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Jian Yang,&ast; Chuan Wang Li,&ast; Jing Ru Zhang, Honglin Qiu, Xiu Li Guo, Wei Wang Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, 364000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Wang; Xiu Li Guo, Department of Endocrinology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, 364000, People’s Republic of China, Email 591187650@qq.com; 1256339602@qq.comObjective: Recent advances in perirenal adipose tissue (PAT) highlighted that PAT might involve in the pathogenesis of chronic inflammatory and dysfunctional metabolic diseases. This study assessed the association between perirenal fat thickness (PrFT) and metabolic dysfunction-associated fatty liver disease (MALFD) in type 2 diabetes mellitus (T2DM).Methods: This study comprised 867 eligible participants with T2DM. Trained reviewers collected anthropometric and biochemical measurements. The diagnosis of MAFLD was based on the latest international expert consensus statement. PrFT and fatty liver were evaluated by computed tomography. The visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by bioelectrical impedance analysis. The non-alcoholic fatty liver disease fibrosis score (NFS) and fibrosis-4 (FIB-4) index were used to assess progressive liver fibrosis in MAFLD.Results: Overall, the prevalence of MAFLD was 62.3% in T2DM. The PrFT in the MAFLD group was statistically increased than in the non-MAFLD group (P < 0.05). Correlation analysis showed that PrFT was significantly correlated with dysfunctional metabolic factors like body mass index, waist circumference, triglycerides, high-density lipoprotein cholesterol, systolic blood pressure, diastolic blood pressure, uric acid, and insulin resistance. Multiple regression analysis revealed that PrFT was positively correlated with NFS (β=0.146, P< 0.001) and FIB-4 (β=0.082, P=0.025) in the MAFLD. In contrast, PrFT was negatively correlated with CTL-S (β=− 0.188, P< 0.001). Furthermore, PrFT was also significantly associated with MAFLD independent of VFA and SFA, the OR (95% CI) was 1.279 (1.191– 1.374). Meanwhile, PrFT also had a good identifying value for MAFLD as VFA. The area under the curve (95% CI) value of PrFT identifying MAFLD was 0.782 (0.751– 0.812). The optimal cut-off value of PrFT was 12.6mm, with a sensitivity of 77.8% and specificity of 70.8%.Conclusion: PrFT was independently associated with MAFLD, NFS, and FIB-4 and showed a similar identifying value for MAFLD as VFA, which suggested that PrFT can be used as an alternative index to VFA.Keywords: metabolic dysfunction-associated fatty liver disease, liver fibrosis, perirenal fat thickness, obesity, type 2 diabetes mellitus

Yi-Lun Ge,1,&ast; Si-Yi Gong,1,&ast; Pu-Zhi Wang,1 Jia-Hui Yan,1 Wen Li,1 Jin-Ru Zhang,1 Hong Jin,1 Sheng Zhuang,1 Lei Hu,2 Chang-Wei Ding,2 Ya-Ping Yang,1 Fen Wang,3 Dan Li,4 Jing Chen,1 Cheng-Jie Mao,1,4 Ying-Chun Zhang,2 Kai Li,1 Chun-Feng Liu1,3,4 1Department of Neurology, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Ultrasound, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 3Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, People’s Republic of China; 4Department of Neurology, Suqian First Hospital, Suqian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Li, Department of Neurology, the Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Suzhou, Jiangsu, 215004, People’s Republic of China, Tel +86-512-6778-4179, Fax +86-512-6828-4303, Email liskai@126.comPurpose: Cognitive impairment (CI) is a common but debilitating non-motor symptom in Parkinson’s disease (PD). Although cerebrovascular functions are related to cognitive performance in healthy individuals, such a relation in PD remains elusive. This study aims to assess the association between cerebrovascular function and cognitive performance in PD individuals.Patients and Methods: Two-hundred-and-one PD individuals were retrospectively included. They were subsequently divided into two groups: PD with normal cognition (PD-NC) and PD with CI (PD-CI). Cerebral hemodynamic characteristics of the middle cerebral arteries were assessed by transcranial ultrasound. The association between scores in each cognitive domain and cerebral hemodynamic parameters was further analyzed using regression analyses. Additionally, a binary logistic regression model with backward stepwise procedure was applied to build the model for discriminating CI in PD individuals. An independent dataset of additional 46 PD individuals was used further.Results: The PD-CI group showed a relatively lower end-diastolic blood flow velocity (EDV, p < 0.05) and a higher resistive index (RI, p < 0.05) compared to the PD-NC group. RI showed significant associations with the memory item score of Montreal Cognitive Assessment (p < 0.05). A model combining clinical and hemodynamic variables was established with optimal efficiency (area under the curve, AUC = 0.651). Further replication of the model in an independent dataset yielded a great consistency (AUC = 0.704).Conclusion: In our study, cerebrovascular functions were significantly associated with the cognitive performance in PD individuals, especially with the memory task. The established model was effective in identifying CI in PD individuals, which might be a potentially useful tool to screen the cognitive decline in PD individuals at an early stage of the disease. Further studies with larger sample sizes in different populations are warranted.Keywords: Parkinson’s disease, cognitive impairment, transcranial ultrasound, resistive index

Wen-Yu Liu,1,&ast; Yu-Ting Zhu,2,&ast; Xian-Ming Xu,1 Jia-Rong Zhang,3 Xu-Pei Gan,1 De-Cui Cheng,1 Feng Lu,4 Cong Lu1 1Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, People’s Republic of China; 2Department of Gynecology Maternal and Child Health Hospital of Jiading District, Shanghai, 201800, People’s Republic of China; 3Department of Obstetrics and Gynecology, Zhongshan Hospital, Fudan University, Shanghai, 200030, People’s Republic of China; 4Department of Obstetrics and Gynecology, Songjiang Maternal and Child Health-Care Hospital, Shanghai, 201600, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cong Lu, Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 650 of Xinsongjiang Road, Songjiang District, Shanghai, 201600, People’s Republic of China, Tel +86-021-37798537, Email lucongtr5@163.com Feng Lu, Department of Obstetrics and Gynecology, Songjiang Maternal and Child Health-Care Hospital, No. 1010 of Xilin North Road, Songjiang District, Shanghai, 201600, People’s Republic of China, Tel +86-18918282005, Email rlufengni@163.comObjective: The present study aims to evaluate the relationship of thyroid function during the first trimester of pregnancy with lipid levels and pregnancy outcomes.Methods: Women who delivered babies at the Shanghai General Hospital between March 2019 and December 2019 with a known pregnancy outcome and complete data were included in the present study (n = 1779). A retrospective cohort study of all subjects with available first-trimester thyroid function testing and lipid levels data was conducted, and the relationship of thyroid function with lipid levels and pregnancy outcomes was evaluated. The data were analyzed using the SPSS software for statistical correlation.Results: The proportion of caesarean sections was higher in women with hypothyroxinemia (HIA) and hypothyroidism than in women with euthyroidism. Hypothyroidism was shown to be related with polyhydramnios, preterm labor and hypertriglyceridemia. HIA was correlated with increased rates of gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension and hypertriglyceridemia. Compared with the euthyroidism group, the hypothyroidism group had a higher apolipoprotein A1 (Apo A1) level and apolipoprotein B level; the subclinical hypothyroidism group had a higher total cholesterol (TC) level and low-density lipoprotein cholesterol level; the HIA group had higher triglyceride, high-density lipoprotein cholesterol levels and lower TC, Apo A1 levels. TC levels were positively correlated with the thyroid-stimulating hormone level and negatively correlated with free thyroxine (FT4) level, and free triiodothyronine and FT4 levels were positively correlated with GDM occurrence.Conclusion: Thyroid function in early pregnancy is associated with dyslipidemia and pregnancy outcomes; conventional screening of thyroid diseases in early pregnancy may help improve lipid levels and decrease adverse pregnancy outcomes.Keywords: first trimester, thyroid function tests, adverse pregnancy outcome, dyslipidemia

Qinchang Chen,1,* Kai Huang,2,* Lingling Li,2 Xixia Lin,2 Cong Ding,2 Junrui Zhang,3 Qingui Chen1 1Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 2Division of Vascular and Thyroid Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; 3Guangzhou Institute of Standardization, Guangzhou, China *These authors contributed equally to this work Purpose: We aimed to evaluate the association of serum uric acid on admission with long-term outcome of critically ill patients. Materials and methods: We conducted a retrospective cohort study using data extracted from the Medical Information Mart for Intensive Care III database. The primary endpoint was 90-day mortality. Propensity score matching (PSM) was performed, and multivariate Cox regression analysis was used to adjust for potential confounders. Receiver operating characteristic (ROC) curves were also used to assess the mortality predictions. Results: A total of 2,123 patients were included finally with a PSM cohort consisting of 556 90-day non-survivors matched 1:1 with 556 90-day survivors. No statistically significant difference of median admission uric acid was observed between the two groups (survivors 5.50 mg/dL vs non-survivors 5.60 mg/dL, p=0.536). ROC area under the curve was 0.511 (95% confidence interval [CI] 0.477–0.545), suggesting that uric acid had poor discriminative powers for predicting 90-day mortality. No significant association between uric acid and 90-day mortality was found (hazard ratio 1.00, 95% CI 0.98–1.03, p=0.6835). Conclusion: Serum uric acid on intensive care unit admission failed to predict 90-day mortality of critically ill patients. Keywords: uric acid, critical care, mortality, risk factors

Jiapeng Li,1,2 Yang Liu,2 Jingru Zhang,1,2 Xiaotong Yu,1,2 Xiaoling Wang,1 Libo Zhao11Department of Pharmacy, Beijing Children’s Hospital, Capital Medical University, 2Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China Background: The intestinal cytochrome P450 3A (CYP 3A) and P-glycoprotein (P-gp) present a barrier to the oral absorption of saquinavir (SQV). Resveratrol (RESV) has been indicated to have modulatory effects on P-gp and CYP 3A. Therefore, this study was to investigate the effects of RESV on P-gp and CYP 3A activities in vitro and in vivo on oral SQV pharmacokinetics in rats.Methods: In vitro, intestinal microsomes were used to evaluate RESV effect on CYP 3A-mediated metabolism of SQV; MDR1-expressing Madin–Darby canine kidney (MDCKII-MDR1) cells were employed to assess the impact of RESV on P-gp-mediated efflux of SQV. In vivo effects were studied using 10 rats randomly assigned to receive oral SQV (30 mg/kg) with or without RESV (20 mg/kg). Serial blood samples were obtained over the following 24 h. Concentrations of SQV in samples were ascertained using high-performance liquid chromatography-tandem mass spectrometry analysis.Results: RESV (1–100 µM) enhanced residual SQV (% of control) in a dose-dependent manner after incubation with intestinal microsomes. RESV (1–100 µM) reduced the accumulation of SQV in MDCKII-MDR1 cells in a concentration-dependent manner. A double peaking phenomenon was observed in the plasma SQV profiles in rats. The first peak of plasma SQV concentration was increased, but the second peak was reduced by coadministration with RESV. The mean AUC0–∞ of SQV was slightly decreased, with no statistical significance probably due to the high individual variation.Conclusion: RESV can alter the plasma SQV concentration profiles, shorten the Tmax of SQV. RESV might also cause a slight decrease tendency in the SQV bioavailability in rats. Keywords: resveratrol, saquinavir, P-glycoprotein, CYP 3A, pharmacokinetic

To assess the safety, tolerability, and preliminary efficacy of NP001, a novel immune regulator of inflammatory monocytes/macrophages, for slowing progression of amyotrophic lateral sclerosis (ALS).This was a phase 2 randomized, double-blind, placebo-contr

An electrically pumped wavelength-tunable InGaN quantum dot (QD) based microcavity (MC) lighter emitter with a large tuning range of 129 nm was demonstrated. The multi-mode emission spectrum was tuned by injected current from 564 nm (yellow-green) to 435 nm (violet). The MC light emitter is featured with a double dielectric distributed Bragg reflector structure and a copper substrate fabricated using substrate transfer and laser lift off techniques. By utilizing an InGaN QD active layer with a tunable broad emission spectrum and a Fabry-Pérot cavity which allows multi-longitudinal mode resonating, the emission spectrum could be tuned among several particular cavity modes, which are decided by the gain enhancement factor. In addition, both the enhancement and suppression of MC emission modes caused by the gain enhancement factor were observed in a single MC device. As the first electrically driven III-V nitride semiconductor based tunable MC light emitter with a tuning range of 129 nm, the device is promising for applications such as in wide-gamut compact displays and projectors. [ABSTRACT FROM AUTHOR]

Phenylpropanoid glycoside acteoside was extracted from the traditional Chinese medicine Scrophularia ningpoenis Hemsl. In the present study, we investigated the effects of acteoside administration on serum uric acid levels in mice rendered hyperuricemic with the uricase inhibitor potassium oxonate. When administered orally for 3 days at doses of 50, 100 and 150 mg/kg, acteoside reduced serum uric acid levels by 15.2, 23.8 and 33.1%, respectively, relative to vehicle-treated hyperuricemic mice. Importantly, in non-hyperuricemic mice, the serum uric acid levels were not affected by acetoside treatment. Acteoside also inhibited mouse liver xanthine dehydrogenase XDH and xanthine oxidase XO activity at all three doses. These results suggest that the hypouricemic action of acteoside may be attributable to its inhibition of XDH/XO activity. [ABSTRACT FROM AUTHOR]

The cornerstone of diagnosis of Alzheimer's disease (AD) is still the clinical criteria for probable and possible AD established by the NINCDS.ADRDA Work Group in 1984, which had survived for over 27 years. However, with the increase in people's knowledge of clinical manifestations and biology of AD, this standard is gradually proving to be insufficient; the early diagnosis of AD is thus particularly important. Therefore, in 2011, the National Institute on Aging and the Alzheimer's Association revised the criteria and integrated biomarker evidence into it. Biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD. According to Consensus Report of the Working Group on Molecular and Biochemical Markers of Alzheimer's Disease, a qualified biomarker for AD should have the following abilities: It should detect a fundamental feature of neuropathology and be validated in neuropathologically confirmed cases, reliably with an sensitivity >80% for detecting AD and a specificity >80% for distinguishing other dementias; be reproducible and non.invasive; and be simple to perform and inexpensive. Alzheimer.associated neuronal thread protein (AD7c-NTP) is a member of "neuronal thread proteins" (NTPs); it can be detected in increased concentration in cortical neurons, brain.tissue extracts, cerebrospinal fluid, and urine in the early course of AD neurodegeneration, and it level is proportional to the degree of dementia, which makes it a promising biomarker for AD. In this review, we have evaluated the feasibility of developing AD7c-NTP as a biomarker for AD. [ABSTRACT FROM AUTHOR]

Hemipteran insects transmit viruses when infesting plants, during which vectors activate salicylic acid (SA)-regulated antiviral defenses. How vector-borne plant viruses circumvent these antiviral defenses is largely unexplored. During co-infections of begomoviruses and betasatellites in plants, betasatellite-encoded βC1 proteins interfere with SA signaling and reduce the activation of antiviral resistance. βC1 inhibits SA-induced degradation of NbNPR3 (Nicotiana benthamiana nonexpressor of pathogenesis-related genes 3), a negative regulator of SA signaling. βC1 does not bind directly to NbNPR3, but regulates NbNPR3 degradation via heat shock protein 90s (NbHSP90s). NbHSP90s bind to both NbNPR3 and βC1 and suppress SA signaling. This viral success strategy appears to be conserved as it is also documented for viral proteins encoded by two aphid-borne viruses. Our findings reveal an exquisite mechanism that facilitates the persistence of vector-borne plant viruses and provide important insights into the intricacies of the virus life cycle., (© 2024. The Author(s).)

Klebsiella pneumoniae, an emerging multidrug-resistant pathogen, exhibits hypermucoviscosity (HMV) as a critical virulence trait mediated by its capsular polysaccharide (CPS). Recent discoveries have determined acetylation as a significant modification for CPS, although its impact on HMV and virulence was previously unknown. This study elucidates the roles of two enzymes: Klebsiella pneumoniae Acetylated CPS Esterase (KpACE), an esterase that removes acetyl groups from CPS, and WcsU, an acetyltransferase that adds acetyl groups to CPS. KpACE is highly upregulated in an ompR-deficient mutant lacking HMV, and its overexpression consistently reduces HMV and diminishes virulence in a mouse model of pneumonia. The esterase domain-containing KpACE effectively deacetylates model sugar substrates and CPS-K2. Site-directed mutagenesis of the conserved catalytic histidine residue at position 370 significantly reduces its enzymatic activity. This reduction correlates with decreased HMV, affecting key virulence traits including biofilm formation and serum resistance. Similarly, a deficiency in the wcsU gene abolishes CPS acetylation, and reduces HMV and virulence. These results highlight the importance of the delicate balance between CPS acetylation by WcsU and deacetylation by KpACE in regulating the pathogenicity of K. pneumoniae. Understanding this balance provides new insights into the modulation of virulence traits and potential therapeutic targets for combating K. pneumoniae infections., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Acute aortic dissection (AD) in pregnancy poses a lethal risk to both mother and fetus. However, well-established therapeutic guidelines are lacking. This study aimed to investigate clinical features, outcomes and optimal management strategies for pregnancy-related AD., Methods: We conducted a retrospective multicentre cohort study including 67 women with acute AD during pregnancy or within 12 weeks postpartum from three major cardiovascular centres in China between 2003 and 2021. Patient characteristics, management strategies and short-term outcomes were analysed., Results: Median age was 31 years, with AD onset at median 32 weeks gestation. Forty-six patients (68.7%) had type A AD, of which 41 underwent immediate surgery. Overall maternal mortality was 10.4% (7/67) and fetal mortality was 26.9% (18/67). Compared with immediate surgery, selective surgery was associated with higher risk of composite maternal and fetal death (adjusted RR: 12.47 (95% CI 3.26 to 47.73); p=0.0002) and fetal death (adjusted RR: 8.77 (95% CI 2.33 to 33.09); p=0.001)., Conclusions: Immediate aortic surgery should be considered for type A AD at any stage of pregnancy or postpartum. For pregnant women with AD before fetal viability, surgical treatment with the fetus in utero should be considered. Management strategies should account for dissection type, gestational age, and fetal viability., Trial Registration Number: NCT05501145., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Depression is a chronic and recurrent disorder with an unknown etiology. Efficacious antidepressant treatments with minimal side effects are urgently needed. Neuroinflammation may contribute to depression, as anti-inflammatory drugs have been shown to alleviate depressive symptoms in clinical practice. Rutin, a naturally occurring flavonoid derived from plants, is abundant in many antidepressant herbs, including Hemerocallis citrina Baroni. Historical Chinese medical texts, including the renowned Compendium of Materia Medica, document H. citrina Baroni as possessing antidepressant properties. Rutin, one of its primary active constituents, is recognized for its anti-inflammatory effects. Despite this, little is known about its specific target and mechanism., Methods: In the present study, molecular docking, and surface plasmon resonance imaging (SPRi) analysis were used to identify the special targets of rutin. Meanwhile, the potential antidepressant effects were evaluated in the chronic social defeat stress (CSDS) paradigm, an animal model of depression. Then, Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), Co-immunoprecipitation (Co-IP) as well as antagonists of PPAR-γ were utilized to investigate the mechanism underlying the antidepressant effect of rutin., Results: Both molecular docking and SPRi analysis showed high docking scores and interactions between rutin and PPAR-γ. In vivo, rutin promoted the nuclear translocation of PPAR-γ in the hippocampus of mice, inhibited NFκB-mediated inflammatory pathways, and subsequently reduced the expression of pro-inflammatory factors (e.g., iNOS, IL-6), aligning with an antidepressant effect. However, this therapeutic effect was attenuated by GW9662, a specific antagonist of PPAR-γ., Conclusion: As a result of activating PPAR-γ and inhibiting NFκB pathway activation, rutin reduces neuroinflammation and exhibits an antidepressant effect. These findings shed light on the antidepressant mechanism of rutin and could be valuable for the development of new antidepressants., 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 GmbH. All rights reserved.)

Preparing stable n-type flexible single-walled carbon nanotube (SWCNT)-based thermoelectric films with high thermoelectric (TE) performance is desirable for self-powering wearable electronics but remains a challenge. Here, the interface regulation and thermoelectric enhancement mechanism of ferrocene derivatives on polyethylenimine/single-walled carbon nanotube (PEI/SWCNT) composite films have been explored by doping ferrocene derivatives (f-Fc-OH) into PEI/SWCNT films. The results show that the introduction of f-Fc-OH leads to the formation of "thorn" structures on the surfaces of SWCNT bundles via hydrophilic and hydrophobic interactions, the generated energy-filtering effect improves the thermoelectric properties of the PEI/SWCNT film, and the f-Fc-OH-doped PEI/SWCNT (f-Fc-OH/PEI/SWCNT) achieves the highest room-temperature power factor of 182.22 ± 8.60 μW m -1 K -2 with a Seebeck coefficient of -64.28 ± 0.96 μV K -1 and the corresponding ZT value of 4.69 × 10 -3 . The Seebeck coefficient retention ratio of the f-Fc-OH/PEI/SWCNT nearly remained 68% after being exposed to air for 3672 h, while the PEI/SWCNT film changed from n-type to p-type after being exposed to air for about 432 h. In addition, the temperature-dependent thermoelectric properties show that the f-Fc-OH/PEI/SWCNT achieves a high power factor of 334.57 μW m -1 K -2 at 353 K. Finally, a flexible TE module consisting of seven pairs of p-n junctions is assembled using the optimum composite film, which produces an open-circuit voltage of 42 mV and a maximum output power of 4.32 μW at a temperature gradient of 60 K. Therefore, this work provides guidance for preparing stable n-type SWCNT-based composite films with enhanced thermoelectric properties, which have potential applications in flexible generators and wearable electronic devices.

A three-component reductive 1,4-dicarbofunctionalization of 1,3-dienes with aziridines and (het)aryl electrophiles was realized. The combination of Ni catalysis with Mn powder as a final reductant enables the direct formation of a Csp 2 -Csp 3 and a Csp 3 -Csp 3 bond at one time. This protocol afforded a convenient approach to the synthesis of β-arylethylamines bearing various functionals and heterocyclic groups. The utility of this reaction was also demonstrated by scale-up preparation, late-stage modification of bioactive molecules, and diverse transformations.

This study was conducted to examine the effects of acupuncture on gut microbiota and expression of NLRP3 inflammasome in the colon in poststroke depression (PSD) model rats. Sprague-Dawley male rats were randomized into four groups: sham surgery group, poststroke depression group, acupuncture group, and probiotics group. Acupuncture therapy at Baihui (GV20), Shenting (GV24), bilateral Zusanli (ST36) acupoints in the acupuncture group and probiotic gavage therapy in the probiotics group were performed once per day for 2 weeks. Behaviors of depression were assessed by using weight measurements, sucrose preference test, open field test, and forced swimming test. Histopathological alterations in the colon were determined by hematoxylin-eosin staining, the expression of NLRP3/ASC/caspase-1 pathway-related proteins was analyzed by western blotting. Serum levels of IL-1β and IL-18 were derived from ELISA. The 16S rRNA gene sequencing was performed to examine and analyze the differences of gut microbiota of rats among all groups. Acupuncture was effective to increase weight and ameliorate depressive-like behaviors in PSD rats. Acupuncture increased the diversity of gut microbiota, upregulated the abundance of Bifidobacteriaceae and Lactobacillaceae, and decreased the relative abundance of Peptostreptococcaceae, Rikenellaceae, Eggerthellaceae, and Streptococcaceae at family level. Acupuncture effectively improved the pathological changes in the colon. Meanwhile, acupuncture reduced NLRP3, ASC, caspase-1 protein expressions in the colon, and serum levels of IL-18 and IL-1β. Acupuncture may reduce depressive-like behaviors of PSD by regulating the gut microbiota and suppressing hyperactivation of NLRP3 inflammasome in the colon. Microbiota-gut-brain axis may be an effective target pathway for acupuncture treatment of PSD., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Parkinson's disease (PD) is characterized by the formation of Lewy bodies (LBs), primarily constituted of α-synuclein (α-Syn). Microglial cells exhibit specific reactivity toward misfolded proteins such as α-Syn. However, the exact clearance mechanism and related molecular targets remain elusive., Methods: BV2 cells, primary microglia from wild-type and MT1 knockout mice, and primary cortical neurons were utilized as experimental models. The study investigated relevant mechanisms by modulating microglial MT1 expression through small RNA interference (RNAi) and lentiviral overexpression techniques. Furthermore, pathological aggregation of α-Syn was induced using pre-formed fibrils (PFF) α-Syn. Co-immunoprecipitation, immunofluorescence, Western blot (WB), and quantitative real-time PCR were used to elucidate the mechanisms of molecular regulation., Results: In this study, we elucidated the regulatory role of the melatonin receptor 1 (MT1) in the microglial phagocytic process. Following MT1 knockout, the ability of microglial cells to engulf latex beads and zymosan particles decreased, subsequently affecting the phagocytic degradation of fibrillar α-Syn by microglial cells. Furthermore, the loss of MT1 receptors in microglial cells exacerbates the aggregation of α-Syn in neurons induced by pre-formed fibrils (PFF) α-Syn. Mechanistically, MT1 influences the phagocytic function of microglial cells by regulating the Rubicon-dependent LC3-associated phagocytosis (LAP) pathway., Conclusion: Taken together, the results suggest the neuroprotective function of microglial cells in clearing α-Syn through MT1-mediated LAP, highlighting the potential key role of MT1 in pathogenic mechanisms associated with α-Syn., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Objective: Levodopa-induced dyskinesia (DYS) adversely affects the quality of life of Parkinson's disease (PD) patients. However, few studies have focused on the relationship between DYS and sleep and electroencephalography (EEG). Our study aimed to establish the objective physiological indicators assessed by polysomnography (PSG) that are associated with DYS in PD patients., Methods: We enrolled 122 patients with PD, divided into two groups: PD with DYS (n = 27) and PD without DYS group (non-DYS, n = 95). The demographics and clinical characteristics and sleep assessment in the two groups were collected. More importantly, overnight six-channel PSG parameters were compared in the two groups. We also compared different bands and brain regions of average power spectral density within each group., Results: Compared with the non-DYS group, the DYS group tended to have a significantly higher percentage of nonrapid eye movement sleep (NREM). Gender, levodopa equivalent daily dose (LEDD), rapid eye movement (REM) sleep (min), and the NREM percentage were positively correlated with the occurrence of DYS. After adjusting for gender, disease duration, LEDD, taking amantadine or not, and Montreal Cognitive Assessment (MoCA), NREM%, N3%, and REM (min), the percentage of NREM sleep (p = 0.035), female (p = 0.002), and LEDD (p = 0.005), and REM sleep time (min) (p = 0.012) were still associated with DYS. There was no significant difference in whole-night different bands of average power spectral density between two groups. There was no significant difference in normalized average power spectral density of slow wave activity (SWA) (0.5-2 Hz, 0.5-4 Hz, and 2-4 Hz) of early and late NREM sleep in the DYS group. Dynamic normalized average power spectral density of SWA of low-frequency (0.5-2 Hz) reduction in the frontal region (p = 0.013) was associated with DYS in logistic regression after adjusting for confounding factors., Conclusion: PD patients with DYS have substantial sleep structure variations. Higher NREM percentage and less REM percentage were observed in PD patients with DYS. Dynamic normalized average power spectral density of low-frequency (0.5-2 Hz) SWA reduction in the frontal area could be a new electrophysiological marker of DYS in PD., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Pathological changes, such as microglia activation in the hippocampus frequently occur in individuals with animal models of depression; however, they may share a common cellular mechanism, such as endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Mitochondria associated membranes (MAMs) are communication platforms between ER and mitochondria. This study aimed to investigate the role of intracellular stress responses, especially structural and functional changes of MAMs in depression., Methods: We used chronic social defeat stress (CSDS) to mimic depression in C57 mice to investigate the pathophysiological changes in the hippocampus associated with depression and assess the antidepressant effect of electroacupuncture (EA). Molecular, histological, and electron microscopic techniques were utilized to study intracellular stress responses, including the ER stress pathway reaction, mitochondrial damage, and structural and functional changes in MAMs in the hippocampus after CSDS. Proteomics technology was employed to explore protein-level changes in MAMs caused by CSDS., Results: CSDS caused mitochondrial dysfunction, ER stress, closer contact between ER and mitochondria, and enrichment of functional protein clusters at MAMs in hippocampus along with depressive-like behaviors. Also, EA showed beneficial effects on intracellular stress responses and depressive-like behaviors in CSDS mice., Limitation: The cellular specificity of MAMs related protein changes in CSDS mice was not explored., Conclusions: In the hippocampus, ER stress and mitochondrial damage occur, along with enriched mitochondria-ER interactions and MAM-related protein enrichment, which may contribute to depression's pathophysiology. EA may improve depression by regulating intracellular stress responses., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The large spectrum of etiologies, severities, and histologic appearances of eosinophilic myocarditis (EoM) poses challenges to its diagnosis and management. Endomyocardial biopsy is the current gold standard for diagnosis. However, cardiovascular magnetic resonance imaging is becoming more frequently used to diagnose acute myocarditis because of enhanced sensitivity when compared to histopathologic examination, and its less invasive nature. We report a complicated case of EoM in a male in his mid-thirties that led to fulminant cardiogenic shock that required immunosuppressive therapy on day 5 of admission and implantation of a left ventricular assist device (LVAD) on day 30. EoM was diagnosed on histopathologic examination of the resected fragment of the left ventricular myocardium. Nine months after the initial presentation, the patient ultimately required heart transplantation. The explanted heart showed minimal residual interstitial inflammation with evidence of mildly active intimal arteritis and patchy areas of interstitial fibrosis. In this report, we describe our patient's clinical features and correlate them with imaging and histopathologic findings to illustrate the difficulty in diagnosing EoM, particularly in this complicated patient that ultimately required heart transplantation. The diagnosis can be challenging due to the variable histopathologic features, clinical presentation, and utilization of therapeutic medications and devices., Competing Interests: Declaration of competing interest 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 Inc. All rights reserved.)

Devices of nanopore sequencing can be highly portable and of low cost. Thus, nanopore sequencing is promising in in-field forensic applications. Previous investigations have demonstrated that nanopore sequencing is feasible for genotyping forensic short tandem repeats (STRs) by using sequencers of Oxford Nanopore Technologies. Recently, Qitan Technology launched a new portable nanopore sequencer and became the second supplier in the world. Here, for the first time, we assess the QNome (QNome-3841) for its accuracy in nanopore sequencing of STRs and compare with MinION (MinION Mk1B). We profile 54 STRs of 21 unrelated individuals and 2800M standard DNA. The overall accuracy for diploid STRs and haploid STRs were 53.5% (378 of 706) and 82.7% (134 of 162), respectively, by using QNome. The accuracies were remarkably lower than those of MinION (diploid STRs, 84.5%; haploid, 90.7%), with a similar amount of sequencing data and identical bioinformatics analysis. Although it was not reliable for diploid STRs typing by using QNome, the haploid STRs were consistently correctly typed. The majority of errors (58.8%) in QNome-based STR typing were one-repeat deviations of repeat units in the error from true allele, related with homopolymers in repeats of STRs., (© 2024 Wiley‐VCH GmbH.)

With the global population continuously rising, efficient bioconversion of inedible agricultural by-products is crucial for human food and energy sustainability. We here propose solid-state fermentation approaches to efficiently convert biopolymers into oligomers/monomers by accelerating the natural degradation process of the versatile Streptomyces sp. strain SCUT-3. Using fish skin as a representative by-product, 54.3 g amino acids and 14.7 g peptides (91 % < 2500 Da) were recovered from 89.0 g protein in 100 g tilapia skin sample by collagenase-overexpressed SCUT-3 for seven days at a 1:4 substrate:liquid ratio. Fish skin collagen hydrolysates exhibited excellent anti-oxidation, anti-hypertension, scratch-repairing, anti-aging, anti-ultraviolet radiation, and anti-inflammation effects on human skin fibroblasts In vitro and zebrafish larvae in vivo, indicating their potential applications in healthcare/skincare and anti-atopic dermatitis. As Laozi said, the divine law follows nature. This study underscores the efficacy of genetically engineered SCUT-3 according to its natural biomass utilization laws in large-scale biopolymer conversion., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Foetal growth restriction (FGR) occurs when a foetus fails to reach its growth potential. This observational study assessed the expression and significance of cell migration-including protein (CEMIP) and aldosterone synthase (CYP11B2) in the serum of pregnant women with FGR., Methods: 40 singleton FGR-suffered pregnant women, as well as 40 normal singleton pregnant women, were enrolled. The expression of CEMIP and CYP11B2 in serum was detected in early pregnancy. The correlations between parameters were evaluated. The predictive variables for FGR were determined. The diagnostic value of CEMIP and CYP11B2 for FGR was analysed., Results: CEMIP and CYP11B2 mRNA expression in the serum of pregnant women with FGR decreased (both P  < 0.001). CEMIP (95%CI: 0.802-0.921, P  < 0.001) and CYP11B2 (95%CI: 0.795-0.907, P  < 0.001) mRNA expression in serum and soluble fms like tyrosine kinase-1 (sFLT1)/placental growth factor (PlGF) ratio (95%CI: 0.866-0.974, P  < 0.001) were independent predictors of FGR, and CEMIP ( r  = -0.578, P  = 0.001) and CYP11B2 ( r  = -0.602, P  < 0.001) mRNA expression in serum were negatively correlated with sFLT1/PlGF ratio. CEMIP (AUC = 0.741) and CYP11B2 (AUC = 0.764) mRNA expression in serum had good diagnostic value for FGR., Conclusion: The expression of CEMIP and CYP11B2 is reduced in the serum of pregnant women with FGR and may become new diagnostic markers for FGR.

Dimethyl oxalate is one of the occupational toxic chemicals and causes strong renal toxicity. On May 16, 2023, a patient with acute dimethyl oxalate poisoning was admitted to Dingxi People's Hospital. The patient presented with nausea, vomiting, lumbar distension, weakness, poor appetite, anuria, and rapidly progressing acute kidney injury. Renal biopsy confirmed acute oxalate nephropathy. After symptomatic supportive treatments such as blood purification, anti-oxidative stress, glucocorticoid, fluid supplementation, alkalized urine, anti-infection, controlling blood pressure, calcium supplementation and anemia correction, the patient's symptoms disappeared, and the kidney function basically returned to normal. This case suggested that the etiology of patients with acute kidney injury must be clearly identified, and renal biopsy was an important examination method. For patients suffering from acute dimethyl oxalate poisoning, comprehensive treatment based on blood purification should be performed as soon as possible, aiming to improve the prognosis.

Pneumococcal disease is caused by Streptococcus pneumoniae , including pneumonia, meningitis and sepsis. Capsular polysaccharides (CPSs) have been shown as effective antigens to stimulate protective immunity against pneumococcal disease. A major step in the production of pneumococcal vaccines is to prepare CPSs that meet strict quality standards in immunogenicity and safety. The major impurities come from bacterial proteins, nucleic acids and cell wall polysaccharides. Traditionally, the impurity level of refined CPSs is reduced by optimization of purification process. In this study, we investigated new aeration strategy and advanced sterilization methods by formaldehyde or β-propiolactone (BPL) to increase the amount of soluble polysaccharide in fermentation supernatant and to prevent bacterial lysis during inactivation. Furthermore, we developed a simplified process for the CPS purification, which involves ultrafiltration and diafiltration, followed by acid and alcohol precipitation, and finally diafiltration and lyophilization to obtain pure polysaccharide. The CPSs prepared from formaldehyde and BPL sterilization contained significantly lower level of residual impurities compared to the refined CPSs obtained from traditional deoxycholate sterilization. Finally, we showed that this novel approach of CPS preparation can be scaled up for polysaccharide vaccine production., Competing Interests: Authors YL, XC, YL, JW, JL, and HZ were employed by Beijing Minhai Biotechnology Co. Ltd. The remaining 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, Cao, Huang, Liu, Wang, Jin, Liu, Zhang and Zheng.)

Cichoric acid (CA), a widely utilized polyphenolic compound in medicine, has garnered significant attention due to its potential health benefits. Sepsis-induced acute kidney disease (AKI) is related with an elevated risk of end-stage kidney disease (ESKD). However, it remains unclear whether CA provides protection against septic AKI. The aim of this study is to investigated the protective effect and possible mechanisms of CA against LPS-induced septic AKI. Sepsis-induced AKI was induced in mice through intraperitoneal injection of lipopolysaccharide (LPS), and RAW264.7 macrophages were incubated with LPS. LPS exposure significantly increased the levels of M1 macrophage biomarkers while reducing the levels of M2 macrophage indicators. This was accompanied by the release of inflammatory factors, superoxide anion production, mitochondrial dysfunction, activation of succinate dehydrogenase (SDH), and subsequent succinate formation. Conversely, pretreatment with CA mitigated these abnormalities. CA attenuated hypoxia-inducible factor-1α (HIF-1α)-induced glycolysis by lifting the NAD + /NADH ratio in macrophages. Additionally, CA disrupted the K (lysine) acetyltransferase 2A (KAT2A)/α-tubulin complex, thereby reducing α-tubulin acetylation and subsequently inactivating the NLRP3 inflammasome. Importantly, administration of CA ameliorated LPS-induced renal pathological damage, apoptosis, inflammation, oxidative stress, and disturbances in mitochondrial function in mice. Overall, CA restrained HIF-1α-mediated glycolysis via inactivation of SDH, leading to NLRP3 inflammasome inactivation and the amelioration of sepsis-induced AKI., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Sepsis often leads to significant morbidity and mortality due to severe myocardial injury. As is known, the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome crucially contributes to septic cardiomyopathy (SCM) by facilitating the secretion of interleukin (IL)-1β and IL-18. The removal of palmitoyl groups from NLRP3 is a crucial step in the activation of the NLRP3 inflammasome. Thus, the potential inhibitors that regulate the palmitoylation and inactivation of NLRP3 may significantly diminish sepsis-induced cardiac dysfunction., Purpose: The present study sought to explore the effects of the prospective flavonoid compounds targeting NLRP3 on SCM and to elucidate the associated underlying mechanisms., Study Design: The palmitoylation and activation of NLRP3 were detected in H9c2 cells and C57BL/6 J mice., Methods/results: Echocardiography, histological staining, western blotting, co-immunoprecipitation, qPCR, ELISA and network pharmacology were used to assess the impact of vaccarin (VAC) on SCM in mice subjected to lipopolysaccharide (LPS) injection. From the collection of 74 compounds, we identified that VAC had the strongest capability to suppress NLRP3 luciferase report gene activity in cardiomyocytes, and the anti-inflammatory characteristics of VAC were further ascertained by the network pharmacology. Exposure of LPS triggered apoptosis, inflammation, oxidative stress, mitochondrial disorder in cardiomyocytes. The detrimental alterations were significantly reversed upon VAC treatment in both septic mice and H9c2 cells exposed to LPS. In vivo experiments demonstrated that VAC treatment alleviated septic myocardial injury, indicated by enhanced cardiac function parameters, preserved cardiac structure, and reduced inflammation/oxidative response. Mechanistically, VAC induced NLRP3 palmitoylation to inactivate NLRP3 inflammasome by acting on zDHHC12. In support, the NLRP3 agonist ATP and the acylation inhibitor 2-bromopalmitate (2-BP) prevented the effects of VAC., Conclusion: Our findings suggest that VAC holds promise in protecting against SCM by mitigating cardiac oxidative stress and inflammation via priming NLRP3 palmitoylation and inactivation. These results lay the solid basis for further assessment of the therapeutic potential of VAC against SCM., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier GmbH.)

Streptococcus spp. are important opportunistic pathogen of bacteremia in both immunocompetent and immunosuppressed patients. A streptococcal strain, designated ST2 T , was isolated from the blood specimen of a bacteremic patient. Comparative analyses of 16S rRNA, rpoB and groEL gene sequences demonstrated that the novel strain ST2 T is a member of the genus Streptococcus. Based on of 16S rRNA gene sequence similarities, the type strains of Streptococcus (S.) parasanguinis (99.2%), S. ilei (98.8%), S. oralis subsp. oralis (97.6%), S. australis (97.5%) and S. sanguinis (97.5%) were the closest neighbours to strain ST2 T . The housekeeping gene sequences (rpoB and groEL) similarities of strain ST2 T to these closely related type strains were 80.4-97.4%, respectively. The complete draft genome of strain ST2 T consisted of 2,155,906 bp with a G + C content of 42.0%. Strain ST2 T has an average nucleotide identity (ANI) value of 94.1 and 81.3% with S. parasanguinis ATCC 15912 T and S. ilei I-G2 T , respectively. The highest in silico DNA-DNA hybridization value with respect to the closest species S. parasanguinis was 55.6%, below the species cut-off of 70% hybridization. The primary cellular fatty acids of strain ST2 T were C 16:0 , C 18:1 ω9c, C 18:0 and C 14:0 . Based on biochemical criteria and molecular genetic evidence, it is proposed that strain ST2 T be assigned to a new species of the genus Streptococcus as Streptococcus taoyuanensis sp. nov. The type strain of Streptococcus taoyuanensis is ST2 T (=NBRC 115928 T  = BCRC 81374 T ) as the type strain., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introducing a core hole significantly alters the electronic structure of a molecule, and various X-ray spectroscopy techniques are available for probing the valence electronic structure in the presence of a core hole. In this study, we visually demonstrate the influence of a core hole on valence excitations by computing the ultraviolet absorption spectra and the shake-up satellites in X-ray photoelectron spectra for pyrrole, furan, and thiophene, as complemented by the natural transition orbital (NTO) analysis over transitions with and without a core hole. Employing equivalent core hole time-dependent density functional theory (ECH-TDDFT) and TDDFT methods, we achieved balanced accuracy in both spectra for reliable comparative analysis. We tracked the same involved valence transition in both spectra, offering a vivid illustration of the core hole effect via the change in corresponding particle NTOs introduced by a 1s core hole on a C α , C β , or O atom. Our analysis deepens the understanding of the core hole effect on valence transitions, a phenomenon ubiquitously observed in general X-ray spectroscopic analyses.

Cardiac myosin-binding protein C (cMyBP-C) is a novel cardiac marker of acute myocardial infarction (AMI) and acute cardiac injuries (ACI). Construction of point-of-care testing techniques capable of sensing cMyBP-C with high sensitivity and precision is urgently needed. Herein, we synthesized an Au@NGQDs@Au/Ag multi-shell nanoUrchins (MSNUs), and then applied it in a colorimetric/SERS dual-mode immunoassay for detection of cMyBP-C. The MSNUs displayed superior stability, colorimetric brightness, and SERS enhancement ability with an enhanced factor of 5.4 × 10 9 , which were beneficial to improve the detection capability of test strips. The developed MSNU-based test strips can achieve an ultrasensitive immunochromatographic assay of cMyBP-C in both colorimetric and SERS modes with the limits of detection as low as 19.3 and 0.77 pg/mL, respectively. Strikingly, this strip was successfully applied to analyze actual plasma samples with significantly better sensitivity, negative predictive value, and accuracy than commercially available gold test strips. Notably, this method possessed a wide range of application scenarios via combining with a color recognizer application named Color Grab on the smartphone, which can meet various needs of different users. Overall, our MSNU-based test strip as a mobile health monitoring tool shows excellent sensitivity, reproducibility, and rapid detection of the cMyBP-C, which holds great potential for the early clinic diagnosis of AMI and ACI.

Benzimidazoles, the representative pharmacophore of fungicides, have excellent antifungal potency, but their simple structure and single site of action have hindered their wider application in agriculture. In order to extend the structural diversity of tubulin-targeted benzimidazoles, novel benzimidazole derivatives were prepared by introducing the attractive pyrimidine pharmacophore. 2-((6-(4-(trifluoromethyl)phenoxy)pyrimidin-4-yl)thio)-1 H -benzo[ d ]imidazole ( A 25 ) exhibited optimal antifungal activity against Sclerotinia sclerotiorum ( S. s. ), affording an excellent half-maximal effective concentration (EC 50 ) of 0.158 μg/mL, which was higher than that of the reference agent carbendazim (EC 50 = 0.594 μg/mL). Pot experiments revealed that compound A 25 (200 μg/mL) had acceptable protective activity (84.7%) and curative activity (78.1%), which were comparable with that of carbendazim (protective activity: 90.8%; curative activity: 69.9%). Molecular docking displayed that multiple hydrogen bonds and π-π interactions could be formed between A 25 and β-tubulin, resulting in a stronger bonding effect than carbendazim. Fluorescence imaging revealed that the structure of intracellular microtubules can be changed significantly after A 25 treatment. Overall, these remarkable antifungal profiles of constructed novel benzimidazole derivatives could facilitate the application of novel microtubule-targeting agents.

Conventional macrolide-lincosamide-streptogramin B-ketolide (MLS B K) antibiotics are unable to counter the growing challenge of antibiotic resistance that is conferred by the constitutive methylation of rRNA base A2058 or its G2058 mutation, while the presence of unmodified A2058 is crucial for high selectivity of traditional MLS B K in targeting pathogens over human cells. The absence of effective modes of action reinforces the prevailing belief that constitutively antibiotic-resistant Staphylococcus aureus remains impervious to existing macrolides including telithromycin. Here, we report the design and synthesis of a novel series of macrolides, featuring the strategic fusion of ketolide and quinolone moieties. Our effort led to the discovery of two potent compounds, MCX-219 and MCX-190, demonstrating enhanced antibacterial efficacy against a broad spectrum of formidable pathogens, including A2058-methylated Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and notably, the clinical Mycoplasma pneumoniae isolates harboring A2058G mutations which are implicated in the recent pneumonia outbreak in China. Mechanistic studies reveal that the modified quinolone moiety of MCX-190 establishes a distinctive secondary binding site within the nascent peptide exit tunnel. Structure-activity relationship analysis underscores the importance of this secondary binding, maintained by a sandwich-like π-π stacking interaction and a water-magnesium bridge, for effective engagement with A2058-methylated ribosomes rather than topoisomerases targeted by quinolone antibiotics. Our findings not only highlight MCX-219 and MCX-190 as promising candidates for next-generation MLS B K antibiotics to combat antibiotic resistance, but also pave the way for the future rational design of the class of MLS B K antibiotics, offering a strategic framework to overcome the challenges posed by escalating antibiotic resistance., (© 2024. The Author(s).)

Objective: Adverse childhood experiences (ACEs) have been associated with a range of adverse health outcomes, with pain being potentially one of them. This population-based cross-sectional study aimed to investigate the associations between Adverse Childhood Experiences (ACEs) and pain in Chinese adults and evaluate whether physical activity and demographic and socioeconomic characteristics modify this associations., Methods: Cross-sectional data from the China Health and Retirement Longitudinal Study (CHARLS), were utilized in this study. A total of 9923 respondents with information on 12 ACE indicators and 15 self-reported body pains were included. Logistic regression models were used to assess associations of the ACEs and pain. Modification of the associations by physical activity, demographic and socioeconomic characteristics was assessed by stratified analyses and tests for interaction., Results: Among the 9923 individuals included in the primary analyses, 5098 (51.4%) males and the mean (SD) age was 61.18 (10·.44) years. Compared with individuals with 0 ACEs, those who with ≥ 5 ACEs had increased risk of single pains and multiple pain. A dose-response association was found between the number of ACEs and the risk of pain (e.g. neck pain for ≥ 5 ACEs vs. none: OR, 1.107; 95% CI, 0.903-1.356; p < 0.001 for trend). In the associations of each body pain with each ACE indicator, most ACE indicators were associated with an increased risk of pain. In addition, physical activity, sociodemographic and socioeconomic characteristics, such as age, sex, educational level, area of residence, childhood economic hardship, did not demonstrate a significant modify on the associations between ACEs and pain., Conclusions: These findings indicate that cumulative ACE exposure is associated with increased odds of self-reported pain in Chinese adults, regardless of adult physical activity, sociodemographic and socioeconomic characteristics., (© 2024. The Author(s).)

Boron-doped graphdiyne (B-GDY) material exhibits an excellent performance in electrocatalysis, ion transport, and energy storage. However, accurately identifying the structures of B-GDY in experiments remains a challenge, hindering further selection of suitable structures with the most ideal performance for various practical applications. In the present work, we employed density functional theory (DFT) to simulate the X-ray photoelectron spectra (XPS) and near-edge X-ray absorption fine-structure (NEXAFS) spectra of pristine graphdiyne (GDY) and six representative single boron-doped graphdiynes at the B and C K-edges to establish the structure-spectroscopy relationship. A notable disparity in the C 1s ionization potentials (IPs) between substituted and adsorbed structures is observed upon doping with a boron atom. By analyzing the C and B 1s NEXAFS spectra on energy positions, spectral widths, spectral intensities, and different spectral profiles, we found that the six single boron-doped graphdiyne configurations can be sensitively identified. Moreover, this study provides a reliable theoretical reference for distinguishing different single boron-doped graphdiyne structures, enabling accurate selection of B-GDY structures for diverse practical applications.

Extracellular ATP (eATP) signaling through the P2X7 receptor pathway is widely believed to trigger NLRP3 inflammasome assembly in microglia, potentially contributing to depression. However, the cellular stress responses of microglia to both eATP and stress itself remain largely unexplored. Mitochondria-associated membranes (MAMs) is a platform facilitating calcium transport between the endoplasmic reticulum (ER) and mitochondria, regulating ER stress responses and mitochondrial homeostasis. This study aims to investigate how MAMs influence microglial reaction and their involvement in the development of depression-like symptoms in response to chronic social defeat stress (CSDS). CSDS induced ER stress, MAMs' modifications, mitochondrial damage, and the formation of the IP3R3-GRP75-VDAC1 complex at the ER-mitochondria interface in hippocampal microglia, all concomitant with depression-like behaviors. Additionally, exposing microglia to eATP to mimic CSDS conditions resulted in analogous outcomes. Furthermore, knocking down GRP75 in BV2 cells impeded ER-mitochondria contact, calcium transfer, ER stress, mitochondrial damage, mitochondrial superoxide production, and NLRP3 inflammasome aggregation induced by eATP. In addition, reduced GRP75 expression in microglia of Cx3cr1 CreER/+ Hspa9 f/+ mice lead to reduce depressive behaviors, decreased NLRP3 inflammasome aggregation, and fewer ER-mitochondria contacts in hippocampal microglia during CSDS. Here, we show the role of MAMs, particularly the formation of a tripartite complex involving IP3R3, GRP75, and VDAC1 within MAMs, in facilitating communication between the ER and mitochondria in microglia, thereby contributing to the development of depression-like phenotypes in male mice., (© 2024. The Author(s).)

Understanding proton transfer (PT) dynamics in condensed phases is crucial in chemistry. We computed a 2D map of N 1s X-ray photoelectron/absorption spectroscopy (XPS/XAS) for an organic donor-acceptor salt crystal against two varying N-H distances to track proton motions. Our results provide a continuous spectroscopic mapping of O-H···N↔O - ··· H + -N processes via hydrogen bonds at both nitrogens, demonstrating the sensitivity of N 1s transient XPS/XAS to hydrogen positions and PT. By reducing the O-H length at N1 by only 0.2 Å, we achieved excellent theory-experiment agreement in both XPS and XAS. Our study highlights the challenge in refining proton positions in experimental crystal structures by periodic geometry optimizations and proposes an alternative scaled snapshot protocol as a more effective approach. This work provides valuable insights into X-ray spectra for correlated PT dynamics in complex crystals, benefiting future experimental studies.

To introduce the modified pharyngeal flap of bilateral muscular rings (BMR), and to discuss the clinical effect of this operation in the correction of moderate and severe velopharyngeal insufficiency. The clinical data of 18 patients who underwent BMR surgery in the Department of Craniofacial Plastic and Aesthetic Surgery, School of Stomatology, The Fourth Military Medical University from May 2019 to July 2021 were retrospectively analyzed. There were 10 males and 8 females, with a median age of 8.5 years (aged from 5 to 34 years). The patients were diagnosed preoperatively with moderate to severe velopharyngeal insufficiency (velopharyngeal closure ratio<0.7). The results of nasopharyngoscopy and speech assessment were compared and analyzed before operation and at the follow-up 6 months after the operation to evaluate the changes in velopharyngeal function and speech. Eighteen patients underwent BMR, 4 patients had snoring (the symptom disappeared after a few weeks in 3 cases), and 2 patients had local erosion of the wound, which delayed healing. Postoperative nasopharyngoscopy showed that all patients achieved comparatively complete velopharyngeal closure, some patients got enhanced lateral pharyngeal wall motility, and all patients got active motility of posterior pharyngeal wall flap. The postoperative speech assessment was significantly improved compared with that before the operation. The preoperative median score was 9 (range 7-12), and the postoperative median score was 2 (range 0-4). The statistical analysis was performed by paired non-parametric Wilcoxon signed rank test, and the difference was statistically significant ( P <0.001). BMR is a reliable method for the treatment of moderate and severe velopharyngeal insufficiency. This technique can achieve functional contraction of the full circumference of the ventilator while preserving the obstructive effect of the posterior pharyngeal wall flap, which is helpful to balance nasal ventilation and velopharyngeal closure and improve the velopharyngeal function of patients.

Objective: To explore the impact of whole blood organophosphate esters (OPEs) flame retardant exposure on thyroid function-related hormones in healthy older adults. Methods: In this panel study, five repeated population-based epidemiological surveys and biological sample collection were conducted from September 2018 to January 2019, with 76 healthy older adults aged 60-69 years in the Dianliu Community of Jinan, Shandong Province. Information on the sociodemographic characteristics, diet, and health status of the respondents was systematically gathered through questionnaires and physical examinations. Fasting venous blood was collected to determine the levels of OPEs, thyroid-stimulating hormone (TSH), triiodothyronine (T 3 ), and thyroxine (T 4 ). A linear mixed-effects model was used to analyze the impact of OPEs exposure on thyroid function-related hormones in healthy older adults. Results: Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 350 person visits. The age of the study participants was (65.07±2.76) years, with 38 participants of both sexes. A total of eight OPEs were included with a detection rate exceeding 50%, and the M ( Q 1 , Q 3 ) for ∑OPEs was 3.85 (2.33, 5.74) ng/ml, with alkyl-OPEs being the major type of OPEs with an M ( Q 1 , Q 3 ) of 1.27 (0.64, 2.50) ng/ml. The M ( Q 1 , Q 3 ) for TSH, T 3 , and T 4 was 3.74 (2.55, 5.69) μIU/ml, 1.32 (1.10, 1.60) ng/ml, and 45.04 (36.96, 53.27) ng/ml, respectively. Linear mixed-effects model showed that TSH was significantly decreased by 9.93% (95% CI :-15.17%, -4.36%) and 11.14% (95% CI :-15.94%, -6.06%) in older adults for each quartile level increase in TnBP and TEHP exposures, respectively. Gender-stratified analysis indicated that TEHP exposure was negatively associated with TSH levels in male older adults, whereas a decrease in TSH levels among female older adults was associated with TnBP exposure. Conclusion: Exposure to whole blood OPEs is associated with decreased TSH levels among healthy older adults, with notable gender differences.

Objective: To determine the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema using Mendelian randomization (MR) analyses. Methods: This study was a secondary data analysis based on the summary data of genome-wide association studies (GWAS), which involved 293 723 participants (educational attainment) from the Social Science Genetics Association Consortium and 462 013 participants [allergic rhinitis and (or) eczema] from the UK Biobank. Genetic variants that were closely related to educational attainment were identified as instrumental variables. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger regression, weighted median method and weighted model-based estimation, were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, in which the odds ratio ( OR ) values were used as indicators. Results: A total of 70 single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results ( P =0.107). In the univariable MR analyses, IVW regression showed that the risk of allergic rhinitis and (or) eczema was OR =1.044 (95% CI : 1.020-1.069, P< 0.001) and OR =1.170 (95% CI : 1.074-1.256, P< 0.001), respectively, for the increase in the duration of education by one year or one standard deviation ( SD ) (3.71 years). In the reverse MR analysis, IVW regression showed little evidence that allergic rhinitis and (or) eczema affected educational attainment ( OR =1.020, 95% CI : 0.927-1.023, P= 0.683). The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW. Conclusion: This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, which means that educational attainment can increase the occurrence of allergic rhinitis and (or) eczema.