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Hong-Wu Wang,1,* Yi-Jin Hu,1,* Guo-Lin Wang2 1Department of Anesthesiology, TEDA International Cardiovascular Hospital of Tianjin Medical University, Tianjin, 300052, People’s Republic of China; 2Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin, 300074, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guo-Lin WangDepartment of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin, 300074, People’s Republic of ChinaTel/Fax +86 15822855566Email wanggl698521@163.comBackground: Protamine is a polycationic, and a strong basic peptide isolated from Clupeidae or Salmonidae fishes’ sperm, which is rich in arginine and highly alkaline.Objective: To explore the effect of lidocaine pre-treatment on protamine-induced pulmonary vascular reaction during the repair of congenital heart disease.Methods: Eighty patients undergoing repair of congenital heart disease were randomly divided into four groups: A1 (non-pulmonary hypertension + lidocaine pre-treatment) group, A2 (non-pulmonary hypertension + normal saline) group, B1 (pulmonary hypertension + lidocaine pre-treatment) group, and B2 (pulmonary hypertension + normal saline) group. Hemodynamic parameters, pulmonary inflammation, and pulmonary function were assessed at six intraoperative time points, two intraoperative time points and three intraoperative time points, respectively. P-value < 0.05 was considered statistically significant.Results: A2 group exhibited increased PAP, Paw, RI and A-aDO2. B2 group exhibited increased Paw, RI and A-aDO2 and decreased Cydn and OI after protamine administration. These changes were not observed in A1 and B1 group. Compared with A1 and B1 groups, plasma TXB2 level in A2 and B2 group was higher, but 6-keto-PGF1a in A2 and B2 groups was lower. Incidence of protamine adverse reactions in A1 and B1 group was lower than that in A2 and B2 group.Conclusion: Precondition of lidocaine before neutralization of heparin may be effective for protamine-induced pulmonary vascular reaction during CHD repair.Keywords: congenital heart disease, protamine, adverse reactions, extracorporeal circulation, pulmonary hypertension

Yuan Ding,1,* Wei Cui,2,* Dan Sun,1 Gui-Ling Wang,1 Yu Hei,1 Shuai Meng,1 Jian-Hua Chen,3 Ying Xie,1 Zhi-Qiang Wang4 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, 2School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing, 3School of Medicine, Jianghan University, Wuhan, People’s Republic of China; 4Department of Chemistry and Biochemistry, Kent State University Geauga, Burton, OH, USA *These authors contributed equally to this work Abstract: In vivo evaluation of drug delivery vectors is essential for clinical translation. In BALB/c nude mice bearing human breast cancer tumors, we investigated the biocompatibility, pharmacokinetics, and pharmacodynamics of doxorubicin (DOX)-loaded novel cell-penetrating peptide (CPP)-modified pH-sensitive liposomes (CPPL) (referred to as CPPL(DOX)) with an optimal CPP density of 4%. In CPPL, a polyethylene glycol (PEG) derivative formed by conjugating PEG with stearate via acid-degradable hydrazone bond (PEG2000-Hz-stearate) was inserted into the surface of liposomes, and CPP was directly attached to liposome surfaces via coupling with stearate to simultaneously achieve long circulation time in blood and improve the selectivity and efficacy of CPP for tumor targeting. Compared to PEGylated liposomes, CPPL enhanced DOX accumulation in tumors up to 1.9-fold (p

Shao-Hui Lin,1 Wei Cui,2 Gui-Ling Wang,1 Shuai Meng,1 Ying-Chun Liu,3 Hong-Wei Jin,4 Liang-Ren Zhang,4 Ying Xie1,4 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, 2School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing, 3Soft Matter Research Center, Department of Chemistry, Zhejiang University, Hangzhou, 4State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, People’s Republic of China Abstract: Albumin-based nanoparticles (NPs) are a promising technology for developing drug-carrier systems, with improved deposition and retention profiles in lungs. Improved understanding of these drug–carrier interactions could lead to better drug-delivery systems. The present study combines computational and experimental methods to gain insights into the mechanism of binding of albuterol sulfate (AS) to bovine serum albumin (BSA) on the molecular level. Molecular dynamics simulation and surface plasmon resonance spectroscopy were used to determine that there are two binding sites on BSA for AS: the first of which is a high-affinity site corresponding to AS1 and the second of which appears to represent the integrated functions of several low-affinity sites corresponding to AS2, AS3, and AS8. AS1 was the strongest binding site, established via electrostatic interaction with Glu243 and Asp255 residues in a hydrophobic pocket. Hydrogen bonds and salt bridges played a main role in the critical binding of AS1 to BSA, and water bridges served a supporting role. Based upon the interaction mechanism, BSA NPs loaded with AS were prepared, and their drug-loading efficiency, morphology, and -release profiles were evaluated. Successful clinical development of AS-BSA-NPs may improve therapy and prevention of bronchospasm in patients with reversible obstructive airway disease, and thus provide a solid basis for expanding the role of NPs in the design of new drug-delivery systems. Keywords: molecular dynamics, surface plasmon resonance, interaction mechanism, BSA nanoparticles, drug delivery systems

Yuan Ding,1,* Dan Sun,1,* Gui-Ling Wang,1 Hong-Ge Yang,1 Hai-Feng Xu,1 Jian-Hua Chen,2 Ying Xie,1,3 Zhi-Qiang Wang4 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, 2School of Medicine, Jianghan University, Wuhan, 3State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, People’s Republic of China; 4Department of Chemistry and Biochemistry, Kent State University Geauga, Burton, OH, USA *These authors contributed equally to this work Abstract: Cell-penetrating peptides (CPPs) as small molecular transporters with abilities of cell penetrating, internalization, and endosomal escape have potential prospect in drug delivery systems. However, a bottleneck hampering their application is the poor specificity for cells. By utilizing the function of hydration shell of polyethylene glycol (PEG) and acid sensitivity of hydrazone bond, we constructed a kind of CPP-modified pH-sensitive PEGylated liposomes (CPPL) to improve the selectivity of these peptides for tumor targeting. In CPPL, CPP was directly attached to liposome surfaces via coupling with stearate (STR) to avoid the hindrance of PEG as a linker on the penetrating efficiency of CPP. A PEG derivative by conjugating PEG with STR via acid-degradable hydrazone bond (PEG2000-Hz-STR, PHS) was synthesized. High-performance liquid chromatography and flow cytometry demonstrated that PHS was stable at normal neutral conditions and PEG could be completely cleaved from liposome surface to expose CPP under acidic environments in tumor. An optimal CPP density on liposomes was screened to guaranty a maximum targeting efficiency on tumor cells as well as not being captured by normal cells that consequently lead to a long circulation in blood. In vitro and in vivo studies indicated, in 4 mol% CPP of lipid modified system, that CPP exerted higher efficiency on internalizing the liposomes into targeted subcellular compartments while remaining inactive and free from opsonins at a maximum extent in systemic circulation. The 4% CPPL as a drug delivery system will have great potential in the clinical application of anticancer drugs in future. Keywords: long circulation, pharmacokinetics, lysosome escape, nanocarrier, pH-sensitive liposomes

Objective: To analyze the results of clinical and bacteriological examinations in patients with crush syndrome who suffered infectious complications after an earthquake in Sichuan, China.Methods: A total of 313 bacteriological samples among 147 patients with crush syndrome were collected. Infectious complications, results of microbiological examinations, potential risk factors of infection and mortality were analyzed statistically.Results: In the obtained database, 112 out of the 147 (75.7%) patients had infectious complications, in which, wound infection, pulmonary infection, and sepsis were most common. The time under the rubble and the time from injury to treatment were related to the occurrence of wound infection (P equal to 0.013, odds ratio 2.25; P equal to 0.017, odds ratio 2.31). Sepsis and wound infection were more common in patients who underwent fasciotomy or amputation than in those who did not (P equal to 0.001).Conclusion: Quick rescue and injury treatment can decrease the infection risk in crush syndrome patients. It is better to obtain microorganic proofs before applying antibiotics, and bacteriological and drug sensitivity data should be taken into account, especially considering that most of these infections are hospital-acquired and drug resistance. Emphasizing the accuracy and efficiency of wound management in emergency situations, cautiously assessing the indications for fasciotomy to avoid open wounds from unnecessary osteofascial compartment decompression incisions may decrease the incidence of infection and ameliorate the prognosis. [ABSTRACT FROM AUTHOR]

Objective: Subtrochanteric femoral fractures are severe injuries. Although many treatment methods have been developed, controversy exists regarding the optimal management of these fractures. This study evaluated the clinical outcome of subtrochanteric femoral fractures fixed with long proximal femoral nail antirotation (PFNA-long).Methods: Between October 2006 and February 2008, 25 patients with traumatic subtrochanteric fractures of the femur were treated with PFNA-long. Closed reduction and fixation were performed in 20 cases. In the remaining 5 cases, closed reduction was difficult, so limited open reduction was performed, with bone grafting in 4 cases and circumferential wiring in 4 cases.Results: The average follow-up time was 16.1 months. All subtrochanteric femoral fractures healed uneventfully except one case of delayed union. The mean union time was 26.2 weeks. Technical difficulties with nail insertion were encountered in 3 cases. No implant failure was observed.Conclusion: PFNA-long is effective in treatment of subtrochanteric femoral fractures, with a high rate of bone union, minor soft tissue damage, early return to functional exercise and few implant-related complications. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively analyze the medical treatment of 332 patients with lower leg fracture in Wenchuan earthquake admitted in West China Hospital.Methods: From May 12, 2008 to June 15, 2008, 332 patients with lower leg fracture injured in Wenchuan earthquake were treated in our hospital. The data on trauma condition and clinical treatment were collected and analyzed.Results: Among the 332 cases of lower leg fracture, there were 179 cases of open fracture, accounting for 53.9%, in which 91% belonged to Gustilo II or III injury with serious pollution. Many patients had posttraumatic complications, vascular and nerve injury, wound infection or osteofascial compartment syndrome. After medical treatment, blood vessels were reconnected, wound surface was repaired and wound infection was under control.Conclusion: For the patients with lower leg fracture in earthquake, we followed the principle of "complete debridement - restoring the continuity of bone bracket-timely recovering blood supply of limbs and repairing nerve damage - repair the wound surface at stage I or II " so as to reduce the incidence of amputation and infection. [ABSTRACT FROM AUTHOR]

Chronic diarrhea is a common bowel disorder; disturbance of intestinal microorganisms may play a role in its pathogenesis. This study assessed the clinical efficacy of lyophilized, heat-killed Lactobacillus acidophilus LB versus living lactobacilli in the treatment of chronic diarrhea. One hundred thirty-seven patients with chronic diarrhea were randomly allocated to receive either a 4-week course of 2 capsules of Lacteol Fort twice a day (Lacteol group, 69 patients) or a 4-week course of 5 chewable tablets of Lacidophilin three times a day (Lacidophilin group, 64 patients). The frequency of stools was recorded quantitatively, and semiquantitative parameters such as stool consistency, abdominal pain, distention, and feeling of incomplete evacuation were evaluated. At the second and fourth week of treatment, mean bowel frequency was significantly lower in the Lacteol group than in the Lacidophilin group (1.88 +/- 1.24 vs 2.64 +/- 1.12, 1.39 +/- 0.92 vs 2.19 +/- 1.05; P<.05). At the end of the treatment, the clinical symptoms were markedly improved in the Lacteol group, indicating that L. acidophilus LB is more effective than living lactobacilli in the treatment of chronic diarrhea. [ABSTRACT FROM AUTHOR]

Criteria of obesity in the Chinese population with multiple metabolic risk factors remains unclear. The objective was to determine the best anthropometrical measurements with regard to the metabolic syndrome (MetS) and to propose optimal cut-off values. Between April and August, 2007, 3,704 men and 6,392 women aged 18-85 years were recruited from four community centers. Medical examinations included measurement of weight, height, waist circumference (WC), hip circumference, fasting blood triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), glucose concentrations, and blood pressure (BP). Body mass index (BMI), waist to hip ratio (WHR), WC and waist to stature ratio (WSR) were calculated. Four metabolic risk factors were examined: 1) high BP; 2) high levels of TG; 3) low levels of HDL-C; 4) impaired glucose tolerance. The relationships between studied indices and risk factors were analyzed using partial correlation analyses, analysis of variance (ANOVA), linear regression, and Receiver Operator Characteristic (ROC) curve analysis. The optimal cut-off values of each obesity index were calculated using ROC analysis respectively. All obesity indices were positively associated with metabolic risk factors. Area under curve (AUC) of WC was the largest for >= 2 risk factors after adjustment for age in both genders. Optimal cut-off points for WC were 89 cm in men, and 80.5cm, 82.5cm, and 89.5cm in < 40-yr, 40-60-yr, and > 60-yr women respectively. Waist circumference is best associated with metabolic risk factors among the studied indices in Chinese adults. Indices of abdominal obesity for older age groups tend to be higher than younger age groups in women. [ABSTRACT FROM AUTHOR]

The ubiquitin-proteasome system (UPS) plays crucial roles in cellular processes including plant growth, development, and stress responses. In this study, we report that a pair of E3 ubiquitin ligases, AvrPiz-t-interaction protein 6 (APIP6) and IPA1-interaction protein 1 (IPI1), intricately target early flowering3 (ELF3) paralogous proteins to control rice immunity and flowering. APIP6 forms homo-oligomers or hetero-oligomers with IPI1. Both proteins interact with OsELF3-2, promoting its degradation to positively control resistance against the rice blast fungus (Magnaporthe oryzae). Intriguingly, overexpression of IPI1 in Nipponbare caused significantly late-flowering phenotypes similar to the oself3-1 mutant. Except for late flowering, oself3-1 enhances resistance against M. oryzae. IPI1 also interacts with and promotes the degradation of OsELF3-1, a paralog of OsELF3-2. Notably, IPI1 and APIP6 synergistically modulate OsELF3s degradation, finely tuning blast disease resistance by targeting OsELF3-2, while IPI1 controls both disease resistance and flowering by targeting OsELF3-1. This study unravels multiple functions for a pair of E3 ligases in rice., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: With the continued prevalence of COVID-19, repeated infection caused by SARS-CoV-2 has become common. However, studies on immune persistence post Omicron XBB reinfection are limited., Methods: We prospectively studied the durability and cross-reactivity of neutralizing antibodies (NAbs) and T cell responses among 20 subjects who suffered Omicron BA.5 infection with or without Omicron XBB reinfection over 6-month through the pseudovirus neutralization test and the fluorospot assay., Results: NAbs against EG.5.1, BA.2.86, and JN.1 subvariants were decreased and undetectable at 6-month post Omicron BA.5 infection, while those elicited by Omicron XBB reinfection were significant increased and remained detectable against all detected variants within 6-month. Furthermore, in subjects with Omicron XBB reinfection, memory T cell responses could cross-recognized wild-type and Omicron spike peptides and reached peak at 3-month. Interestingly, comparable robust T cell responses were observed among non-seroconverted subjects post Omicron XBB exposure., Conclusion: Though the NAbs against various emerging Omicron subvariants elicited by Omicron XBB reinfection can persist for at least 6-month, the HCWs should strengthen personal protection and timely be immunized with updated vaccines upon current circulating variants or conserved T epitope., 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 Zhao, Li, Zhang, Chen, Zhao, Wu, Wang, Xu, Lv, Jiang, Wang and Fang.)

Cell-penetrating peptides (CPPs) are short (typically 5-30 amino acids), cationic, amphipathic, or hydrophobic peptides that facilitate the cellular uptake of diverse cargo molecules by eukaryotic cells via direct translocation or endocytosis across the plasma membrane. CPPs can deliver a variety of bioactive cargos, including proteins, peptides, nucleic acids, and small molecules into the cell. Once inside, the delivered cargo may function in the cytosol, nucleus, or other subcellular compartments. Numerous CPPs have been used for studies and drug delivery in mammalian systems. Although CPPs have many potential uses in plant research and agriculture, the application of CPPs in plants remains limited. Here we review the structures and mechanisms of CPPs and highlight their potential applications for sustainable agriculture., Competing Interests: Declaration of interests The authors have no interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Halorhodospira (Hlr.) halochloris is a triply extremophilic phototrophic purple sulfur bacterium, as it is thermophilic, alkaliphilic, and extremely halophilic. The light-harvesting-reaction center (LH1-RC) core complex of this bacterium displays an LH1-Q y transition at 1,016 nm, which is the lowest-energy wavelength absorption among all known phototrophs. Here we report the cryo-EM structure of the LH1-RC at 2.42 Å resolution. The LH1 complex forms a tricyclic ring structure composed of 16 αβγ-polypeptides and one αβ-heterodimer around the RC. From the cryo-EM density map, two previously unrecognized integral membrane proteins, referred to as protein G and protein Q, were identified. Both of these proteins are single transmembrane-spanning helices located between the LH1 ring and the RC L-subunit and are absent from the LH1-RC complexes of all other purple bacteria of which the structures have been determined so far. Besides bacteriochlorophyll b molecules (B1020) located on the periplasmic side of the Hlr. halochloris membrane, there are also two arrays of bacteriochlorophyll b molecules (B800 and B820) located on the cytoplasmic side. Only a single copy of a carotenoid (lycopene) was resolved in the Hlr. halochloris LH1-α3β3 and this was positioned within the complex. The potential quinone channel should be the space between the LH1-α3β3 that accommodates the single lycopene but does not contain a γ-polypeptide, B800 and B820. Our results provide a structural explanation for the unusual Q y red shift and carotenoid absorption in the Hlr. halochloris spectrum and reveal new insights into photosynthetic mechanisms employed by a species that thrives under the harshest conditions of any phototrophic microorganism known., (© 2024 The Authors. Journal of Integrative Plant Biology published by John Wiley & Sons Australia, Ltd on behalf of Institute of Botany, Chinese Academy of Sciences.)

A great number of COVID-19 patients was caused by Omicron BA.5 subvariant between December 2022 and January 2023 after the end of the zero-COVID-19 policy in China. In this study, we clarified the epidemiological and immunological characteristics of 457 enrolled middle-aged and elderly population in two housing estates after Omicron BA.5 wave. A total of 89.9 % (411/457) individuals have suffered Omicron BA.5 infection, among which 78.1 % (321/411) were symptomatic. The elderly patients were more likely to show fatigue and had longer symptomatic period than that of middle-aged patients post Omicron BA.5 infection. Omicron XBB and BA.2.86 subvariants extensively escaped the immunity elicited by Omicron BA.5 infection. The level of neutralizing antibody was mostly affected by vaccination doses rather than underlying disease status in these participants. It is very important to strengthen the epidemiological investigation and immune resistance assessment among elderly population for control of emerging SARS-CoV-2 variants., 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.)

Background: Lung cancer (LC) combined with chronic obstructive pulmonary disease (COPD) is a common combination of comorbidities. Anti-inflammation and modulation of oxidative/antioxidative imbalance may prevent COPD-induced LC, and are also crucial to the treatment of LC combined with COPD. Modern studies have shown that Tao Hong Si Wu Tang (THSW) has vasodilatory, anti-inflammatory, anti-fatigue, anti-shock, immunoregulatory, lipid-reducing, micronutrient-supplementing, and anti-allergy effects., Aim: To observe the effects of THSW on COPD and LC in mice., Methods: A total of 100 specific pathogen-free C57/BL6 mice were randomly divided into five groups: Blank control group (group A), model control group (group B), THSW group (group C), IL-6 group (group D), and THSW + IL-6 group (group E), with 20 mice in each group. A COPD mouse model was established using fumigation plus lipopolysaccharide intra-airway drip, and an LC model was replicated by in situ inoculation using the Lewis cell method., Results: The blank control group exhibited a clear alveolar structure. The model control and IL-6 groups had thickened alveolar walls, with smaller alveolar lumens, interstitial edema, and several inflammatory infiltrating cells. Histopathological changes in the lungs of the THSW and THSW + IL-6 groups were less than those of the model control group. The serum IL-1β, IL-6, and TNF-α levels and IL-6R, JAK, p-JAK, STAT1/3, p-STAT1/3, FOXO, p-FOXO, and IL-7R expression levels in lung tissues of mice in the rest of the groups were significantly higher than those of the blank control group ( P < 0.01). Compared with the model control group, the IL-6 group demonstrated significantly higher levels for the abovementioned proteins in the serum and lung tissues ( P < 0.01), and the THSW group had significantly higher serum IL-1β, IL-6, and TNF-α levels and IL-7R expression levels in lung tissues ( P < 0.01) but significantly decreased IL-6R, JAK, p-JAK, STAT1/3, p-STAT1/3, FOXO, p-FOXO, and IL-7R levels ( P < 0.01)., Conclusion: THSW reduces the serum IL-1β, IL-6, and TNF-α levels in the mouse model with anti-inflammatory effects. Its anti-inflammatory mechanism lies in inhibiting the overactivation of the JAK/STAT1/3 signaling pathway., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: A mouse silicosis model was constructed by injecting silicon dioxide (SiO(2)) particles into the trachea to explore the effect and mechanism of Cordyceps cicadae polysaccharides (CCP) on ameliorating pulmonary fibrosis in silicosis mice. Methods: In May 2023, CCP were extracted and isolated, the monosaccharide composition and functional group composition were analyzed by high performance liquid chromatography and Fourier transform infrared spectroscopy. C57BL/6J mice were injected with 50 μl 50 mg/ml SiO(2) suspension to construct silicosis mouse model, which were then randomly divided into model group, CCP intervention groups [low dose group (LCCP group), medium dose group (MCCP group) and high dose group (HCCP group) ], the control group was administered by physiological saline, 8 mice in each group. Mice in the CCP intervention groups received oral gavage administration once daily with CCP solution (100, 200 and 400 mg/kg), while control group and model group received physiological saline, lasted for 30 days. The body weight of mice was recorded and the lung coefficient was calculated. The pathomorphological changes of mouse lung tissue were determined by HE and Masson staining. The contents of fibrosis indexes [hydroxyproline acid (HYP), connective tissue growth factor (CTGF) and matrix metallopeptidase 2 (MMP-2) ] of lung tissue and the pro-inflammatory factors[tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) ] of lung tissue and alveolar lavage fluid were determined by ELISA. The expression level of Collagen Ⅰ was determined by immunohistochemistry. The relative protein expression levels of transforming growth factor-β1 (TGF-β1), P-Smad2, α-smooth muscle actin (α-SMA), Toll-like receptor 4 (TLR4), nuclear factor kappa-B p65 (NF-κBp65) and myeloid differentiation primary response gene 88 (MyD88) in lung tissue were determined by Western blot. Results: The total sugar content of the CCP was 86.78%, composed of D-mannose, D-rhamnose, D-glucose and D-galactose, with a molar ratio of 12.71∶1.53∶1.00∶12.64. The infrared spectrum indicated the characteristic groups of its polysaccharides. Compared with the control group, the body weight of mice in the model group was decreased, lung coefficient was increased, the contents of HYP, CTGF and MMP-2 in lung tissue were increased, and the contents of TNF-α, IL-1β and IL-6 in lung tissue and alveolar lavage fluid were increased ( P <0.05). The mice lung showed massive inflammatory cell infiltration and collagen fiber deposition, and the silicosis fibrosis was severe. The expression of CollagenⅠin lung tissue of model group was increased, and the proteins expression levels of TGF-β1, P-Smad2/Smad2, α-SMA, TLR4, NF-κBp65 and MyD88 were increased in mouse lung tissue ( P <0.05). Compared with the model group, the body weights of mice in the MCCP and HCCP groups were increased, the lung coefficients were decreased, the contents of HYP, CTGF and MMP-2 in lung tissue were decreased, and the contents of TNF-α, IL-1β and IL-6 in lung tissue and alveolar lavage fluid were decreased ( P <0.05). The inflammatory cell infiltration in the lung was reduced, and the degree of fibrosis was improved to varying degrees. The expression level of CollagenⅠwas down-regulated in the lung tissue of MCCP and HCCP groups, and the protein expression levels of TGF-β1, P-Smad2/Smad2, α-SMA, TLR4, NF-κBp65 and MyD88 were decreased in lung tissue ( P <0.05) . Conclusion: The CCP could reduce the levels of fibrosis-related indicators and pro-inflammatory factors in lung tissue, ameliorating mouse lung inflammation and silicosis fibrosis caused by SiO(2) particles by inhibiting the activation of TGF-β1/Smad pathway and TLR4/nuclear factor kappa-B (NF-κB) pathway.

Carrot is a highly significant vegetable cultivated worldwide and possesses a unique aroma with abundant edible and medicinal values. However, it remains largely unknown whether jasmonic acid could regulate aroma formation in carrot. Here, an integrated analysis of the volatile metabolome and transcriptome of carrot roots exposed to different concentrations of methyl jasmonate (MeJA) was performed. The results revealed 1,227 volatile organic compounds and 972 differential accumulated metabolites, with terpenes representing the largest portion. MeJA treatment evidently increased the relative odor activity values as well as the accumulation of most volatile compounds. In addition, 4,787 differentially expressed genes were identified and subjected to function enrichment analysis, indicating a role of terpene biosynthesis and metabolism in response to MeJA application. A network consisting of 4,680 transcription factor-structural pairs that showed highly significant positive correlations was constructed, which may be utilized as genetic targets for examining terpene accumulation and aroma formation elicited by methyl jasmonate. The results from the present work substantially improved our understanding of MeJA-mediated aroma formation in carrot., 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, Wu, Chen, Xu, An, Ren and Xiong.)

Plant pathogens usually secrete effectors to suppress the host immune response, resulting in effector-triggered susceptibility (ETS). Plants use nucleotide-binding leucine-rich repeat receptors (NLRs) to detect specific effectors and elicit effector-triggered immunity (ETI). Two recent papers (Liu et al. and Zhang et al.) have made promising progress in controlling rice blast by modulating ETS and ETI., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Soil salinization leads to a reduction in arable land area, which seriously endangers food security. Developing saline-alkali land has become a key measure to address the contradiction between population growth and limited arable land. Rice is the most important global food crop, feeding half of the world's population and making it a suitable choice for planting on saline-alkali lands. The traditional salt-alkali improvement method has several drawbacks. Currently, non-thermal plasma (NTP) technology is being increasingly applied in agriculture. However, there are few reports on the cultivation of salt/alkali-tolerant rice. Under alkaline stress, argon NTP treatment significantly increased the germination rate of Longdao 5 (LD5) rice seeds. In addition, at 15 kV and 120 s, NTP treatment significantly increased the activity of antioxidant enzymes such as catalase and SOD. NTP treatment induced changes in genes related to salt-alkali stress in rice seedlings, such as chitinase and xylanase inhibitor proteins, which increased the tolerance of the seeds to salt-alkali stress. This experiment has expanded the application scope of NTP in agriculture, providing a more cost-effective, less harmful, and faster method for developing salt-alkali-tolerant rice and laying a theoretical foundation for cultivating NTP-enhanced salt-alkali-tolerant rice., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Adenosine deaminases acting on RNA 1(ADAR1), an RNA editing enzyme that converts adenosine to inosine by deamination in double-stranded RNAs, plays an important role in occurrence and progression of various types of cancer. Ferroptosis has emerged as a hot topic of cancer research in recent years. We have previously reported that ADAR1 promotes breast cancer progression by regulating miR-335-5p and METTL3. However, whether ADAR1 has effects on ferroptosis in breast cancer cells is largely unknown. In this study, we knocked down ADAR1 using CRISPR-Cas9 technology or over-expressed ADAR1 protein using plasmid expressing ADAR1 in MCF-7 and MDA-MB-231 breast cancer cell lines, then detected cell viability, and levels of ROS, MDA, GSH, Fe 2+ , GPX4 protein and miR-335-5p. We showed that the cell proliferation was inhibited, levels of ROS, MDA, Fe 2+ , and miR-335-5p were increased, while GSH and GPX4 levels were decreased after loss of ADAR1, compared to the control group. The opposite effects were observed after ADAR1 overexpression in the cells. Further, we demonstrated that ADAR1-controlled miR-335-5p targeted Sp1 transcription factor of GPX4, a known ferroptosis molecular marker, leading to inhibition of ferroptosis by ADAR1 in breast cancer cells. Moreover, RNA editing activity of ADAR1 is not essential for inducing ferroptosis. Collectively, loss of ADAR1 induces ferroptosis in breast cancer cells by regulating miR-335-5p/Sp1/GPX4 pathway. The findings may provide insights into the mechanism by which ADAR1 promotes breast cancer progression via inhibiting ferroptosis., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Insomnia disorder (ID) is one of the most common sleep problems, usually accompanied by anxiety and depression symptoms. Functional magnetic resonance imaging (fMRI) study suggests that both poor sleep quality and negative emotion are linked to the dysregulation of brain network related to emotion processing in ID patients. Acupuncture therapy has been proven effective in improving sleep quality and mood of ID patients, but the involved neurobiological mechanism remains unclear. We aimed to investigate the modulation effect of acupuncture on resting-state functional connectivity (rsFC) of the emotional network (EN) in patients experiencing insomnia., Methods: A total of 30 healthy controls (HCs) and 60 ID patients were enrolled in this study. Sixty ID patients were randomly assigned to real and sham acupuncture groups and attended resting-state fMRI scans before and after 4 weeks of acupuncture treatment. HCs completed an MRI/fMRI scan at baseline. The rsFC values within EN were calculated, and Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), Hyperarousal Scale (HAS), and actigraphy data were collected for clinical efficacy evaluation., Results: Resting-state FC analysis showed abnormalities in rsFC centered on the thalamus and dorsolateral prefrontal cortex within EN of ID patients compared to HCs. After real acupuncture treatment, rsFC of the anterior cingulate cortex, hippocampus, and amygdala were increased compared with the sham acupuncture group (p < 0.05, FDR corrected). In real acupuncture group, the rsFC value was decreased between left amygdala and left thalamus after 4 weeks of treatment compared with baseline. A trend of correlation was found that the increased rsFC value between the right amygdala and left hippocampus was positively correlated with the decreased HAMA scores across all ID patients, and the decreased left amygdala rsFC value with the left thalamus was negatively correlated with the increased sleep efficiency in the real acupuncture group., Conclusion: Our findings showed that real acupuncture could produce a positive effect on modulating rsFC within network related to emotion processing in ID patients, which may illustrate the central mechanism underlying acupuncture for insomnia in improving sleep quality and emotion regulation., Trial Registration: http://www.chictr.org.cn ., ChiCTR1800015282, 20/03/2018., (© 2024. The Author(s).)

Hepatocyte growth factor (HGF) and its receptor, c-Met, play important roles in the occurrence, development, and treatment of gastric cancer (GC). This review explored the function of the HGF/c-Met signaling pathway in GC and its potential targeted therapeutic mechanisms. As one of the most common malignant tumors worldwide, GC has a complex pathogenesis and limited therapeutic options. Therefore, a thorough understanding of the molecular mechanism of GC is very important for the development of new therapeutic methods. The HGF/c-Met signaling pathway plays an important role in the proliferation, migration, and invasion of GC cells and has become a new therapeutic target. This review summarizes the current research progress on the role of HGF/c-Met in GC and discusses targeted therapeutic strategies targeting this signaling pathway, providing new ideas and directions for the treatment of GC., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants raises concerns regarding the effectiveness of immunity acquired from previous Omicron subvariants breakthrough infections (BTIs) or reinfections (RIs) against the current circulating Omicron subvariants. In this study, we prospectively investigate the dynamic changes of virus-specific antibody and T cell responses among 77 adolescents following Omicron BA.2.3 BTI with or without subsequent Omicron BA.5 RI. Notably, the neutralizing antibodies (NAbs) titers against various detected SARS-CoV-2 variants, especially the emerging Omicron CH.1.1, XBB.1.5, XBB.1.16, EG.5.1, and JN.1 subvariants, exhibited a significant decrease along the time. A lower level of IgG and NAbs titers post-BTI was found to be closely associated with subsequent RI. Elevated NAbs levels and shortened antigenic distances were observed following Omicron BA.5 RI. Robust T cell responses against both Omicron BA.2- and CH.1.1-spike peptides were observed at each point visited. The exposure to Omicron BA.5 promoted phenotypic differentiation of virus-specific memory T cells, even among the non-seroconversion adolescents. Therefore, updated vaccines are needed to provide effective protection against newly emerging SARS-CoV-2 variants among adolescents., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Purple phototrophic bacteria possess light-harvesting 1 and reaction center (LH1-RC) core complexes that play a key role in converting solar energy to chemical energy. High-resolution structures of LH1-RC and RC complexes have been intensively studied and have yielded critical insight into the architecture and interactions of their proteins, pigments, and cofactors. Nevertheless, a detailed picture of the structure and assembly of LH1-only complexes is lacking due to the intimate association between LH1 and the RC. To study the intrinsic properties and structure of an LH1-only complex, a genetic system was constructed to express the Thermochromatium (Tch.) tepidum LH1 complex heterologously in a modified Rhodospirillum rubrum mutant strain. The heterologously expressed Tch. tepidum LH1 complex was isolated in a pure form free of the RC and exhibited the characteristic absorption properties of Tch. tepidum. Cryo-EM structures of the LH1-only complexes revealed a closed circular ring consisting of either 14 or 15 αβ-subunits, making it the smallest completely closed LH1 complex discovered thus far. Surprisingly, the Tch. tepidum LH1-only complex displayed even higher thermostability than that of the native LH1-RC complex. These results reveal previously unsuspected plasticity of the LH1 complex, provide new insights into the structure and assembly of the LH1-RC complex, and show how molecular genetics can be exploited to study membrane proteins from phototrophic organisms whose genetic manipulation is not yet possible., 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.)

Background: The morphology of tumor thrombus varies from person to person and it may affect surgical methods and tumor prognosis. However, studies on the morphology of tumor thrombus are limited. The purpose of our study was to evaluate the impact of tumor thrombus morphology on surgical complexity., Methods: We retrospectively reviewed the clinical data of 229 patients with renal cell carcinoma combined with inferior vena cava (IVC) tumor thrombus who underwent surgical treatment at Peking University Third Hospital between January 2014 and December 2021. The patients were divided into floating morphology (107 patients) and filled morphology (122 patients) tumor thrombi groups. Chi-square and Mann-Whitney U tests were used for categorical and continuous variables, respectively. Postoperative complications were evaluated using the Clavien-Dindo surgical complication classification method., Results: Patients with filled morphology tumor thrombus required more surgical techniques than those with floating morphology tumor thrombus, which was reflected in more open surgeries (P < 0.001), more IVC interruptions (P <0.001), lesser use of the delayed occlusion of the proximal inferior vena cava (DOPI) technique (P < 0.001), and a greater need for cut-off of the short hepatic vein (P < 0.001) and liver dissociation (P = 0.001). Filled morphology significantly increased the difficulty of surgery in patients with renal cell carcinoma with tumor thrombus, reflected in longer operation time (P < 0.001), more surgical blood loss (P <0.001), more intra-operative blood transfusion (P < 0.001), and longer postoperative hospital stay (P < 0.001). Filled morphology tumor thrombus also led to more postoperative complications (53% vs. 20%; P < 0.001)., Conclusion: Compared with floating morphology thrombus, filled morphology thrombus significantly increased the difficulty of surgery in patients with renal cell carcinoma with IVC tumor thrombus., (© 2024. The Author(s).)

Wang et al reported 1063 cases from the initial 14 d of intensive care unit (ICU) stay, and analyzed relevant data such as age, comorbidities, recent dosages, vapor pressure dosages, duration of mechanical ventilation, length of ICU stay, and rehabilitation therapy, which are closely related to ICU-acquired weakness (ICU-AW). It is suggested that the length of ICU stay and the duration of mechanical ventilation are the main factors. ICU-AW is the most common neuromuscular injury in the ICU, which affects clinical progression and outcomes of patients. This manuscript helps to improve the early recognition of ICU-AW, thereby reducing mortality and improving prognosis., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Plants typically activate distinct defense pathways against various pathogens. Heightened resistance to one pathogen often coincides with increased susceptibility to another pathogen. However, the underlying molecular basis of this antagonistic response remains unclear. Here, we demonstrate that mutants defective in the transcription factor ETHYLENE-INSENSITIVE 3-LIKE 2 (OsEIL2) exhibited enhanced resistance to the biotrophic bacterial pathogen Xanthomonas oryzae pv oryzae and to the hemibiotrophic fungal pathogen Magnaporthe oryzae, but enhanced susceptibility to the necrotrophic fungal pathogen Rhizoctonia solani. Furthermore, necrotroph-induced OsEIL2 binds to the promoter of OsWRKY67 with high affinity, leading to the upregulation of salicylic acid (SA)/jasmonic acid (JA) pathway genes and increased SA/JA levels, ultimately resulting in enhanced resistance. However, biotroph- and hemibiotroph-induced OsEIL2 targets OsERF083, resulting in the inhibition of SA/JA pathway genes and decreased SA/JA levels, ultimately leading to reduced resistance. Our findings unveil a previously uncharacterized defense mechanism wherein two distinct transcriptional regulatory modules differentially mediate immunity against pathogens with different lifestyles through the transcriptional reprogramming of phytohormone pathway genes., (© 2024 The Authors. New Phytologist © 2024 New Phytologist Foundation.)

Although the antagonistic effects of host resistance against biotrophic and necrotrophic pathogens have been documented in various plants, the underlying mechanisms are unknown. Here, we investigated the antagonistic resistance mediated by the transcription factor ETHYLENE-INSENSITIVE3-LIKE 3 (OsEIL3) in rice. The Oseil3 mutant confers enhanced resistance to the necrotroph Rhizoctonia solani but greater susceptibility to the hemibiotroph Magnaporthe oryzae and biotroph Xanthomonas oryzae pv. oryzae. OsEIL3 directly activates OsERF040 transcription while repressing OsWRKY28 transcription. The infection of R. solani and M. oryzae or Xoo influences the extent of binding of OsEIL3 to OsWRKY28 and OsERF040 promoters, resulting in the repression or activation of both salicylic acid (SA)- and jasmonic acid (JA)-dependent pathways and enhanced susceptibility or resistance, respectively. These results demonstrate that the distinct effects of plant immunity to different pathogen types are determined by two transcription factor modules that control transcriptional reprogramming and the SA and JA pathways., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Due to mechanical imbalance in the spine, elderly scoliosis patients tend to develop vertebral fracture nonunion, i.e. , Kümmell disease, when osteoporotic vertebral compression fractures occur. However, accompanying vertebral rotational deformities make surgical procedures challenging risky. Such patients are usually compelled to undergo conservative treatment and there are very few reports on minimally invasive surgeries for them. We first-time report a patient with Kümmell disease and lumbar scoliosis treated with percutaneous kyphoplasty (PKP) under O-arm guidance., Case Summary: An 89-year-old female was admitted to the hospital due to delayed low back pain after a fall. She was diagnosed with Kümmell disease based on physical and radiologic examinations. The patient experienced severe scoliosis and subsequently underwent O-arm-guided kyphoplasty, resulting in a significant alleviation of low back pain., Conclusion: PKP has good efficacy in treating Kümmell disease. However, surgical risks are elevated in scoliosis patients with Kümmell disease due to the abnormal anatomical structure of the spine. O-arm assisted operations play a crucial role in decreasing surgical risks., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvβ3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE's influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvβ3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvβ3. Activation of the integrin αvβ3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions.

The emergence of novel Omicron subvariants has raised concerns regarding the efficacy of immunity induced by prior Omicron subvariants breakthrough infection (BTI) or reinfection against current circulating Omicron subvariants. Here, we prospectively investigated the durability of antibody and T cell responses in individuals post Omicron BA.2.2 BTI, with or without subsequent Omicron BA.5 reinfection. Our findings reveal that the emerging Omicron subvariants, including CH.1.1, XBB, and JN.1, exhibit extensive immune evasion induced by previous infections. Notably, the level of IgG and neutralizing antibodies were found to correlate with subsequent Omicron BA.5 reinfection. Fortunately, T cell responses recognizing both Omicron BA.2 and CH.1.1 peptides were observed. Furthermore, Omicron BA.5 reinfection may alleviate immune imprinting induced by WT-vaccination, bolster virus-specific ICS + T cell responses, and promote the phenotypic differentiation of virus-specific memory CD8 + T cells. Antigen-updated or T cell-conserved vaccines are needed to control the transmission of diverse emerging SARS-CoV-2 variants., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

F-box protein is a subunit of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex, which plays a critical role in regulating different pathways in plant immunity. In this study, we identified the rice (Oryza sativa) F-box protein OsFBX156, which targets the heat shock protein 70 (OsHSP71.1) to regulate resistance to the rice blast fungus Magnaporthe oryzae. Overexpression of OsFBX156 or knockout of OsHSP71.1 in rice resulted in the elevation of pathogenesis-related (PR) genes and an induction burst of reactive oxygen species (ROS) after flg22 and chitin treatments, thereby enhancing resistance to M. oryzae. Furthermore, OsFBX156 can promote the degradation of OsHSP71.1 through the 26S proteasome pathway. This study sheds lights on a novel mechanism wherein the F-box protein OsFBX156 targets OsHSP71.1 for degradation to promote ROS production and PR gene expression, thereby positively regulating rice innate immunity., (© 2024 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Conservation tillage (CT) is an important agronomic measure that facilitates soil organic carbon (SOC) accumulation by reducing soil disturbance and plant residue mulching, thus increasing crop yields, improving soil fertility and achieving C neutrality. However, our understanding of the microbial mechanism underlying SOC fraction accumulation under different tillage practices is still lacking. Here, a 6-year in situ field experiment was carried out to explore the effects of CT and traditional tillage (CK) practices on SOC fractions in an eolian sandy soil. Compared with CK, CT increased the particulate OC (POC) content in the 0-30 cm soil layer and the mineral-associated OC (MAOC) content in the 0-20 cm soil layer. Moreover, tillage type and soil depth had significant influences on the bacterial, fungal and protistan community compositions and structures. The co-occurrence network was divided into 4 ecological modules, and module 1 exhibited significant correlations with the POC and MOC contents. After determining their topological roles, we identified the keystone taxa in the network. The results indicated that the most common bacterial taxa may result in SOC loss due to low C use efficiency, while specific fungal (Cephalotrichum) and protistan (Cercozoa) species could facilitate SOC fraction accumulation by promoting macroaggregate formation and predation. Therefore, the increase in keystone fungi and protists, as well as the reduction in bacteria, drove module 1 community function, which in turn promoted SOC sequestration under CT. These results strengthen our understanding of microbial functions in the accrual of SOC fractions, which contributes to the development of conservation agriculture on the Northeast China Plain., 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 Li, Wang, Qiu, Yu, Liu, Wang and Duan.)

We report an experimental study of quantum point contacts defined in a high-quality strained germanium quantum well with layered electric gates. At a zero magnetic field, we observed quantized conductance plateaus in units of 2 e 2 / h . Bias-spectroscopy measurements reveal that the energy spacing between successive one-dimensional subbands ranges from 1.5 to 5 meV as a consequence of the small effective mass of the holes and the narrow gate constrictions. At finite magnetic fields perpendicular to the device plane, the edges of the conductance plateaus get split due to the Zeeman effect and Landé g factors were estimated to be ∼6.6 for the holes in the germanium quantum well. We demonstrate that all quantum point contacts in the same device have comparable performances, indicating a reliable and reproducible device fabrication process. Thus, our work lays a foundation for investigating multiple forefronts of physics in germanium-based quantum devices that require quantum point contacts as building blocks.

Purpose: We carried out the study aiming to explore and analyze the risk factors, the distribution of pathogenic bacteria, and their antibiotic-resistance characteristics influencing the occurrence of surgical site infection (SSI), to provide valuable assistance for reducing the incidence of SSI after traumatic fracture surgery., Methods: A retrospective case-control study enrolling 3978 participants from January 2015 to December 2019 receiving surgical treatment for traumatic fractures was conducted at Tangdu Hospital of Air Force Medical University. Baseline data, demographic characteristics, lifestyles, variables related to surgical treatment, and pathogen culture were harvested and analyzed. Univariate analyses and multivariate logistic regression analyses were used to reveal the independent risk factors of SSI. A bacterial distribution histogram and drug-sensitive heat map were drawn to describe the pathogenic characteristics., Results: Included 3978 patients 138 of them developed SSI with an incidence rate of 3.47% postoperatively. By logistic regression analysis, we found that variables such as gender (males) (odds ratio (OR) = 2.012, 95% confidence interval (CI): 1.235 - 3.278, p = 0.005), diabetes mellitus (OR = 5.848, 95% CI: 3.513 - 9.736, p < 0.001), hypoproteinemia (OR = 3.400, 95% CI: 1.280 - 9.031, p = 0.014), underlying disease (OR = 5.398, 95% CI: 2.343 - 12.438, p < 0.001), hormonotherapy (OR = 11.718, 95% CI: 6.269 - 21.903, p < 0.001), open fracture (OR = 29.377, 95% CI: 9.944 - 86.784, p < 0.001), and intraoperative transfusion (OR = 2.664, 95% CI: 1.572 - 4.515, p < 0.001) were independent risk factors for SSI, while, aged over 59 years (OR = 0.132, 95% CI: 0.059 - 0.296, p < 0.001), prophylactic antibiotics use (OR = 0.082, 95% CI: 0.042 - 0.164, p < 0.001) and vacuum sealing drainage use (OR = 0.036, 95% CI: 0.010 - 0.129, p < 0.001) were protective factors. Pathogens results showed that 301 strains of 38 species of bacteria were harvested, among which 178 (59.1%) strains were Gram-positive bacteria, and 123 (40.9%) strains were Gram-negative bacteria. Staphylococcus aureus (108, 60.7%) and Enterobacter cloacae (38, 30.9%) accounted for the largest proportion. The susceptibility of Gram-positive bacteria to Vancomycin and Linezolid was almost 100%. The susceptibility of Gram-negative bacteria to Imipenem, Amikacin, and Meropenem exceeded 73%., Conclusion: Orthopedic surgeons need to develop appropriate surgical plans based on the risk factors and protective factors associated with postoperative SSI to reduce its occurrence. Meanwhile, it is recommended to strengthen blood glucose control in the early stage of admission and for surgeons to be cautious and scientific when choosing antibiotic therapy in clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Production and hosting by Elsevier B.V.)

It is known that the oocyte has a limited capacity to acquire and metabolize glucose, and it must rely on cumulus cells (CCs) to take up glucose and produce pyruvate for use to produce ATP through oxidative phosphorylation. We therefore propose that miRNAs might regulate glucose metabolism (GM) in CCs and might be used as markers for oocyte quality assessment. Here, mouse CC models with impaired glycolysis or pentose phosphate pathway (PPP) were established, and miRNAs targeting the key enzymes in glycolysis/PPP were predicted using the miRNA target prediction databases. Expression of the predicted miRNAs was compared between CCs with normal and impaired glycolysis/PPP to identify candidate miRNAs. Function of the candidate miRNAs was validated by transfecting CCs or cumulus-oocyte-complexes (COCs) with miRNA inhibitors and observing effects on glucose metabolites of CCs and on competence of oocytes. The results validated that miR-23b-3p, let-7b-5p, 34b-5p and 145a-5p inhibited glycolysis, and miR-24-3p, 3078-3p,183-5p and 7001-5p inhibited PPP of CCs. Our observation using a more physiologically relevant model (intact cultured COCs) further validated the four glycolysis-targeting miRNAs we identified. Furthermore, miR-let-7b-5p, 34b-5p and 145a-5p may also inhibit PPP, as they decreased the production of glucose-6-phosphate. In conclusion, miRNAs play critical roles in GM of CCs and may be used as markers for oocyte quality assessment. Summary sentence:  We identified and validated eight new miRNAs that inhibit glycolysis and/or pentose phosphate pathways in cumulus cells (CCs) suggesting that miRNAs play critical roles in glucose metabolism of CCs and may be used for oocyte quality markers., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)