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Aims: Temporomandibular disorder can cause degenerative pathological changes by aseptic inflammation in the temporomandibular joint (TMJ). Vitamin D (VD) is known for maintaining calcium homeostasis, and recent studies indicated that VD and the vitamin D receptor (VDR) are important in inflammatory responses. In this study, we explored the anti-inflammatory effect of VD-VDR signaling axis in TMJ pathological degeneration., Main Methods: Mice ablated for Vdr (Vdr -/-res ) were fed with a rescue diet to avoid hypocalcemia. With abnormal mechanical stimulation, unilateral anterior crossbite (UAC) induced temporomandibular disorders in mice. Histological staining, immunohistochemistry staining, and micro-CT analysis were performed to evaluate TMJ pathological changes. To identify the mechanisms in the aseptic inflammatory process, in vitro experiments were conducted on wild-type (WT) and Vdr -/- chondrocytes with compressive mechanical stress loading, and the related inflammatory markers were examined., Key Findings: Vdr -/-res mice did not develop rickets with a high calcium rescue diet. The TMJ cartilage thickness in Vdr -/-res mice was significantly decreased with mechanical stress stimulation compared to WT mice. UAC-induced bone resorption was obvious, and the number of osteoclasts significantly increased in Vdr -/-res mice. The proliferation was inhibited and the gene expression of Il1b, Mmp3, and Mmp13 was significantly increased in Vdr -/- chondrocytes. However, WT chondrocytes showed significantly increased Tnfa gene expression as a response to mechanical stress but not in Vdr -/- chondrocytes., Significance: VD-VDR is crucial in TMJ pathological changes under abnormal mechanical stimulation. Deletion of Vdr exacerbated inflammatory response excluding TNFα, inhibited chondrocyte proliferation, and promoted bone resorption in TMJ., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: Endosialin, also known as tumor endothelial marker1 or CD248, is a transmembrane glycoprotein that is mainly expressed in cancer-associated fibroblasts (CAFs) in hepatocellular carcinoma (HCC). Our previous study has found that endosialin-positive CAFs could recruit and induce the M2 polarization of macrophages in HCC. However, whether they may regulate other types of immune cells to promoting HCC progression is not known., Approach and Results: The growth of both subcutaneous and orthotopic HCC tumors was significantly inhibited in endosialin knockout (EN KO ) mice. Single-cell sequencing and flow cytometry analysis showed that tumor tissues from EN KO mice had increased CD8 + T cell infiltration. Mixed HCC tumor with Hepa1-6 cells and endosialin knockdown fibroblasts also showed inhibited growth and increased CD8 + T cell infiltration. Data from in vitro co-culture assay, chemokine array and antibody blocking assay, RNA-seq and validation experiments showed that endosialin inhibits the phosphorylation and nuclear translocation of STAT1 in CAFs. This inhibition leads to a decrease in CXCL9/10 expression and secretion, resulting in the suppression of CD8 + T cell infiltration. High level of endosialin protein expression was correlated with low CD8 + T infiltration in the tumor tissue of HCC patients. The combination therapy of endosialin antibody and PD-1 antibody showed synergistic antitumor effect compared with either antibody used individually., Conclusions: Endosialin could inhibit CD8 + T cell infiltration by inhibiting the expression and secretion of CXCL9/10 in CAFs, thus promote HCC progression. Combination therapy with endosialin antibody could increase the antitumor effect of PD-1 antibody in HCC, which may overcome the resistance to PD-1 blockade., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

π frameworks, defined as a type of porous supramolecular materials weaved from conjugated molecular units by π-π stacking interactions, provide a new direction in photocatalysis. However, such examples are rarely reported. Herein, we report a supramolecular-nanocage-based π framework constructed from a photoactive Cu(I) complex unit. Structurally, 24 Cu(I) complex units stack together through π-π stacking interactions, forming a truncated octahedral nanocage with sodalite topology. The inner diameter of the nanocage is 2.8 nm. By sharing four open faces, each nanocage connects with four equivalent ones, forming a 3D porous π framework (π-2). π-2 shows good thermal and chemical stability, which can adsorb CO2, iodine, and methyl orange molecules. More importantly, π-2 can serve as a photocatalyst for hydrogen evolution reaction. With ultrafine Pt subnanometer particles (0.9±0.1 nm) incorporated into the nanocages as a co-catalyst, the hydrogen evolution rate reaches a record-high value of 517551 μmol/gPt/h in the absence of any additional photosensitizers. The high photocatalytic activity can be ascribed to the ultrafine size of the Pt particles, as well as the fast electron transfer from π-2 to the highly active Pt upon illumination. π-2 represents the unique stable supramolecular-cage-based π framework with excellent photocatalytic activity., (© 2024 Wiley‐VCH GmbH.)

Hydrogen-bonded organic frameworks (HOFs) are outstanding candidates for photocatalytic hydrogen evolution. However, most of reported HOFs suffer from poor stability and photocatalytic activity in the absence of Pt cocatalyst. Herein, a series of metal HOFs (Co 2 -HOF-X, X=COOMe, Br, tBu and OMe) have been rationally constructed based on dinuclear cobalt complexes, which exhibit exceptional stability in the presence of strong acid (12 M HCl) and strong base (5 M NaOH) for at least 10 days. More impressively, by varying the -X groups of the dinuclear cobalt complexes, the microenvironment of Co 2 -HOF-X can be modulated, giving rise to obviously different photocatalytic H 2 production rates, following the -X group sequence of -COOMe>-Br>-tBu>-OMe. The optimized Co 2 -HOF-COOMe shows H 2 generation rate up to 12.8 mmol g -1 h -1 in the absence of any additional noble-metal photosensitizers and cocatalysts, which is superior to most reported Pt-assisted photocatalytic systems. Experiments and theoretical calculations reveal that the -X groups grafted on Co 2 -HOF-X possess different electron-withdrawing ability, thus regulating the electronic structures of Co catalytic centres and proton activation barrier for H 2 production, and leading to the distinctly different photocatalytic activity., (© 2024 Wiley-VCH GmbH.)

Background: This study aims to conduct a preliminary exploration of the correlation between the oral microbiota of full-term pregnant women and both local placental immunity and the systemic immune system of the mother., Methods: A total of 26 pregnant women participated in this study, with samples collected from oral swabs, placental tissue, and peripheral venous blood. High-throughput sequencing was used to examine the oral microbial community. Flow cytometry was employed to assess immune cells in placental tissue and peripheral venous blood. ELISA and Luminex liquid bead chip technology were utilized to detect cytokines in both placental tissue and peripheral venous blood., Results: In placental tissue, The oral microbial community is primarily negatively correlated with placental CD3+CD4+CD8+T cells and positively correlated with placental IL-5. In the peripheral blood, The oral microbial community is primarily positively correlated with maternal systemic immune parameters, including CD3+CD4+ T cells and the CD4+/CD8+ ratio, as well as positively correlated with peripheral IL-18., Conclusions: The oral microbiota of full-term pregnant women participates in the regulatory function of the maternal immune system. Meanwhile, the oral microbial community may also be an important factor mediating local immune regulation in the placenta., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Delirium, marked by acute cognitive decline, poses a life-threatening issue among older individuals, especially after cardiac surgery, with prevalence ranging from 15 to 80%. Postoperative delirium is linked to increased morbidity and mortality. Although clinical trials suggest preventability, there is limited research on intranasal insulin (INI) for cardiac surgery-related delirium. INI has shown promise in managing cognitive disorders. It rapidly elevates brain hormone levels, enhancing memory even in non-impaired individuals. While effective in preventing delirium in gastrointestinal surgery, its impact after cardiac surgery remains understudied, especially for middle-aged patients., Method: This is a prospective randomized, double-blind, single-center controlled trial. A total of 76 eligible participants scheduled for elective on-pump cardiac surgery will be enrolled and randomly assigned in a 1:1 ratio to either receive Intranasally administered insulin (INI) or intranasally administered normal saline. The primary outcome of our study is the incidence of postoperative delirium (POD). Secondary outcomes include duration of ICU, postoperative hospital length of stay, all in-hospital mortality, the change in MMSE scores pre- and post-operation, and incidence of postoperative cognitive dysfunction at 1 month, 3 months, and 6 months after operation. Moreover, we will subjectively and objectively evaluate perioperative sleep quality to investigate the potential impact of nasal insulin on the development of delirium by influencing sleep regulation., Discussion: Our study will aim to assess the impact of intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing on-pump elective cardiac surgery. If intranasal insulin proves to be more effective, it may be considered as a viable alternative for preventing postoperative delirium., Trial Registration: ChiCTR ChiCTR2400081444. Registered on March 1, 2024., (© 2024. The Author(s).)

Background: HIV-associated pulmonary arterial hypertension (HIV-PAH), a rare and fatal condition within the pulmonary arterial hypertension spectrum, is linked to HIV infection. While ferroptosis, an iron-dependent cell death form, is implicated in various lung diseases, its role in HIVPAH development remains unclear., Methods: Leveraging Gene Expression Omnibus data, we identified differentially expressed genes (DEGs) in pulmonary arterial smooth muscle cells, including HIV-related DEGs (HIV-DEGs) and ferroptosis-related HIV-DEGs (FR-HIV-DEGs). PPI network analysis of FR-HIV-DEGs using CytoHubba in Cytoscape identified hub genes. We conducted functional and pathway enrichment analyses for FR-HIV-DEGs, HIV-DEGs, and hub genes. Diagnostic value assessment of hub genes utilized ROC curve analysis. Key genes were further screened, and external validation was performed. Additionally, we predicted a potential ceRNA regulatory network for key genes., Results: 1372 DEGs were found, of which 228 were HIV-DEGs, and 20 were FR-HIV-DEGs. TP53, IL6, PTGS2, IL1B (downregulated), and PPARG (upregulated) were the five hub genes that were screened. TP53, IL6, and IL1B act as ferroptosis drivers, PTGS2 as a ferroptosis marker, and PPARG as a ferroptosis inhibitor. Enrichment analysis indicated biological processes enriched in "response to oxidative stress" and pathways enriched in "human cytomegalovirus infection." Key genes IL6 and PTGS2 exhibited strong predictive value via ROC curve analysis and external validation. The predicted ceRNA regulatory network identified miRNAs (has-mir-335-5p, has-mir-124-3p) targeting key genes and lncRNAs (XIST, NEAT1) targeting these miRNAs., Conclusion: This study advances our understanding of potential mechanisms in HIV-PAH pathogenesis, emphasizing the involvement of ferroptosis. The findings offer valuable insights for future research in HIV-PAH., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Prostate cancer (PCa) rarely responds to immune-checkpoint blockade (ICB) therapies. Cancer-associated fibroblasts (CAFs) are critical components of the immunologically "cold" tumor microenvironment and are considered a promising target to enhance the immunotherapy response. In this study, we aimed to reveal the mechanisms regulating CAF plasticity to identify potential strategies to switch CAFs from pro-tumorigenic to anti-tumor phenotypes and enhance ICB efficacy in PCa. Integration of four PCa single-cell RNA-sequencing datasets defined pro-tumorigenic and anti-tumor CAFs, and RNA-seq, flow cytometry, and a PCa organoid model demonstrated the functions of two CAF subtypes. Extracellular matrix-associated CAFs (ECM-CAF) promoted collagen deposition and cancer cell progression, and lymphocyte-associated CAFs (Lym-CAF) exhibited an anti-tumor phenotype and induced the infiltration and activation of CD8+ T cells. YAP1 activity regulated the ECM-CAF phenotype, and YAP1 silencing promoted switching to Lym-CAFs. NF-κB p65 was the core transcription factor in the Lym-CAF subset, and YAP1 inhibited nuclear translocation of p65. Selective depletion of YAP1 in ECM-CAFs in vivo promoted CD8+ T-cell infiltration and activation and enhanced the therapeutic effects of anti- PD-1 treatment in PCa. Overall, this study revealed a mechanism regulating CAF identity in PCa and highlighted a therapeutic strategy for altering the CAF subtype to suppress tumor growth and increase sensitivity to ICB.

In proton exchange membrane water electrolysis (PEMWE), the anode oxygen evolution reaction (OER) catalysts rely heavily on the expensive and scarce iridium-based materials. Ruthenium dioxide (RuO2) with lower price and higher OER activity, has been explored for the similar task, but has been restricted by the poor stability. Herein, we developed an anion modification strategy to improve the OER performance of RuO2 in acidic media. The designed multicomponent catalyst based on sulfate anchored on RuO2/MoO3 displays a low overpotential of 190 mV at 10 mA cm-2 and stably operates for 500 hours with a very low degradation rate of 20 μV h-1. When assembled in a PEMWE cell, this catalyst as an anode shows an excellent stability at 500 mA cm-2 for 150 h. Experimental and theoretical results revealed that MoO3 could stabilize sulfate anion on RuO2 surface to suppress its leaching during OER. Such MoO3-anchored sulfate not only reduces the formation energy of *OOH intermediate on RuO2, but also impedes both the surface Ru and lattice oxygen loss, thereby achieving the high OER activity and exceptional durability., (© 2024 Wiley‐VCH GmbH.)

Direct methane conversion to value-added oxygenates under mild conditions with in-depth mechanism investigation has attracted wide interest. Inspired by methane monooxygenase, the K 9 Na 2 Fe(H 2 O) 2 {[γ-SiW 9 O 34 Fe(H 2 O)]} 2 ·25H 2 O polyoxometalate (Fe-POM) with well-defined Fe(H 2 O) 2 sites is synthesized to clarify the key role of Fe species and their microenvironment toward CH 4 photooxidation. The Fe-POM can efficiently drive the conversion of CH 4 to HCOOH with a yield of 1570.0 µmol g POM -1 and 95.8% selectivity at ambient conditions, much superior to that of [Fe(H 2 O)SiW 11 O 39 ] 5- with Fe(H 2 O) active site, [Fe 2 SiW 10 O 38 (OH)] 2 14- and [P 8 W 48 O 184 Fe 16 (OH) 28 (H 2 O) 4 ] 20- with multinuclear Fe-OH-Fe active sites. Single-dispersion of Fe-POM on polymeric carbon nitride (PCN) is facilely achieved to provide single-cluster functionalized PCN with well-defined Fe(H 2 O) 2 site, the HCOOH yield can be improved to 5981.3 µmol g POM -1 . Systemic investigations demonstrate that the (WO) 4 -Fe(H 2 O) 2 can supply Fe═O active center for C-H activation via forming (WO) 4 -Fe a -O t ···CH 4 intermediate, similar to that for CH 4 oxidation in the monooxygenase. This work highlights a promising and facile strategy for single dispersion of ≈1-2 Å metal center with precise coordination microenvironment by uniformly anchoring nanoscale molecular clusters, which provides a well-defined model for in-depth mechanism research., (© 2024 Wiley‐VCH GmbH.)

Few reports exist on one-step enzymatic methods for the simultaneous production of biodiesel and eicosapentaenoic acid ethyl ester (EPA-EE), a high-value pharmaceutical compound. This study aimed to efficiently express Rhizomucor miehei lipase (pRML) in Pichia pastoris X-33 via propeptide mutation and high-copy strain screening. The mutated enzyme was then used to simultaneously catalyze the production of both biodiesel and EPA-EE. The P46N mutation in the propeptide (P46N-pRML) significantly boosted its production, with the four-copy strain increasing enzyme yield by 3.7-fold, reaching 3425 U/mL. Meanwhile, its optimal temperature increased to 45-50 °C, pH expanded to 7.0-8.0, specific activity doubled, K m reduced to one-third, and k cat / K m increased 7-fold. Notably, P46N-pRML efficiently converts Nannochloropsis gaditana oil's eicosapentaenoic acid (EPA). Under optimal conditions, it achieves up to 93% biodiesel and 92% EPA-EE yields in 9 h. Our study introduces a novel, efficient one-step green method to produce both biodiesel and EPA-EE using this advanced enzyme.

The development of low-cost and efficient photocatalysts to achieve water splitting to hydrogen (H 2 ) is highly desirable but remains challenging. Herein, we design and synthesize two porous polymers (Co-Salen-P and Fe-Salen-P) by covalent bonding of salen metal complexes and pyrene chromophores for photocatalytic H 2 evolution. The catalytic results demonstrate that the two polymers exhibit excellent catalytic performance for H 2 generation in the absence of additional noble-metal photosensitizers and cocatalysts. Particularly, the H 2 generation rate of Co-Salen-P reaches as high as 542.5 μmol g -1 h -1 , which is not only 6 times higher than that of Fe-Salen-P but also higher than a large amount of reported Pt-assisted photocatalytic systems. Systematic studies show that Co-Salen-P displays faster charge separation and transfer efficiencies, thereby accounting for the significantly improved photocatalytic activity. This study provides a facile and efficient way to fabricate high-performance photocatalysts for H 2 production.

Purpose: This study aimed to develop an automated Tomotherapy (TOMO) planning method for cervical cancer treatment, and to validate its feasibility and effectiveness., Materials and Methods: The study enrolled 30 cervical cancer patients treated with TOMO at our center. Utilizing scripting and Python environment within the RayStation (RaySearch Labs, Sweden) treatment planning system (TPS), we developed automated planning methods for TOMO and volumetric modulated arc therapy (VMAT) techniques. The clinical manual TOMO (M-TOMO) plans for the 30 patients were re-optimized using automated planning scripts for both TOMO and VMAT, creating automated TOMO (A-TOMO) and automated VMAT (A-VMAT) plans. We compared A-TOMO with M-TOMO and A-VMAT plans. The primary evaluated relevant dosimetric parameters and treatment plan efficiency were assessed using the two-sided Wilcoxon signed-rank test for statistical analysis, with a P-value < 0.05 indicating statistical significance., Results: A-TOMO plans maintained similar target dose uniformity compared to M-TOMO plans, with improvements in target conformity and faster dose drop-off outside the target, and demonstrated significant statistical differences (P +  < 0.01). A-TOMO plans also significantly outperformed M-TOMO plans in reducing V 50Gy , V 40Gy and D mean for the bladder and rectum, as well as D mean for the bowel bag, femoral heads, and kidneys (all P +  < 0.05). Additionally, A-TOMO plans demonstrated better consistency in plan quality. Furthermore, the quality of A-TOMO plans was comparable to or superior than A-VMAT plans. In terms of efficiency, A-TOMO significantly reduced the time required for treatment planning to approximately 20 min., Conclusion: We have successfully developed an A-TOMO planning method for cervical cancer. Compared to M-TOMO plans, A-TOMO plans improved target conformity and reduced radiation dose to OARs. Additionally, the quality of A-TOMO plans was on par with or surpasses that of A-VMAT plans. The A-TOMO planning method significantly improved the efficiency of treatment planning., (© 2024. The Author(s).)

Solar-driven CO 2 reduction and water oxidation to liquid fuels represents a promising solution to alleviate energy crisis and climate issue, but it remains a great challenge for generating CH 3 OH and CH 3 CH 2 OH dominated by multi-electron transfer. Single-cluster catalysts with super electron acceptance, accurate molecular structure, customizable electronic structure and multiple adsorption sites, have led to greater potential in catalyzing various challenging reactions. However, accurately controlling the number and arrangement of clusters on functional supports still faces great challenge. Herein, we develop a facile electrosynthesis method to uniformly disperse Wells-Dawson- and Keggin-type polyoxometalates on TiO 2 nanotube arrays, resulting in a series of single-cluster functionalized catalysts P 2 M 18 O 62 @TiO 2 and PM 12 O 40 @TiO 2 (M=Mo or W). The single polyoxometalate cluster can be distinctly identified and serves as electronic sponge to accept electrons from excited TiO 2 for enhancing surface-hole concentration and promote water oxidation. Among these samples, P 2 Mo 18 O 62 @TiO 2 -1 exhibits the highest electron consumption rate of 1260 μmol g -1 for CO 2 -to-CH 3 OH conversion with H 2 O as the electron source, which is 11 times higher than that of isolated TiO 2 nanotube arrays. This work supplied a simple synthesis method to realize the single-dispersion of molecular cluster to enrich surface-reaching holes on TiO 2 , thereby facilitating water oxidation and CO 2 reduction., (© 2024 Wiley-VCH GmbH.)

Dinuclear metal synergistic catalysis (DMSC) has been proved an effective approach to enhance catalytic efficiency in photocatalytic CO 2 reduction reaction, while it remains challenge to design dinuclear metal complexes that can show DMSC effect. The main reason is that the influence of the microenvironment around dinuclear metal centres on catalytic activity has not been well recognized and revealed. Herein, we report a dinuclear cobalt complex featuring a planar structure, which displays outstanding catalytic efficiency for photochemical CO 2 -to-CO conversion. The turnover number (TON) and turnover frequency (TOF) values reach as high as 14457 and 0.40 s -1 respectively, 8.6 times higher than those of the corresponding mononuclear cobalt complex. Control experiments and theoretical calculations revealed that the enhanced catalytic efficiency of the dinuclear cobalt complex is due to the indirect DMSC effect between two Co II ions, energetically feasible one step two-electron transfer process by Co 2 I,I intermediate to afford Co 2 II,II (CO 2 2- ) intermediate and fast mass transfer closely related with the planar structure., (© 2024 Wiley-VCH GmbH.)

Background: Elevated PPP4C expression has been associated with poor prognostic implications for patients suffering from lung adenocarcinoma (LUAD). The extent to which PPP4C affects immune cell infiltration in LUAD, as well as the importance of associated genes in clinical scenarios, still requires thorough investigation., Methods: In our investigation, we leveraged both single-cell and comprehensive RNA sequencing data, sourced from LUAD patients, in our analysis. This study also integrated datasets of immune-related genes from InnateDB into the framework. Our expansive evaluation employed various analytical techniques; these included pinpointing differentially expressed genes, constructing WGCNA, implementing Cox proportional hazards models. We utilized these methods to investigate the gene expression profiles of PPP4C within the context of LUAD and to clarify its potential prognostic value for patients. Subsequent steps involved validating the observed enhancement of PPP4C expression in LUAD samples through a series of experimental approaches. The array comprised immunohistochemistry staining, Western blotting, quantitative PCR, and a collection of cell-based assays aimed at evaluating the influence of PPP4C on the proliferative and migratory activities of LUAD cells., Results: In lung cancer, elevated expression levels of PPP4C were observed, correlating with poorer patient prognoses. Validation of increased PPP4C levels in LUAD specimens was achieved using immunohistochemical techniques. Experimental investigations have substantiated the role of PPP4C in facilitating cellular proliferation and migration in LUAD contexts. Furthermore, an association was identified between the expression of PPP4C and the infiltration of immune cells in these tumors. A prognostic framework, incorporating PPP4C and immune-related genes, was developed and recognized as an autonomous predictor of survival in individuals afflicted with LUAD. This prognostic tool has demonstrated considerable efficacy in forecasting patient survival and their response to immunotherapeutic interventions., Conclusion: The involvement of PPP4C in LUAD is deeply intertwined with the tumor's immune microenvironment. PPP4C's over-expression is associated with negative clinical outcomes, promoting both tumor proliferation and spread. A prognostic framework based on PPP4C levels may effectively predict patient prognoses in LUAD, as well as the efficacy of immunotherapy strategy. This research sheds light on the mechanisms of immune interaction in LUAD and proposes a new strategy for treatment., 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 Wang, Peng, Xu, Lu, Chang, Shen, Shi, Li, Wang, Zhou, Xu, Chang and Zhang.)

Background: SLC30A5, a member of the solute transporter protein family, is implicated in tumorigenesis and cancer progression. This study aimed to explore the expression and prognostic significance of SLC30A family genes in pan-cancer, with a specific emphasis on SLC30A5 in hepatocellular carcinoma (HCC). Methods: Expression patterns and prognostic implications of SLC30A family genes were assessed across 33 cancer types, especially HCC. Co-expression analysis explored the relationship between SLC30A5 and immune cell infiltration, immune checkpoints, pathway molecules related to tumor angiogenesis and epithelial-mesenchymal transition (EMT). The role of SLC30A5 in HCC was evaluated through in vitro and in vivo assays, including CCK8 viability assay, EdU cell proliferation assay, colony formation assay, apoptosis assay, wound healing assay, transwell migration assay, and xenograft mouse model assay using Huh7 cells with targeted knockdown of SLC30A5. Results: SLC30A family genes exhibited overexpression in various tumors. In HCC, upregulation of SLC30A5 expression correlated with adverse prognosis. Significant associations were observed between SLC30A5 expression and immune cell infiltration, immune checkpoints, molecules involved in angiogenesis, and EMT. SLC30A5 overexpression was associated with advanced disease stages, higher histological grades, and vascular invasion. Single-cell RNA sequencing data (GSE112271) revealed notable SLC30A5 expression in malignant cells. In vitro and in vivo assays demonstrated that SLC30A5 knockdown in Huh7 cells reduced proliferation, migration, and invasion while promoting apoptosis. Conclusions: This study highlights the clinical relevance of SLC30A5 in HCC, emphasizing its role in cell proliferation and migration. SLC30A5 emerges as a promising candidate for a prognostic marker and a potential target in HCC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: The presence of lymph node (LN) metastasis directly affects the treatment strategy for lung adenocarcinoma (LUAD). Next-generation sequencing (NGS) has been widely used in patients with advanced LUAD to identify targeted genes, while early detection of pathologic LN metastasis using NGS has not been assessed., Methods: Clinicopathologic features and molecular characteristics of 224 patients from Ruijin Hospital were analyzed to detect factors associated with LN metastases. Another 140 patients from Huashan Hospital were set as a test cohort., Results: Twenty-four out of 224 patients were found to have lymph node metastases (10.7%). Pathologic LN-positive tumors showed higher mutant allele tumor heterogeneity (p < 0.05), higher tumor mutation burden (p < 0.001), as well as more frequent KEAP1 (p = 0.001), STK11 (p = 0.004), KRAS (p = 0.007), CTNNB1 (p = 0.017), TP53, and ARID2 mutations (both p = 0.02); whereas low frequency of EGFR mutation (p = 0.005). A predictive nomogram involving male sex, solid tumor morphology, higher T stage, EGFR wild-type, and TP53, STK11, CDKN2A, KEAP1, ARID2, KRAS, SDHA, SPEN, CTNNB1, DICER1 mutations showed outstanding efficiency in both the training cohort (AUC = 0.819) and the test cohort (AUC = 0.780)., Conclusion: This study suggests that the integration of genomic profiling and clinical features identifies early-invasive LUAD patients at higher risk of LN metastasis. Improved identification of LN metastasis is beneficial for the optimization of the patient's therapy decisions., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

The construction of secondary building units (SBUs) in versatile metal-organic frameworks (MOFs) represents a promising method for developing multi-functional materials, especially for improving their sensitizing ability. Herein, we developed a dual small molecules auxiliary strategy to construct a high-nuclear transition-metal-based UiO-architecture Co 16 -MOF-BDC with visible-light-absorbing capacity. Remarkably, the N 3 - molecule in hexadecameric cobalt azide SBU offers novel modification sites to precise bonding of strong visible-light-absorbing chromophores via click reaction. The resulting Bodipy@Co 16 -MOF-BDC exhibits extremely high performance for oxidative coupling benzylamine (~100 % yield) via both energy and electron transfer processes, which is much superior to that of Co 16 -MOF-BDC (31.5 %) and Carboxyl @Co 16 -MOF-BDC (37.5 %). Systematic investigations reveal that the advantages of Bodipy@Co 16 -MOF-BDC in dual light-absorbing channels, robust bonding between Bodipy/Co 16 clusters and efficient electron-hole separation can greatly boost photosynthesis. This work provides an ideal molecular platform for synergy between photosensitizing MOFs and chromophores by constructing high-nuclear transition-metal-based SBUs with surface-modifiable small molecules., (© 2024 Wiley-VCH GmbH.)

Background: Postoperative urinary tract infection is a common complication that not only significantly prolongs the hospital stay and amplifies the economic burden on patients, but also affects their quality of life and prognosis. This study aimed to investigate risk factors and distribution of pathogenic bacteria in urinary tract infections among bladder cancer patients who underwent cutaneous ureterostomy following radical cystectomy., Methods: A total of 137 bladder cancer patients, who underwent cutaneous ureterostomy after radical cystectomy at our hospital from November 2018 to October 2022, were enrolled in this retrospective study. Univariate and multivariate logistic regression analyses were employed to investigate the risk factors associated with postoperative urinary tract infection and the distribution of pathogenic bacteria among the infected patients., Results: The results of both univariate and multivariate analyses confirmed that age, proficiency in ostomy knowledge, frequency of ureteral stent tube replacement, ureteral stent tube dislodgement, urine immersion at the outer end of the ureteral stent tube, and the interval of ostomy bag replacement were independent risk factors for urinary tract infection after radical cystectomy and cutaneous ureterostomy in bladder cancer patients. A total of 55 pathogenic bacteria were isolated from 52 patients with infections. Predominantly, these were gram-negative bacteria (34 strains, 61.8%), with Proteus mirabilis having the highest proportion., Conclusion: Urinary tract infections after radical cystectomy and cutaneous ureterostomy predominantly involve gram-negative bacteria. This is correlated with factors such as the age of bladder cancer patients, the level of nursing education, the duration of ureteral stent tubes and ostomy bag usage, as well as issues related to impaired urine drainage., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Necrosis in solid tumors is commonly associated with poor prognostic but how these lesions expand remains unclear. Studies have found that neutrophils associate with and contribute to necrosis development in glioblastoma by inducing tumor cell ferroptosis through transferring myeloperoxidase-containing granules. However, the mechanism of neutrophilic granule transfer remains elusive. We performed an unbiased small molecule screen and found that statins inhibit neutrophil-induced tumor cell death by blocking the neutrophilic granule transfer. Further, we identified a novel process wherein neutrophils are engulfed by tumor cells before releasing myeloperoxidase-containing contents into tumor cells. This neutrophil engulfment is initiated by integrin-mediated adhesion, and further mediated by LC3-associated phagocytosis (LAP), which can be blocked by inhibiting the Vps34-UVRAG-RUBCN-containing PI3K complex. Myeloperoxidase inhibition or Vps34 depletion resulted in reduced necrosis formation and prolonged mouse survival in an orthotopic glioblastoma mouse model. Thus, our study unveils a critical role for LAP-mediated neutrophil internalization in facilitating the transfer of neutrophilic granules, which in turn triggers tumor cell death and necrosis expansion. Targeting this process holds promise for improving glioblastoma prognosis., (© 2024. The Author(s).)

Apolipoprotein E ε4 (APOE4) is a strong genetic risk factor of Alzheimer's disease and metabolic dysfunction. However, whether APOE4 and markers of metabolic dysfunction synergistically impact the deterioration of white matter (WM) integrity in older adults remains unknown. In the UK Biobank data, we conducted a multivariate analysis to investigate the interactions between APOE4 and 249 plasma metabolites (measured using nuclear magnetic resonance spectroscopy) with whole-brain WM integrity (measured by diffusion-weighted magnetic resonance imaging) in a cohort of 1917 older adults (aged 65.0-81.0 years; 52.4 % female). Although no main association was observed between either APOE4 or metabolites with WM integrity (adjusted P > 0.05), significant interactions between APOE4 and metabolites with WM integrity were identified. Among the examined metabolites, higher concentrations of low-density lipoprotein and very low-density lipoprotein were associated with a lower level of WM integrity (b=-0.12, CI=-0.14,-0.10) among APOE4 carriers. Conversely, among non-carriers, they were associated with a higher level of WM integrity (b=0.05, CI=0.04,0.07), demonstrating a significant moderation role of APOE4 (b =-0.18, CI=-0.20,-0.15, P<0.00001)., Competing Interests: Declaration of Competing Interest The authors declare that this manuscript, in its entirety or in part, has not been previously published or is under consideration for publication elsewhere, in any language. Each author acknowledges their responsibility for the content presented. Furthermore, the authors affirm that, if accepted, the manuscript will not be reproduced or published in the same form, whether in English or any other language, including electronic formats, without obtaining written consent from the copyright-holder. This submission adheres to ethical standards, and the authors stand committed to exclusive publication rights for the work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ferroptosis, an iron-dependent form of non-apoptotic regulated cell death, is induced by the accumulation of lipid peroxides on cellular membranes. Over the past decade, ferroptosis has emerged as a crucial process implicated in various physiological and pathological systems. Positioned as an alternative modality of cell death, ferroptosis holds promise for eliminating cancer cells that have developed resistance to apoptosis induced by conventional therapeutics. This has led to a growing interest in leveraging ferroptosis for cancer therapy across diverse malignancies. Gliomas are tumors arising from glial or precursor cells, with glioblastoma (GBM) being the most common malignant primary brain tumor that is associated with a dismal prognosis. This review provides a summary of recent advancements in the exploration of ferroptosis-sensitizing methods, with a specific focus on their potential application in enhancing the treatment of gliomas. In addition to summarizing the therapeutic potential, this review also discusses the intricate interplay of ferroptosis and its potential tumor-promoting roles within gliomas. Recognizing these dual roles is essential, as they could potentially complicate the therapeutic benefits of ferroptosis. Exploring strategies aimed at circumventing these tumor-promoting roles could enhance the overall therapeutic efficacy of ferroptosis in the context of glioma treatment., 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.)

Background: The Spike protein mutation severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to decreased protective effect of various vaccines and mAbs, suggesting that blocking SARS-CoV-2 infection by targeting host factors would make the therapy more resilient against virus mutations. Angiotensin-converting enzyme 2 (ACE2) is the host receptor of SARS-CoV-2 and its variants, as well as many other coronaviruses. Downregulation of ACE2 expression in the respiratory tract may prevent viral infection. Antisense oligonucleotides (ASOs) can be rationally designed on the basis of sequence data, require no delivery system, and can be administered locally., Objective: We sought to design ASOs that can block SARS-CoV-2 by downregulating ACE2 in human airway., Methods: ACE2-targeting ASOs were designed using a bioinformatic method and screened in cell lines. Human primary nasal epithelial cells cultured at the air-liquid interface and humanized ACE2 mice were used to detect the ACE2 reduction levels and the safety of ASOs. ASO-pretreated nasal epithelial cells and mice were infected and then used to detect the viral infection levels., Results: ASOs reduced ACE2 expression on mRNA and protein level in cell lines and in human nasal epithelial cells. Furthermore, they efficiently suppressed virus replication of 3 different SARS-CoV-2 variants in human nasal epithelial cells. In vivo, ASOs also downregulated human ACE2 in humanized ACE2 mice and thereby reduced viral load, histopathologic changes in lungs, and increased survival of mice., Conclusions: ACE2-targeting ASOs can effectively block SARS-CoV-2 infection. Our study provides a new approach for blocking SARS-CoV-2 and other ACE2-targeting virus in high-risk populations., Competing Interests: Disclosure statement This study was supported by Guangdong Research Program of Key Fields grant, National Natural Science Foundation of China grants, Natural Science Foundation of Guangdong Province grants, and Guangzhou Science and Technology Project of China grant. Disclosure of potential conflict of interest: The authors have filed patent applications for human angiotensin-converting enzyme 2–targeting antisense oligonucleotides and their activities in inhibiting severe acute respiratory syndrome coronavirus 2 infection., (Copyright © 2024. Published by Elsevier Inc.)

Background: Despite the large patient base in Asia, the prognostic factors of patients with non-eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) remain largely undetermined., Objective: We aimed to systematically investigate the predictive value of clinical and biological variables for non-eosinophilic CRSwNP., Methods: Fifty-one patients with non-eosinophilic CRSwNP who underwent functional endoscopic surgery were recruited. Clinical information and assessment were comprehensively collected before and after surgery. A broad spectrum of biomarkers was measured in tissue homogenates using multiple assays. A random forest algorithm and stepwise logistic regression were used to construct clinical, biological, and combined models., Results: A total of 41.2% of non-eosinophilic CRSwNP patients were uncontrolled more than 6 months after surgery. We identified one clinical variable (22-item Sino-Nasal Outcome Test score) and four biomarkers (programmed cell death ligand 1, platelet-derived growth factor subunit B [PDGF-β], macrophage inflammatory protein-3b, and PDGF-α) that were significantly predictive of the surgical outcome. The clinical, biological, and combined models showed predictive ability with areas under the curve of 0.78, 0.83, and 0.89, respectively. PDGF-β and programmed cell death ligand 1 were identified as independent biomarkers for the prognosis of patients with CRSwNP without considerable eosinophilic infiltration., Conclusion: This study shows that clinical and biological factors, such as the 22-item Sino-Nasal Outcome Test score and PDGF-β, are predictive of the post-functional endoscopic surgical prognosis of non-eosinophilic CRSwNP patients., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To investigate the prevalence of subthreshold depression among Chinese college students and to explore the related factors., Methods: The research subjects were Chinese college students participating in the "2022 Psychology and Behavior Investigation of Chinese Residents (PBICR-2022)". Data on respondents' general characteristics, quality of life, perceived pressure, family communication, perceived social support, self-efficacy, and depression status were gathered. To investigate the association between each variable and the risk of subthreshold depression, statistical analyses, including chi-square tests and rank sum tests were conducted. Furthermore, a binary stepwise logistic regression was employed to establish the regression model of the factors related to subthreshold depression among Chinese college students., Results: A prevalence of subthreshold depression of about 39.7 % was found among the 8934 respondents. Logistic regression analysis revealed that respondents who are female, have chronic diseases, are in debt, experience significant impacts from epidemic control policies, have lower self-assessed quality of life, experience challenges in family communication, perceive lower social support, have lower self-efficacy, and feel higher perceived pressure are more likely to develop subthreshold depression compared to the control group. (P < 0.05)., Conclusion: The prevalence rate of subthreshold depression among Chinese college students was found to be approximately 40 %. Female college students suffering from chronic diseases, with households in debt, greatly impacted by epidemic control policies, and experiencing high perceived stress, may be at risk for subthreshold depression among Chinese college students. On the other hand, strong family communication, perceived social support, and self-efficacy were identified as potential protective factors. In order to facilitate timely screening, diagnosis, and treatment of subthreshold depression in Chinese college students, it is crucial for the government, local communities, colleges, and families to prioritize the mental health of college students and implement targeted measures accordingly., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Glymphatic dysfunction has been correlated with cognitive decline, with a higher choroid plexus volume (CPV) being linked to a slower glymphatic clearance rate. Nevertheless, the interplay between CPV, glymphatic function, and cognitive impairment in white matter hyperintensities (WMHs) has not yet been investigated. In this study, we performed neuropsychological assessment, T1-weighted three-dimensional (3D-T1) images, and diffusion tensor imaging (DTI) in a cohort of 206 WMHs subjects and 43 healthy controls (HCs) to further explore the relationship. The DTI analysis along the perivascular space (DTI-ALPS) index, as a measure of glymphatic function, was calculated based on DTI. Severe WMHs performed significantly worse in information processing speed (IPS) than other three groups, as well as in executive function than HCs and mild WMHs. Additionally, severe WMHs demonstrated lower DTI-ALPS index and higher CPV than HCs and mild WMHs. Moderate WMHs displayed higher CPV than HCs and mild WMHs. Mini-Mental State Examination, IPS, and executive function correlated negatively with CPV but positively with DTI-ALPS index in WMHs patients. Glymphatic function partially mediated the association between CPV and IPS, indicating a potential mechanism for WMHs-related cognitive impairment. CPV may act as a valuable prognostic marker and glymphatic system as a promising therapeutic target for WMHs-related cognitive impairment., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Polatuzumab vedotin is a CD79b-directed antibody-drug conjugate that targets B cells and delivers the cytotoxic payload monomethyl auristatin E (MMAE). The phase III POLARIX study (NCT03274492) evaluated polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) as first-line treatment of diffuse large B-cell lymphoma (DLBCL). To examine dosing decisions for this regimen, population pharmacokinetic (popPK) analysis, using a previously developed popPK model, and exposure-response (ER) analysis, were performed. The popPK analysis showed no clinically meaningful relationship between cycle 6 (C6) antibody-conjugated (acMMAE)/unconjugated MMAE area under the concentration-time curve (AUC) or maximum concentration, and weight, sex, ethnicity, region, mild or moderate renal impairment, mild hepatic impairment, or other patient and disease characteristics. In the ER analysis, C6 acMMAE AUC was significantly associated with longer progression-free and event-free survival (both p = 0.01). An increase of <50% in acMMAE/unconjugated MMAE exposure did not lead to a clinically meaningful increase in adverse events of special interest. ER data and the benefit-risk profile support the use of polatuzumab vedotin 1.8 mg/kg once every 3 weeks with R-CHP for six cycles in patients with previously untreated DLBCL., (© 2024 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

The development of high-performance photocatalytic systems for CO 2 reduction is appealing to address energy and environmental issues, while it is challenging to avoid using toxic metals and organic sacrificial reagents. We here immobilize a family of cobalt phthalocyanine catalysts on Pb-free halide perovskite Cs 2 AgBiBr 6 nanosheets with delicate control on the anchors of the cobalt catalysts. Among them, the molecular hybrid photocatalyst assembled by carboxyl anchors achieves the optimal performance with an electron consumption rate of 300±13 μmol g -1  h -1 for visible-light-driven CO 2 -to-CO conversion coupled with water oxidation to O 2 , over 8 times of the unmodified Cs 2 AgBiBr 6 (36±8 μmol g -1  h -1 ), also far surpassing the documented systems (<150 μmol g -1  h -1 ). Besides the improved intrinsic activity, electrochemical, computational, ex-/in situ X-ray photoelectron and X-ray absorption spectroscopic results indicate that the electrons photogenerated at the Bi atoms of Cs 2 AgBiBr 6 can be directionally transferred to the cobalt catalyst via the carboxyl anchors which strongly bind to the Bi atoms, substantially facilitating the interfacial electron transfer kinetics and thereby the photocatalysis., (© 2024 Wiley-VCH GmbH.)

The reaction kinetics of photocatalytic CO 2 reduction is highly dependent on the transfer rate of electrons and protons to the CO 2 molecules adsorbed on catalytic centers. Studies on uncovering the proton effect in catalysts on photocatalytic activity of CO 2 reduction are significant but rarely reported. In this paper, we, from the molecular level, revealed that the photocatalytic activity of CO 2 reduction is closely related to the proton availability in catalysts. Specifically, four dinuclear Co(II) complexes based on Robson-type ligands with different number of carboxylic groups (- n COOH; n = 0, 2, 4, 6) were designed and synthesized. All these complexes show photocatalytic activity for CO 2 reduction to CO in a water-containing system upon visible-light illumination. Interestingly, the CO yields increase positively with the increase of the carboxylic-group number in dinuclear Co(II) complexes. The one containing -6COOH shows the best photocatalytic activity for CO 2 reduction to CO, with the TON value reaching as high as 10,294. The value is 1.8, 3.4, and 7.8 times higher than those containing -4COOH, -2COOH, and -0COOH, respectively. The high TON value also makes the dinuclear Co(II) complex with -6COOH outstanding among reported homogeneous molecular catalysts for photocatalytic CO 2 reduction. Control experiments and density functional theory calculation indicated that more carboxylic groups in the catalyst endow the catalyst with more proton relays, thus accelerating the proton transfer and boosting the photocatalytic CO 2 reduction. This study, at a molecular level, elucidates that more carboxylic groups in catalysts are beneficial for boosting the reaction kinetics of photocatalytic CO 2 reduction., Competing Interests: Competing interests statement:The authors declare no competing interest.

Allergic airway inflammation (AAI), including allergic rhinitis (AR) and allergic asthma, is driven by epithelial barrier dysfunction and type 2 inflammation. However, the underlying mechanism remains uncertain and available treatments are constrained. Consequently, we aim to explore the role of cell-free DNA (cfDNA) in AAI and assess the potential alleviating effects of cationic polymers (CPs) through cfDNA elimination. Levels of cfDNA were evaluated in AR patients, allergen-stimulated human bronchial epithelium (BEAS-2B cells) and primary human nasal epithelium from both AR and healthy control (HC), and AAI murine model. Polyamidoamine dendrimers-generation 3 (PAMAM-G3), a classic type of cationic polymers, were applied to investigate whether the clearance of cfDNA could ameliorate airway epithelial dysfunction and inhibit AAI. The levels of cfDNA in the plasma and nasal secretion from AR were higher than those from HC (P < 0.05). Additionally, cfDNA levels in the exhaled breath condensate (EBC) were positively correlated with Interleukin (IL)-5 levels in EBC (R = 0.4191, P = 0.0001). Plasma cfDNA levels negatively correlated with the duration of allergen immunotherapy treatment (R = -0.4297, P = 0.006). Allergen stimulated cfDNA secretion in vitro (P < 0.001) and in vivo (P < 0.0001), which could be effectively scavenged with PAMAM-G3. The application of PAMAM-G3 inhibited epithelial barrier dysfunction in vitro and attenuated the development of AAI in vivo. This study elucidates that cfDNA, a promising biomarker for monitoring disease severity, aggravates AAI and the application of intranasal PAMAM-G3 could potentially be a novel therapeutic intervention for AAI. Allergen stimulates the secretion of cell-free DNA (cfDNA) in both human and mouse airway. Intranasal polyamidoamine dendrimers-generation 3 (PAMAM-G3) scavenges cfDNA and alleviates allergic airway inflammation., (© 2024. The Author(s).)

The therapeutic outcomes of patients with eosinophilic chronic rhinosinusitis (ECRS) remain unsatisfactory, largely because the underlying mechanisms of eosinophilic inflammation are uncertain. Here, it is shown that the nasal secretions of ECRS patients have high eosinophil extracellular trap (EET) and cell-free DNA (cfDNA) levels. Moreover, the cfDNA induced EET formation by activating toll-like receptor 9 (TLR9) signaling. After demonstrating that DNase I reduced eosinophilic inflammation by modulating EET formation, linear polyglycerol-amine (LPG A )-coated TiS 2 nanosheets (TLPG A ) as functional 2D nanoplatforms with low cytotoxicity, mild protein adsorption, and increased degradation rate is developed. Due to the more flexible linear architecture, TLPG A exhibited higher cfDNA affinity than the TiS 2 nanosheets coated with dendritic polyglycerol-amine (TDPG A ). TLPG A reduced cfDNA levels in the nasal secretions of ECRS patients while suppressing cfDNA-induced TLR9 activation and EET formation in vitro. TLPG A displayed exceptional biocompatibility, preferential nasal localization, and potent inflammation modulation in mice with eosinophilic inflammation. These results highlight the pivotal feature of the linear molecular architecture and 2D sheet-like nanostructure in the development of anti-inflammation nanoplatforms, which can be exploited for ECRS treatment., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: Ultrasonic scalpel has been reported to be superior to conventional electrocautery in many studies. However, with respect to transaxillary endoscopic breast augmentation, few studies on the effect of ultrasonic scalpel are available in the literature., Methods: The medical records of 173 female patients who underwent breast augmentation via endoscopic transaxillary approach from January 2018 to December 2020 were reviewed retrospectively. The patients were divided into two groups according to the implant pocket dissection instruments. In group A, the implant pockets were dissected with conventional electrocautery (EC group) on 81 patients, and in group B, ultrasonic scalpel (US group) was used for implant pockets on 92 patients. All operations were performed by the same senior plastic surgeon and the same surgical team. The operation time, intraoperative blood loss, postoperative total drainage volume, days of drainage, postoperative surgical site pain and hospital stay time of the two groups were compared and analyzed statistically., Results: The average operation time of the US group (83.82 ± 11.57 min) was significantly shorter than that of the EC group (101.40 ± 14.36 min), intraoperative blood loss in the US group was significantly less than that of the EC group (18.67 ± 6.20 ml vs. 21.59 ± 6.44 ml), the mean hospital stay days (2.96 ± 0.69 vs. 4.30 ± 1.11), total drainage volume (122.24 ± 43.81 vs. 232.37 ± 99.15), and duration of drain (2.52 ± 0.54 vs. 3.77 ± 1.10), mean VAS score for surgical site pain on 3 postoperative days (5.08 ± 1.35 vs. 6.51 ± 1.36, 4.08 ± 1.16 vs. 5.40 ± 1.32, 3.04 ± 0.91 vs. 4.06 ± 1.11) were significantly lower in the US group compared to the EC group., Conclusions: The ultrasonic scalpel reduces operative time, intraoperative blood loss, postoperative drainage, postoperative pain, hospital stay time, and incidence of complications. The ultrasonic scalpel is safe and reliable for transaxillary endoscopic breast augmentation., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

The rising sentiment challenges of the metropolitan residents may be attributed to the extreme temperatures. However, nationwide real-time empirical studies that examine this claim are rare. In this research, we construct a daily extreme temperature index and sentiment metric using geotagged posts on one of China's largest social media sites, Weibo, to verify this hypothesis. We find that extreme temperatures causally decrease individuals' sentiment, and extremely low temperature may decrease more than extremely high temperature. Heterogeneity analyses reveal that individuals living in high levels of PM2.5, existing new COVID-19 diagnoses and low-disposable income cities on workdays are more vulnerable to the impact of extreme temperatures on sentiment. More importantly, the results also demonstrate that the adverse effects of extremely low temperatures on sentiment are more minor for people living in northern cities with breezes. Finally, we estimate that with a one-standard increase of extremely high (low) temperature, the sentiment decreases by approximately 0.161 (0.272) units. Employing social media to monitor public sentiment can assist policymakers in developing data-driven and evidence-based policies to alleviate the adverse impacts of extreme temperatures., (© 2024. The Author(s).)

The vertical profiles of aerosol or mixed-phase cloud optical properties (e.g. extinction coefficient) at 1064 nm are difficult to obtain from lidar observations. Based on the techniques of rotational Raman signal at 1058 nm described by Haarig et al. [Atmos. Meas. Tech.9, 4269 (2016)10.5194/amt-9-4269-2016], we have developed a novel rotational Raman polarization lidar at 1064 nm at Wuhan University. In this design, we optimized the central wavelength of the rotational Raman channel to 1056 nm with a bandwidth of 6 nm to increase the signal-to-noise ratio and minimize the temperature dependence of the extracted rotational Raman spectrum. And then separated elastic polarization channels (1064 nm Parallel, P and 1064 nm Cross, S) into near range (low 1064 nm P and 1064 nm S) and far range detection channels (high 1064 nm P and 1064 nm S) to extend the dynamic range of lidar observation. Silicon single photon avalanche diodes (SPAD) working at photon counting mode were applied to improve the quantum efficiency and reduce the electronic noise, which resulted in quantum efficiency of 2.5%. With a power of 3 W diode pumped pulsed Nd:YAG laser and aperture of 250 mm Cassegrain telescope, the detectable range can cover the atmosphere from 0.3 km to the top troposphere (about 12-15 km). To the best of our knowledge, the design of this novel lidar system is described and the mixed-phase cloud and aerosol optical properties observations of backscatter coefficients, extinction coefficients, lidar ratio and depolarization ratio at 1064 nm were performed as demonstrations of the system capabilities.

Objective: Gastric cancer is a prevalent gastrointestinal malignancy worldwide. In this study, a prognostic model was developed for gastric cancer patients who underwent radical gastrectomy using machine learning, employing advanced computational techniques to investigate postoperative mortality risk factors in such patients., Methods: Data of 295 patients with gastric cancer who underwent radical gastrectomy at the Department of General Surgery of Affiliated Hospital of Xuzhou Medical University (Xuzhou, China) between March 2016 and November 2019 were retrospectively analyzed as the training group. Additionally, 109 patients who underwent radical gastrectomy at the Department of General Surgery Affiliated to Jining First People's Hospital (Jining, China) were included for external validation. Four machine learning models, including logistic regression (LR), decision tree (DT), random forest (RF), and gradient boosting machine (GBM), were utilized. Model performance was assessed by comparing the area under the curve (AUC) for each model. An LR-based nomogram model was constructed to assess patients' clinical prognosis., Results: Lasso regression identified eight associated factors: age, sex, maximum tumor diameter, nerve or vascular invasion, TNM stage, gastrectomy type, lymphocyte count, and carcinoembryonic antigen (CEA) level. The performance of these models was evaluated using the AUC. In the training group, the AUC values were 0.795, 0.759, 0.873, and 0.853 for LR, DT, RF, and GBM, respectively. In the validation group, the AUC values were 0.734, 0.708, 0.746, and 0.707 for LR, DT, RF, and GBM, respectively. The nomogram model, constructed based on LR, demonstrated excellent clinical prognostic evaluation capabilities., Conclusion: Machine learning algorithms are robust performance assessment tools for evaluating the prognosis of gastric cancer patients who have undergone radical gastrectomy. The LR-based nomogram model can aid clinicians in making more reliable clinical decisions., 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. The handling editor, QZ, declared a shared parent affiliation with the author ML at the time of review., (Copyright © 2024 Lu, Lu, Liu, Song, Wang, Guo, Fang, Chen and Li.)

Extracellular vesicles (EVs) can deliver various bioactive molecules among cells, making them promising diagnostic and therapeutic alternatives in diseases. Mesenchymal stem cell-derived EVs (MSC-EVs) have shown therapeutic potential similar to MSCs but with drawbacks such as lower yield, reduced biological activities, off-target effects, and shorter half-lives. Improving strategies utilizing biotechniques to pretreat MSCs and enhance the properties of released EVs, as well as modifying MSC-EVs to enhance targeting abilities and achieve controlled release, shows potential for overcoming application limitations and enhancing therapeutic effects in treating bone-related diseases. This review focuses on recent advances in functionalizing MSC-EVs to treat bone-related diseases. Firstly, we underscore the significance of MSC-EVs in facilitating crosstalk between cells within the skeletal environment. Secondly, we highlight strategies of functional-modified EVs for treating bone-related diseases. We explore the pretreatment of stem cells using various biotechniques to enhance the properties of resulting EVs, as well as diverse approaches to modify MSC-EVs for targeted delivery and controlled release. Finally, we address the challenges and opportunities for further research on MSC-EVs in bone-related diseases., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Wang et al.)

The development of strong sensitizing and Earth-abundant antenna molecules is highly desirable for CO 2 reduction through artificial photosynthesis. Herein, a library of Zn-dipyrrin complexes ( Z-1 - Z-6 ) are rationally designed via precisely controlling their molecular configuration to optimize strong sensitizing Earth-abundant photosensitizers. Upon visible-light excitation, their special geometry enables intramolecular charge transfer to induce a charge-transfer state, which was first demonstrated to accept electrons from electron donors. The resulting long-lived reduced photosensitizer was confirmed to trigger consecutive intermolecular electron transfers for boosting CO 2 -to-CO conversion. Remarkably, the Earth-abundant catalytic system with Z-6 and Fe-catalyst exhibits outstanding performance with a turnover number of >20 000 and 29.7% quantum yield, representing excellent catalytic performance among the molecular catalytic systems and highly superior to that of noble-metal photosensitizer Ir(ppy) 2 (bpy) + under similar conditions. Experimental and theoretical investigations comprehensively unveil the structure-activity relationship, opening up a new horizon for the development of Earth-abundant strong sensitizing chromophores for boosting artificial photosynthesis., (© The Author(s) 2024. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

The favorable benefit-risk profile of polatuzumab vedotin, as demonstrated in a pivotal Phase Ib/II randomized study (GO29365; NCT02257567), coupled with the need for effective therapies in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), prompted the need to accelerate polatuzumab vedotin development. An integrated, fit-for-purpose clinical pharmacology package was designed to support regulatory approval. To address key clinical pharmacology questions without dedicated clinical pharmacology studies, we leveraged non-clinical and clinical data for polatuzumab vedotin, published clinical data for brentuximab vedotin, a similar antibody-drug conjugate, and physiologically based pharmacokinetic and population pharmacokinetic modeling approaches. We review strategies and model-informed outcomes that contributed to regulatory approval of polatuzumab vedotin plus bendamustine and rituximab in R/R DLBCL. These strategies made polatuzumab vedotin available to patients earlier than previously possible; depending on the strength of available data and the regulatory/competitive environment, they may also prove useful in accelerating the development of other agents., Competing Interests: Declaration of Competing Interest Michael Z. Liao, Dan Lu, Tong Lu, Divya Samineni, Randall Dere, Andy Lin, Jamie Hirata, Ben-Quan Shen, Donglu Zhang, Dongwei Li, Chunze Li and Dale Miles were employees of Genentech, Inc. and held F. Hoffmann-La Roche Ltd. Stock/stock options at the time this work was performed. Leonid Gibiansky and Rong Deng are paid consultants for Genentech, Inc., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Detecting forged handwriting is important in a wide variety of machine learning applications, and it is challenging when the input images are degraded with noise and blur. This article presents a new model based on conformable moments (CMs) and deep ensemble neural networks (DENNs) for forged handwriting detection in noisy and blurry environments. Since CMs involve fractional calculus with the ability to model nonlinearities and geometrical moments as well as preserving spatial relationships between pixels, fine details in images are preserved. This motivates us to introduce a DENN classifier, which integrates stenographic kernels and spatial features to classify input images as normal (original, clean images), altered (handwriting changed through copy-paste and insertion operations), noisy (added noise to original image), blurred (added blur to original image), altered-noise (noise is added to the altered image), and altered-blurred (blur is added to the altered image). To evaluate our model, we use a newly introduced dataset, which comprises handwritten words altered at the character level, as well as several standard datasets, namely ACPR 2019, ICPR 2018-FDC, and the IMEI dataset. The first two of these datasets include handwriting samples that are altered at the character and word levels, and the third dataset comprises forged International Mobile Equipment Identity (IMEI) numbers. Experimental results demonstrate that the proposed method outperforms the existing methods in terms of classification rate.

Background: Vascular large conductance Ca 2+ -activated K + (BK) channel, composed of the α-subunit (BK-α) and the β1-subunit (BK-β1), is a key determinant of coronary vasorelaxation and its function is impaired in diabetic vessels. However, our knowledge of diabetic BK channel dysregulation is incomplete. The Sorbs2 (Sorbin homology [SoHo] and Src homology 3 [SH3] domains-containing protein 2), is ubiquitously expressed in arteries, but its role in vascular pathophysiology is unknown., Methods: The role of Sorbs2 in regulating vascular BK channel activity was determined using patch-clamp recordings, molecular biological techniques, and in silico analysis., Results: Sorbs2 is not only a cytoskeletal protein but also an RNA-binding protein that binds to BK channel proteins and BK-α mRNA, regulating BK channel expression and function in coronary smooth muscle cells. Molecular biological studies reveal that the SH3 domain of Sorbs2 is necessary for Sorbs2 interaction with BK-α subunits, while both the SH3 and SoHo domains of Sorbs2 interact with BK-β1 subunits. Deletion of the SH3 or SoHo domains abolishes the Sorbs2 effect on the BK-α/BK-β1 channel current density. Additionally, Sorbs2 is a target gene of the Nrf2 (nuclear factor erythroid-2-related factor 2), which binds to the promoter of Sorbs2 and regulates Sorbs2 expression in coronary smooth muscle cells. In vivo studies demonstrate that Sorbs2 knockout mice at 4 months of age display a significant decrease in BK channel expression and function, accompanied by impaired BK channel Ca 2+ -sensitivity and BK channel-mediated vasodilation in coronary arteries, without altering their body weights and blood glucose levels. Importantly, Sorbs2 expression is significantly downregulated in the coronary arteries of db/db type 2 diabetic mice., Conclusions: Sorbs2, a downstream target of Nrf2, plays an important role in regulating BK channel expression and function in vascular smooth muscle cells. Vascular Sorbs2 is downregulated in diabetes. Genetic knockout of Sorbs2 manifests coronary BK channelopathy and vasculopathy observed in diabetic mice, independent of obesity and glucotoxicity., Competing Interests: Disclosures None.

Owing to the electrical conductivity and periodic porosity, conductive metal-organic framework (cMOF) ultrathin films open new perspectives to photocatalysis. The space-selective assembly of catalytic sites and photosensitizers in/on cMOF is favorable for promoting the separation of photogenerated carriers and mass transfer. However, the controllable integration of functional units into the cMOF film is rarely reported. Herein, via the synergistic effect of steric hindrance and an electrostatic-driven strategy, the dinuclear-metal molecular catalysts (DMC) and perovskite (PVK) quantum dot photosensitizers were immobilized into channels and onto the surface of cMOF ultrathin films, respectively, affording [DMC@cMOF]-PVK film photocatalysts. In this unique heterostructure, cMOF not only facilitated the charge transfer from PVK to DMC but also guaranteed mass transfer. Using H 2 O as an electron donor, [DMC@cMOF]-PVK realized a 133.36 μmol·g -1 ·h -1 CO yield in photocatalytic CO 2 reduction, much higher than PVK and DMC-PVK. Owing to the excellent light transmission of films, multilayers of [DMC@cMOF]-PVK were integrated to increase the CO yield per unit area, and the 10-layer device realized a 1115.92 μmol·m -2 CO yield in 4 h, which was 8-fold higher than that of powder counterpart. This work not only lightens the development of cMOF-based composite films but also paves a novel avenue for an ultrathin film photocatalyst.

Infectious hematopoietic necrosis virus (IHNV) causes infectious hematopoietic necrosis and severe economic losses to salmon and trout aquaculture worldwide. Currently, the only commercial vaccine against IHNV is a DNA vaccine with some biosafety concerns. Hence, more effective vaccines and antiviral drugs are needed to prevent IHNV infection. In this study, 1,483 compounds were screened from a traditional Chinese medicine monomer library, and bufalin showed potential antiviral activity against IHNV. The 50% cytotoxic concentration of bufalin was >20 µM, and the 50% inhibitory concentration was 0.1223 µΜ against IHNV. Bufalin showed the inhibition of diverse IHNV strains in vitro , which confirmed that it had an inhibitory effect against all IHNV strains, rather than random activity against a single strain. The bufalin-mediated block of IHNV infection occurred at the viral attachment and RNA replication stages, but not internalization. Bufalin also inhibited IHNV infection in vivo and significantly increased the survival of rainbow trout compared with the mock drug-treated group, and this was confirmed by in vivo viral load monitoring. Our data showed that the anti-IHNV activity of bufalin was proportional to extracellular Na + concentration and inversely proportional to extracellular K + concentration, and bufalin may inhibit IHNV infection by targeting Na + /K + -ATPase. The in vitro and in vivo studies showed that bufalin significantly inhibited IHNV infection and may be a promising candidate drug against the disease in rainbow trout., Importance: Infectious hematopoietic necrosis virus (IHNV) is the pathogen of infectious hematopoietic necrosis (IHN) which outbreak often causes huge economic losses and hampers the healthy development of salmon and trout farming. Currently, there is only one approved DNA vaccine for IHN worldwide, but it faces some biosafety problems. Hence, more effective vaccines and antiviral drugs are needed to prevent IHNV infection. In this study, we report that bufalin, a traditional Chinese medicine, shows potential antiviral activity against IHNV both in vitro and in vivo . The bufalin-mediated block of IHNV infection occurred at the viral attachment and RNA replication stages, but not internalization, and bufalin inhibited IHNV infection by targeting Na + /K + -ATPase. The in vitro and in vivo studies showed that bufalin significantly inhibited IHNV infection and may be a promising candidate drug against the disease in rainbow trout., Competing Interests: The authors declare no conflict of interest.

Covalent organic frameworks (COFs) have been widely studied in photocatalytic CO 2 reduction reaction (CO 2 RR). However, pristine COFs usually exhibit low catalytic efficiency owing to the fast recombination of photogenerated electrons and holes. In this study, we fabricated a stable COF-based composite (GO-COF-366-Co) by covalently anchoring COF-366-Co on the surface of graphene oxide (GO) for the photocatalytic CO 2 reduction. Interestingly, in absolute acetonitrile (CH 3 CN), GO-COF-366-Co shows a high selectivity of 94.4 % for the photoreduction of CO 2 to formate, with a formate yield of 15.8 mmol/g, which is approximately four times higher than that using the pristine COF-366-Co. By contrast, in CH 3 CN/H 2 O (v : v=4 : 1), the main product for the photocatalytic CO 2 reduction over GO-COF-366-Co is CO (96.1 %), with a CO yield as high as 52.2 mmol/g, which is also approximately four times higher than that using the pristine COF-366-Co. Photoelectrochemical experiments demonstrate the covalent bonding of COF-366-Co and GO to form the GO-COF-366-Co composite facilitates charge separation and transfer significantly, thereby accounting for the enhanced catalytic activity. In addition, theoretical calculations and in situ Fourier transform infrared spectroscopy reveal H 2 O can stabilize the *COOH intermediate to further form a *CO intermediate via O-H(aq)⋅⋅⋅O(*COOH) hydrogen bonding, thus explaining the regulated photocatalytic performance., (© 2023 Wiley-VCH GmbH.)

Environmental regulations aim to reduce pollution and improve air quality and the health of residents. However, there is a lack of research focusing on the health and welfare effects of low-carbon city pilot policies. In this context, this study takes China's low-carbon city pilot policy as an entry point, focuses on the health effects of public environmental governance, and systematically investigates the effects and mechanisms of low-carbon city development on the health of middle-aged and elderly people by applying the difference-in-differences method. The study finds that low-carbon city (LCC) policy significantly improves the physical and mental health of middle-aged and elderly people, and the main transmission mechanism is the reduction in air pollution and improvement in social capital. These results hold following a series of robustness tests. Furthermore, low-carbon city construction can reduce hospitalization and outpatient costs for people over 45 years old by up to 3 % and 15.5 %, respectively. The findings of this study provide useful policy insights for ensuring sustainable improvement in environmental quality and public health., 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 Ltd.)

GPKPDviz is a Shiny application (app) dedicated to real-time simulation, visualization, and assessment of the pharmacokinetic/pharmacodynamic (PK/PD) models. Within the app, gPKPDviz is capable of generating virtual populations and complex dosing and sampling scenarios, which, together with the streamlined workflow, is designed to efficiently assess the impact of covariates and dosing regimens on PK/PD end points. The actual population data from clinical trials can be loaded into the app for simulation if desired. The app-generated dosing regimens include single or multiple dosing, and more complex regimens, such as loading doses or intermittent dosing. When necessary, the dosing regimens can be defined externally and loaded to the app for simulation. Using mrgsolve as the simulation engine, gPKPDviz is typically used for population simulation, however, with a slight modification of the mrgsolve model, gPKPDviz is capable of performing individual simulations with individual post hoc parameters, individual dosing logs, and individual sampling timepoints through an external dataset. A built-in text editor has a debugging feature for the mrgsolve model, providing the same error messages as model compilation in R. GPKPDviz has had stringent validation by comparing simulation results between the app and using mrgsolve in R. GPKPDviz is a member of the suite of Modeling and Simulation Shiny apps developed at Genentech to facilitate the typical modeling work in Clinical Pharmacology. For broader access to the Pharmacometric community, gPKPDviz has been published as an open-source application in GitHub under the terms of GNU General Public License., (© 2023 Genentech, Inc. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Controllable methanol production in artificial photosynthesis is highly desirable due to its high energy density and ease of storage. Herein, single atom Fe is implanted into TiO 2 /SrTiO 3 (TSr) nanotube arrays by two-step anodization and Sr-induced crystallization. The resulting Fe-TSr with both single Fe reduction centers and dominant oxidation facets (001) contributes to efficient CO 2 photoreduction and water oxidation for controlled production of CH 3 OH and CO/CH 4 . The methanol yield can reach to 154.20 µmol g cat -1 h -1 with 98.90% selectivity by immersing all the catalyst in pure water, and the yield of CO/CH 4 is 147.48 µmol g cat -1 h -1 with >99.99% selectivity when the catalyst completely outside water. This CH 3 OH yield is 50 and 3 times higher than that of TiO 2 and TSr and stands among all the state-of-the-art catalysts. The facile gas-solid and gas-liquid-solid phase switch can selectively control CH 3 OH production from ≈0% (above H 2 O) to 98.90% (in H 2 O) via slowly immersing the catalyst into water, where abundant •OH and H 2 O around Fe sites play important role in selective CH 3 OH production. This work highlights a new insight for water-mediated CO 2 photoreduction to controllably produce CH 3 OH., (© 2023 Wiley-VCH GmbH.)

Background: The concerted regulation of placenta microbiota and the immune responses secures the occurrence and development of pregnancy, while few studies reported this correlation. This study aimed to explore the relationship between the placenta microbiota and immune regulation during pregnancy., Methods: Twenty-six healthy pregnant women scheduled for elective cesarean section in the First Affiliated Hospital of Jinan University who met the inclusion criteria were recruited. Placenta and peripheral venous blood samples were collected. Microbiota in placental tissue was detected using high-throughput sequencing. Flow cytometry was used to detect immune cells in placental tissue and peripheral venous blood. ELISA and Luminex liquid chip technology were used to detect the content of cytokines in placental tissue and peripheral venous blood, respectively., Results: The placental microbiota has stimulating effects on the local immunity of the placenta and mainly stimulates the placental balance ratio CD56 + CD16 + /CD56 + CD16 and the placental macrophages, that is, it plays the role of immune protection and supporting nutrition. The stimulating effect of placental microbiota on maternal systemic immunity mainly induces peripheral Treg cells and B lymphocytes., Conclusion: The placental microbiota may be an important factor mediating local immune regulation in the placenta, and placental microbiota participates in the regulatory function of the maternal immune system., (© 2024. The Author(s).)

White matter hyperintensities, one of the major markers of cerebral small vessel disease, disrupt the integrity of neuronal networks and ultimately contribute to cognitive dysfunction. However, a deeper understanding of how white matter hyperintensities related to the connectivity patterns of brain hubs at the neural network level could provide valuable insights into the relationship between white matter hyperintensities and cognitive dysfunction. A total of 36 patients with moderate to severe white matter hyperintensities (Fazekas score ≥ 3) and 34 healthy controls underwent comprehensive neuropsychological assessments and resting-state functional MRI scans. The voxel-based graph-theory approach-functional connectivity strength was employed to systematically investigate the topological organization of the whole-brain networks. The white matter hyperintensities patients performed significantly worse than the healthy controls in episodic memory, executive function and information processing speed. Additionally, we found that white matter hyperintensities selectively affected highly connected hub regions, predominantly involving the medial and lateral prefrontal, precuneus, inferior parietal lobule, insula and thalamus. Intriguingly, this impairment was connectivity distance-dependent, with the most prominent disruptions observed in long-range connections (e.g. 100-150 mm). Finally, these disruptions of hub connectivity (e.g. the long-range functional connectivity strength in the left dorsolateral prefrontal cortex) positively correlated with the cognitive performance in white matter hyperintensities patients. Our findings emphasize that the disrupted hub connectivity patterns in white matter hyperintensities are dependent on connection distance, especially longer-distance connections, which in turn predispose white matter hyperintensities patients to worse cognitive function., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)