: In this study, we demonstrated that total B cells was significantly increased in glaucoma patients compared to HD. Next, we checked changes of different B cell subsets in glaucoma. Glaucoma patients were found to have a significant increase in the frequencies of antibody-secreting cells (ASC)/plasmablasts, naïve, and CD19+ CD27− IgD− double negative (DN) subpopulations, but a decrease in the CD27+ IgD+ unswitched memory compartment. Notably, we found that the increment of CD27− IgD− DN B cells was significantly magnified according to the clinical severity.Conclusion: We demonstrate, for the first time, that peripheral B cell subsets are altered and unveil the correlation of a newly identified pro-inflammatory CD27− IgD− DN subset with clinical features of glaucoma, suggesting that these B cell subsets could serve as potential biomarkers to monitor the disease progression of glaucoma patients.Keywords: glaucoma, B cells, CD27− IgD− double negative B cells, retinal neurodegeneration

Iodate reduction by dissimilatory iodate-reducing microorganisms (DIRMs) plays a crucial role in the biogeochemical cycling of iodine on Earth. However, the occurrence and distribution of DIRMs in iodine-rich groundwater remain unclear. In this study, we isolated the dissimilatory iodate-reducing bacterium Azonexus hydrophilus strain NCP973 from a geogenic high-iodine groundwater of China for the first time. The analysis of genome, transcriptome, and heterologous expression revealed that strain NCP973 uses the dissimilatory iodate-reducing enzyme IdrABP1P2 to reduce dissolved or in situ sediment-bound iodate to iodide. The location of IdrABP1P2 in the conjugative plasmid of strain NCP973 implies that IdrABP1P2 could be spread by horizontal gene transfer and allow the recipient microorganisms to participate in the enrichment of iodide in aquifers. Based on the global iodine-rich groundwater metagenomes and genomes, the identification of idrA showed that phylogenetically diverse DIRMs are widely distributed not only in geogenic high-iodine groundwater of China but also in radionuclide-contaminated groundwater of USA as well as in subsurface cavern waters in Germany and Italy. Moreover, the abundance of idrA was found to be higher in groundwater with a relatively high iodine content. Collectively, these results suggest that terrestrial iodine-affected groundwater systems are another important habitat for DIRMs in addition to marine environments, and their activity in aquifers triggers the mobilization and enrichment of iodine in groundwater worldwide.

Antibacterial therapy targeting the regulation of macrophage polarization may be a useful approach for normalizing the immune environment and accelerating wound healing. Inspired by black phosphorus-based nanoplatforms, more stable yet less-explored violet phosphorus nanosheets (VPNSs) are expected to provide a superior solution for effectively combating bacterial infections. In this study, an average thickness of 5-7 nm VPNSs are fabricated through the liquid-phase exfoliation method to serve as an immunoregulatory dressing for the treatment of infected wounds. VPNSs attenuated excessive reactive oxygen species (ROS) and reduced the accumulation of proinflammatory M1 macrophages, showing notable antioxidant and anti-inflammatory properties. Comprehensive RNA sequencing further elucidated the potential immunoregulatory mechanisms of VPNSs, including modulation of the inflammatory response and enzyme regulator activity. Additionally, the inherent photothermal properties of the VPNSs contributed significantly to their antibacterial efficacy. When combined with near-infrared laser irradiation, VPNSs showed remarkable effectiveness in reducing infection-related complications and expediting wound healing in infected skin wound models. The rapid promotion of wound healing through ROS clearance, the regulation of macrophage polarization, and hyperthermia generation underscores the potential of the violet-phosphorus-based nanoplatforms as clinically viable agents for treating infected wounds. This study suggests that VPNSs are promising candidates for clinical anti-infective and anti-inflammatory applications., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical., Methods: We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients. Next, we evaluated the combinational efficacy in murine SCLC. The tumor immune microenvironment (TIME) was analyzed for mechanistic study. Subsequently, we conducted a multicenter, prospective phase II trial that administered concurrent thoracic LDRT plus chemoimmunotherapy to treatment-naive ES-SCLC patients (MATCH trial, NCT04622228). The primary endpoint was confirmed objective response rate (ORR), and the key secondary endpoints included progression-free survival (PFS) and safety., Findings: Fifteen refractory SCLC patients treated with LDRT plus ICI were retrospectively reviewed. The ORR was 73.3% (95% confidence interval [CI], 44.9-92.2). We identified a specific dose of LDRT (15 Gy/5 fractions) that exhibited growth retardation and improved survival in murine SCLC when combined with ICIs. This combination recruited a special T cell population, TCF1 + PD-1 + CD8 + stem-like T cells, from tumor-draining lymph nodes into the TIME. The MATCH trial showed a confirmed ORR of 87.5% (95% CI, 75.9-94.8). The median PFS was 6.9 months (95% CI, 5.4-9.3)., Conclusions: These findings verified that LDRT plus chemoimmunotherapy was safe, feasible, and effective for ES-SCLC, warranting further investigation., Funding: This research was funded by West China Hospital (no. ZYJC21003), the National Natural Science Foundation of China (no. 82073336), and the MATCH trial was fully funded by Roche (China) Holding Ltd. (RCHL) and Shanghai Roche Pharmaceuticals Ltd. (SRPL)., Competing Interests: Declaration of interests Y. Lu has an invited speaker/project lead/principal investigator role with Roche, AstraZeneca, and BeiGene and an invited speaker role with Pfizer, Merck Sharp & Dohme, and Bristol-Myers Squibb. L.Z., Y. Zhang, M.H., Y.G., Y. Liu, J.Z., and B.Z. have an invited investigator role with Roche. J.S., C.X., H.W.,(9) L. Wu, Z. Yuan, N.B., M.F., and Yaping Xu have an invited principal investigator role with Roche., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Type 2 diabetes mellitus (T2D) causes complications due to metabolic disorders besides increasing blood glucose. Sweet corn cob selenium polysaccharide (SeSCP) is a complex of Se with Sweet corn cob polysaccharide that has good hypoglycemic efficacy, but its effect on T2D metabolism has not been determined. In this study, the hypoglycemic effect of SeSCP was investigated by in vitro and in vivo experiments, and the levels of metabolites in feces were analyzed in a high-fat diet and STZ-induced T2D mouse model by Liquid chromatography-mass spectrometry (LC-MS). The results indicated that SeSCP regulates α-amylase and α-glucosidase through competitive reversible inhibition, and the reaction is spontaneous, driven by van der Waals forces and hydrogen bonding. In vivo, SeSCP modulates glucose transport decreasing glucose entry into the bloodstream. The metabolites mainly affected by SeSCP-MC were adenine, LysoPA (0:0/18:2(9Z, 12Z)), cysteine-S-sulfate, and demeclocycline (hydrochloride) metabolites. SeSCP interfered with β-alanine metabolism, starch and sucrose metabolism, ether lipid metabolism, glycerophospholipid metabolism, glyoxylate and dicarboxylate metabolism, pantothenate and CoA biosynthesis, etc. Additionally, SeSCP exhibited more effective metabolic interventions than metformin and SCP. Therefore, SeSCP can reduce complications while improving T2D blood glucose., 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.)

Purpose: Taxol is the first-line chemo-drug for advanced non-small cell lung cancer (NSCLC), but it frequently causes acquired resistance, which leads to the failure of treatment. Therefore, it is critical to screen and characterize the mechanism of the taxol-resistance reversal agent that could re-sensitize the resistant cancer cells to chemo-drug., Method: The cell viability, sphere-forming and xenografts assay were used to evaluate the ability of ASIV to reverse taxol-resistance. Immunohistochemistry, cytokine application, small-interfering RNA, small molecule inhibitors, and RNA-seq approaches were applied to characterize the molecular mechanism of inhibition of epiregulin (EREG) and downstream signaling by ASIV to reverse taxol-resistance., Results: ASIV reversed taxol resistance through suppression of the stemness-associated genes of spheres in NSCLC. The mechanism exploration revealed that ASIV promoted the K48-linked polyubiquitination of EREG along with degradation. Moreover, EREG could be triggered by chemo-drug treatment. Consequently, EREG bound to the ErbB receptor and activated the ERK signal to regulate the expression of the stemness-associated genes. Inhibition of EREG/ErbB/ERK could reverse the taxol-resistance by inhibiting the stemness-associated genes. Finally, it was observed that TGFβ and Hedgehog signaling were downstream of EREG/ErbB/ERK, which could be targeted using inhibitors to reverse the taxol resistance of NSCLC., Conclusions: These findings revealed that inhibition of EREG by ASIV reversed taxol-resistance through suppression of the stemness of NSCLC via EREG/ErbB/ERK-TGFβ, Hedgehog axis., (© 2024. Springer Nature Switzerland AG.)

Backgroud: Intussusception is a common acute abdominal disease in children, often leading to acute ileus in infants and young children., Objective: This study aimed to develop and validate a nomogram for predicting recurrent intussusception in children within 48 h after pneumatic reduction of primary intussusception., Methods: Clinical data of children with acute intussusception admitted to multiple hospitals from March 2019 to March 2021 were retrospectively analyzed. The children were divided into a successful reductioncontrol group (control group) and a recurrent intussusception group (RI group) according to the results of pneumatic reduction., Results: A total of 2406 cases were included in this study, including 2198 control group and 208 RI group. In the total sample, 1684 cases were trained and 722 cases were verified. A logistic regression analysis was conducted to establish a predictive model based on age, abdominal pain time, white blood cells count, and hypersensitive C-reactive protein levels as independent predictors of intussusception recurrence. The nomogram successfully predicted recurrent intussusception after pneumatic reduction., Conclusion: In this study, a nomogram was developed based on clinical risk factors to predict recurrent intussusception following pneumatic reduction in children. Age, abdominal pain time, white blood cell counts, and hypersensitive C-reactive protein levels were identified as predictors and incorporated into the nomogram. Internal validation demonstrated that this nomogram can offer a clear and convenient tool for identifying risk factors for recurrence of intussusception in children undergoing pneumatic reduction., (© 2024. The Author(s).)

In the field of numerical control machining, tool alignment technology is a key link to ensure machining accuracy and quality. Tool alignment refers to determining the correct position of the tool relative to the workpiece, and its accuracy directly affects the precision of part machining. With the development of precision machining technology, the research and application of cutting technology are increasingly valued. Tool alignment methods are mainly divided into two categories: contact and non-contact. The contact type tool alignment method relies on direct contact between the tool and the workpiece or tool alignment instrument to measure the position. Among them, the trial cutting method is a traditional contact type tool alignment method that determines the tool position through actual cutting, which is intuitive but inefficient. The contact type tool presetter uses specialized equipment to improve the accuracy and efficiency of tool presetting through contact measurement. The non-contact tool alignment method does not rely on physical contact, while the image method uses image recognition technology to determine the tool position, making it suitable for high-precision applications. The laser diffraction method and the laser direct method use laser technology for non-contact measurement. The laser diffraction method determines the position of the tool by analyzing the diffraction mode of the laser beam, while the laser direct method directly measures the distance between the laser and the tool. This article mainly introduces the classification of tool alignment, commonly used knife alignment methods and common tool alignment devices, as well as the development status of international tool alignment instrument products.

High‑arsenic (As) groundwater in geothermal aquifers poses a serious threat to public health. Assembly processes governing groundwater microbial community related to As biotransformation are still unexplored in geothermal groundwater across different aquifers. To fill this gap, groundwater microorganisms, community assembly processes, and microbially metabolic coupling of carbon (C), nitrogen (N), phosphorus (P), sulfur (S), and arsenic (As) were investigated in unconfined and confined groundwater in the thermal reservoirs of the Guide Basin. The difference in groundwater hydrogeochemicals led to the heterogeneity of the microbial community and microbially mediated C, N, P, S, and As cycling between unconfined and confined groundwater. Higher temperature and As concentrations, low nutrient supply, and reduced conditions in confined groundwater supported stronger interspecific coexistence and environmental selection, thus promoting the proliferation of As-resistant microorganisms (ARMs) and simplifying the community assemblage. Abundant available nutrient supply and oxidizing conditions supported an increased species diversity and metabolic functionality in unconfined groundwater. S oxidizers, C fixation, and C degradation bacteria potentially contributed to the decreased As concentrations in unconfined groundwater. However, ARMs, ammonification, and anaerobic ammonia-oxidizing bacteria potentially caused As mobilization in confined groundwater. Overall, our results give a comprehensive insight into the interaction between As and microorganisms in geothermal groundwater., 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.)

Low temperature has been a major challenge for lithium-ion batteries (LIBs) to maintain satisfied electrochemical performance, and the main reason is the deactivation of electrolyte with the decreasing temperature. To address this point, in present work, we develop a low-temperature resistant electrolyte which includes ethyl acetate (EA) and fluoroethylene carbonate (FEC) as solvent and lithium difluoro(oxalato)borate (LiDFOB) as the primary lithium salt. Due to the preferential decomposition of LiDFOB and FEC, a solid electrolyte interface rich in LiF is formed on the lithium metal anodes (LMAs) and lithium cobalt oxide (LCO) cathodes, contributing to higher stability and rapid desolvation of Li + ions. The batteries with the optimized electrolyte can undergo cycling tests at -40 °C, with a capacity retention of 83.9 % after 200 cycles. Furthermore, the optimized electrolyte exhibits excellent compatibility with both LCO cathodes and graphite (Gr) anodes, enabling a Gr/LCO battery to maintain a capacity retention of 90.3 % after multiple cycles at -25 °C. This work proposes a cost-effective electrolyte that can activate potential LIBs in practical scenarios, especially in low-temperature environments., (© 2024 Wiley-VCH GmbH.)

Elevated serum cholesterol metabolism is associated with a reduced risk of lung cancer. Disrupted cholesterol metabolism is evident in both lung cancer patients and tumor cells. Inhibiting tumor cell cholesterol uptake or biosynthesis pathways, through the modulation of receptors and enzymes such as liver X receptor and sterol-regulatory element binding protein 2, effectively restrains lung tumor growth. Similarly, promoting cholesterol excretion yields comparable effects. Cholesterol metabolites, including oxysterols and isoprenoids, play a crucial role in regulating cholesterol metabolism within tumor cells, consequently impacting cancer progression. In lung cancer patients, both the cholesterol levels in the tumor microenvironment and within tumor cells significantly influence cell growth, proliferation, and metastasis. The effects of cholesterol metabolism are further mediated by the reprogramming of immune cells such as T cells, B cells, macrophages, myeloid-derived suppressor cells, among others. Ongoing research is investigating drugs targeting cholesterol metabolism for clinical treatments. Statins, targeting the cholesterol biosynthesis pathway, are widely employed in lung cancer treatment, either as standalone agents or in combination with other drugs. Additionally, drugs focusing on cholesterol transportation have shown promise as effective therapies for lung cancer. In this review, we summarized current research regarding the rule of cholesterol metabolism and therapeutic advances in lung cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 The Authors.)

Although aboveground biodiversity has been extensively studied, the impact of nutrient enrichment on soil microbial populations remains unclear. Soil microorganisms serve as important indicators in shaping soil nutrient cycling processes and are typically sensitive to nutrient additions. For this, we employed a factorial combination design to examine the impact of nutrient additions on the composition and function of soil bacteria in a temperate steppe. Nitrogen addition promoted the growth of copiotrophic bacteria (Proteobacteria, Firmicutes, and Bacteroidota) but inhibited the growth of oligotrophic bacteria (Acidobacteria, Chloroflexi, and Verrucomicrobiota). Phosphorus addition alleviated phosphorus deficiency, resulting in a decrease in the abundance of phoD-harboring bacteria (Actinobacteria and Proteobacteria). Significant enhancement of soil bacterial alpha diversity was observed only in treatments with added phosphorus. Changes in NO 3 - -N, NH 4 + -N, available phosphorus, and dissolved organic carbon resulting from nutrient addition may have a greater impact on microbial community structure than changes in soil pH caused by nitrogen addition. Moreover, nutrient addition may indirectly impact microbial ecological function by altering nutrient availability in the soil. In conclusion, our study suggests that soil nutrient availability, particularly available phosphorus, affects soil bacterial communities and potentially regulates the biogeochemical cycles of soil ecosystems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Jiang, Zhang, Zhu, Wang, Xiu, Zhao, Liu, Zhang and Yang.)

Background: To construct a nomogram for predicting necrotizing enterocolitis (NEC) in preterm infants., Methods: A total of 4,724 preterm infants who were admitted into 8 hospitals between April 2019 and September 2020 were initially enrolled this retrospective multicenter cohort study. Finally, 1,092 eligible cases were divided into training set and test set based on a 7:3 ratio. A univariate logistic regression analysis was performed to compare the variables between the two groups. Stepwise backward regression, LASSO regression, and Boruta feature selection were utilized in the multivariate analysis to identify independent risk factors. Then a nomogram model was constructed based on the identified risk factors., Results: Risk factors for NEC included gestational diabetes mellitus, gestational age, small for gestational age, patent ductus arteriosus, septicemia, red blood cell transfusion, intravenous immunoglobulin, severe feeding intolerance, and absence of breastfeeding. The nomogram model developed based on these factors showed well discriminative ability. Calibration and decision curve analysis curves confirmed the good consistency and clinical utility of the model., Conclusions: We developed a nomogram model with strong discriminative ability, consistency, and clinical utility for predicting NEC. This model could be valuable for the early prediction of preterm infants at risk of developing NEC., Competing Interests: Conflict of 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 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Due to the presence of spatial barriers, persistent bacteria, and excessive inflammation in bacteria biofilm-infected wounds, current nanoplatforms cannot effectively address these issues simultaneously during the therapeutic process. Herein, a novel biomimetic photothermal nanoplatform integrating silver and polydopamine nanoparticles (Ag/PDAs) that can damage biofilms, kill bacterial persisters, and reduce inflammation for wound treatment is presented. These findings reveal that Ag/PDAs exhibit a broad-spectrum antimicrobial activity through direct damage to the bacterial membrane structure. Additionally, Ag/PDAs demonstrate a potent photothermal conversion efficiency. When combined with near-infrared (NIR) irradiation, Ag/PDAs effectively disrupt the spatial structure of biofilms and synergistically eradicate the resident bacteria. Furthermore, Ag/PDAs show remarkable anti-inflammatory properties in counteracting bacterium-induced macrophage polarization. The in vivo results confirm that the topical application of Ag/PDAs significantly suppress Staphylococcus aureus biofilm-infected wounds in murine models, concurrently facilitating wound healing. This research provides a promising avenue for the eradication of bacterial biofilms and the treatment of biofilm-infected wounds., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

Objective: This study was designed to investigate the effects of hypertensive disorders of pregnancy (HDP) on the complications in very low birth weight (VLBW) neonates., Methods: We retrospectively included VLBW neonates (<37 weeks) who were delivered by HDP pregnant women with a body weight of < 1,500 g (HDP group) hospitalized in our hospital between January 2016 and July 2021. Gestational age matched VLBW neonates delivered by pregnant women with a normal blood pressure, with a proportion of 1:1 to the HDP group in number, served as normal control., Results: Then we compared the peripartum data and major complications between HDP group and control. The body weight, prelabor rupture of membrane (PROM), maternal age, cesarean section rate, fetal distress, small for gestational age (SGA), mechanical ventilation, RDS, necrotizing enterocolitis (NEC) (≥2 stage), Apgar score at 1 min, and mortality in HDP group showed statistical differences compared with those of the control (all p  < 0.05). To compare the major complications among HDP subgroups, we classified the VLBW neonates of the HDP group into three subgroups including gestational hypertension group ( n  = 72), pre-eclampsia (PE) group ( n  = 222), and eclampsia group ( n  = 14), which showed significant differences in the fetal distress, Apgar score at 1 min, SGA, ventilation, RDS and NEC (≥2 stage) among these subgroups (all p  < 0.05). Multivariate regression analysis showed that eclampsia and PE were the independent risk factors for SGA and NEC, respectively., Conclusion: HDP was associated with increased incidence of neonatal asphyxia, fatal distress, SGA, mechanical ventilation, RDS, NEC and mortality. Besides, eclampsia and PE were independent risk factors for SGA and NEC.

Aims: To explore rare and difficult cases of undifferentiated embryonal sarcoma of the liver (UESL) in children in a single centre, summarize the diagnosis and treatment experience and analyse the role of a computer-assisted surgery system (Hisense CAS), thus providing a new global vision and three-dimensional perspective., Methods: We retrospectively collected the clinical data including the diagnoses and treatment processes, of children with UESL confirmed by histopathological examination in our hospital from January 2009 to December 2020. The relationship between the tumour volume and important blood vessels and between the liver volume and tumour volume, as well as other three-dimensional characteristics in the reconstructed three-dimensional model were analysed using Hisense CAS. The findings from this analysis can be used to aid in surgical decision-making and preoperative planning., Results: Four children-3 girls and 1 boy-with UESL were included in the study. The age at onset ranged from 6 to 8 years. All four children presented with symptoms of abdominal discomfort, and abdominal masses were detected during physical examination. Owing to the wishes of their parents and the possibility that the disease was benign, all four children underwent one-stage radical surgery. For patient 1, a three-dimensional reconstruction was created during the initial diagnosis, which made accurate evaluation and planning of the preoperative procedure challenging. In patient 2, the tumour was located in the middle lobe of the liver and involved the first and second hepatic hilum. For patient 3, the pathological diagnosis of the tumour after surgery was challenging, but eventually, the diagnosis was confirmed through histochemistry and consultation with higher-level hospitals. Patient 4 had a giant tumour, which had a preoperative simulated future liver remnant volume (FLV) that was 21.0% of the total volume of the liver and tumour (TLTV). According to the standard liver volume (SLV) for children, the FLV was 77.0% of the SLV, making surgery feasible. All four children underwent complete resection, and only patient 4 experienced recurrence below the diaphragm 19 months after surgery. Currently, the 3-year overall survival rate is 100%, and the 3-year event-free survival rate is 75%., Conclusion: UESL in children is rare, and the key to diagnosis and treatment is complete surgical resection. Through individualized three-dimensional surgical planning, accurate and complete resection of difficult and complex UESL in children can be achieved, leading to a favourable prognosis., (© 2024. The Author(s).)

Polygonatum sibiricum polysaccharide (PSP) was extracted and purified from raw material obtained from P. sibiricum. The structural features of PSP were investigated by Congo red, circular dichroism spectrum, high-performance gel permeation chromatography, scanning electron microscope, atomic force microscope, ultraviolet spectroscopy, and Fourier transform infrared spectroscopy analysis. In vitro simulations were conducted to investigate the kinetics of PSP enzyme inhibition. Moreover, a type II diabetes mouse model (T2DM) with streptozotocin-induced insulin resistance was established, and the indexes of lipid quadruple, insulin resistance index, oral glucose tolerance (OGTT), organ index, and pancreatic morphology of model mice were measured. The results showed that PSP mainly consists of monosaccharides, such as mannose, glucose, galactose, xylose, and arabinose. It also has a β-glycosidic bond of a pyranose ring and an irregular reticulated aggregated structure with a triple helix. In vitro enzyme inhibition assays revealed that PSP acts as a reversible competitive inhibitor of α-glucosidase and α-amylase. Furthermore, PSP was found to reduce insulin resistance index, increase OGTT and serum insulin levels, decrease free fatty acid content to improve lipid metabolism, and lower glycated serum protein content to enhance glucose metabolism in T2DM mice, thereby leading to a reduction in blood glucose concentration. Additionally, PSP exhibited reparative effects on the damaged liver tissue cells and pancreatic tissue in T2DM mice. The experiment results provide a preliminary basis for the therapeutic mechanism of PSP about type II diabetes and a theoretical reference for application in food and pharmaceutical development., (© 2024 Institute of Food Technologists.)

Antimicrobial phototherapy has gained recognition as a promising approach for addressing bacterial biofilms, however, its effectiveness is often impeded by the robust physical and chemical defenses of the biofilms. Traditional antibacterial nanoplatforms face challenges in breaching the extracellular polymeric substances barrier to efficiently deliver photosensitizers deep into biofilms. Moreover, the prevalent hypoxia within biofilms restricts the success of oxygen-reliant phototherapy. In this study, we engineered a soft mesoporous organosilica nanoplatform (SMONs) by incorporating polyethylene glycol (PEG), catalase (CAT), and indocyanine green (ICG), forming SMONs-PEG-CAT-ICG (SPCI). We compared the antimicrobial efficacy of SPCI with more rigid nanoplatforms. Our results demonstrated that unique flexible mechanical properties of SPCI enable it to navigate through biofilm barriers, markedly enhancing ICG penetration in methicillin-resistant Staphylococcus aureus (MRSA) biofilms. Notably, in a murine subcutaneous MRSA biofilm infection model, SPCI showed superior biofilm penetration and pharmacokinetic benefits over its rigid counterparts. The embedded catalase in SPCI effectively converts excess H 2 O 2 present in infected tissues into O 2 , alleviating hypoxia and significantly boosting the antibacterial performance of phototherapy. Both in vitro and in vivo experiments confirmed that SPCI surpasses traditional rigid nanoplatforms in overcoming biofilm barriers, offering improved treatment outcomes for infections associated with bacterial biofilms. This study presents a viable strategy for managing bacterial biofilm-induced diseases by leveraging the unique attributes of a soft mesoporous organosilica-based nanoplatform. STATEMENT OF SIGNIFICANCE: This research introduces an innovative antimicrobial phototherapy soft nanoplatform that overcomes the inherent limitations posed by the protective barriers of bacterial biofilms. By soft nanoplatform with flexible mechanical properties, we enhance the penetration and delivery of photosensitizers into biofilms. The inclusion of catalase within this soft nanoplatform addresses the hypoxia in biofilms by converting hydrogen peroxide into oxygen in infected tissues, thereby amplifying the antibacterial effectiveness of phototherapy. Compared to traditional rigid nanoplatforms, this flexible nanoplatform not only promotes the delivery of therapeutic agents but also sets a new direction for treating bacterial biofilm infections, offering significant implications for future antimicrobial therapies., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Despite the increasing preference for minimally invasive surgery for colorectal cancer (CRC), the incidence of prolonged postoperative ileus (PPOI) remains high. Thus, this study aimed to identify risk factors for PPOI in patients with CRC who underwent minimally invasive surgery (MICRS) and to develop a practical nomogram for predicting individual PPOI risk., Methods: A consecutive series of 2368 patients who underwent MICRS between 2013 and 2023 at two tertiary academic centers were retrospectively studied. Using the data from 1895 patients in the training cohort, a multivariable logistic regression model was employed to select significant variables for the construction of a best-fit nomogram. The nomogram was internally and externally validated., Results: PPOI occurred in 9.5% of patients. Six independent risk factors were identified to construct a nomogram: advanced age (OR 1.055, P = 0.002), male sex (OR 2.914, P = 0.011), age-adjusted Charlson comorbidity index ≥ 6 (OR 2.643, P = 0.025), preoperative sarcopenia (OR 0.857, P = 0.02), preoperative prognostic nutritional index (OR 2.206, P = 0.047), and intraoperative fluid overload (OR 2.227, P = 0.045). The AUCs of the model for predicting PPOI in the training and external validation cohorts were 0.887 and 0.838, respectively. The calibration curves demonstrated excellent consistency between the nomogram-predicted and observed probabilities in both cohorts. Individuals with a total nomogram score of < 197 or ≥ 197 were considered to be at low or high risk for PPOI, respectively., Conclusions: The integrated nomogram we developed could provide personalized risk prediction of PPOI after MICRS. This quantification enables surgeons to implement personalized prevention strategies, thereby improving patient outcomes., (© 2024. The Author(s).)

Although natural attenuation is an economic remediation strategy for uranium (U) contamination, the role of organic molecules in driving U natural attenuation in postmining aquifers is not well-understood. Groundwaters were sampled to investigate the chemical, isotopic, and dissolved organic matter (DOM) compositions and their relationships to U natural attenuation from production wells and postmining wells in a typical U deposit (the Qianjiadian U deposit) mined by neutral in situ leaching. Results showed that Fe(II) concentrations and δ 34 S SO4 and δ 18 O SO4 values increased, but U concentrations decreased significantly from production wells to postmining wells, indicating that Fe(III) reduction and sulfate reduction were the predominant processes contributing to U natural attenuation. Microbial humic-like and protein-like components mediated the reduction of Fe(III) and sulfate, respectively. Organic molecules with H/C > 1.5 were conducive to microbe-mediated reduction of Fe(III) and sulfate and facilitated the natural attenuation of dissolved U. The average U attenuation rate was -1.07 mg/L/yr, with which the U-contaminated groundwater would be naturally attenuated in approximately 11.2 years. The study highlights the specific organic molecules regulating the natural attenuation of groundwater U via the reduction of Fe(III) and sulfate.

Implant infections are severe complications in clinical treatment, which often accompany the formation of bacterial biofilms with high antibiotic resistance. Sonodynamic therapy (SDT) is an antibiotic-free method that can generate reactive oxygen species (ROS) to kill bacteria under ultrasound (US) treatment. However, the extracellular polymeric substances (EPS) barrier of bacterial biofilms and the hypoxic microenvironment significantly limit the antibiofilm activity of SDT. In this study, lipid-shelled perfluoropentane (PFP) nanodroplets loaded with gallium protoporphyrin IX (GaPPIX) and oxygen (O 2 ) (LPGO NDs) were developed for the treatment of implant infections. Under US stimulation, LPGO NDs undergo the cavitation effect and disrupt the biofilm structure like bombs due to liquid-gas phase transition. Meanwhile, the LPGO NDs release O 2 and GaPPIX upon US stimulation. The released O 2 can alleviate the hypoxic microenvironment in the biofilm and enhance the ROS formation by GaPPIX for enhanced bacterial killing. In vivo experimental results demonstrate that the LPGO NDs can efficiently treat implant infections of methicillin-resistant Staphylococcus aureus (MRSA) in a mouse model by disrupting the biofilm structure, alleviating hypoxia, and enhancing bacterial killing by SDT. Therefore, this work provides a new multifunctional sonosensitizer to overcome the limitations of SDT for treating implant infections.

The Pseudomonas aeruginosa biofilm in recalcitrant chronic lung infections not only develops high antimicrobial tolerance but also induces an aberrant host inflammatory response. The metabolic condition plays a vital role in both the antimicrobial susceptibility of bacteria and the inflammatory response of immune cells, thereby offering a potential therapeutic target. Herein, we described a metabolic modulation strategy by using ultrasound-responsive liposomal nanoparticles containing a sonosensitizer and a hypoxia-activated prodrug against biofilm-associated chronic lung infections. Under ultrasound stimulation, the sonosensitizer generates antibacterial reactive oxygen species by oxygen consumption. Subsequently, the oxygen consumption-mediated hypoxia not only induces the anaerobic metabolism of bacteria for antibiotic activation but also triggers the glycolysis pathway of immune cells for inflammatory activation. Such metabolic modulation strategy demonstrated efficient therapeutic efficacy for P. aeruginosa biofilm-induced chronic lung infections in mice models and provides a promising way for combating biofilm-associated chronic infections.