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Local anesthetics (LA), as part of multimodal analgesia, have garnered significant interest for their role in delaying the initiation of opioid therapy, reducing postoperative opioid usage, and mitigating both hospitalization duration and related expenses. Despite numerous endeavors to extend the duration of local anesthetic effects, achieving truly satisfactory long-acting analgesia remains elusive. Drawing upon prior investigations, vesicular phospholipid gels (VPGs) emerge as promising candidates for extended-release modalities in small-molecule drug delivery systems. Therefore, we tried to use the amphiphilicity of phospholipids to co-encapsulate levobupivacaine hydrochloride and meloxicam, two drugs with different hydrophilicity, to obtain a long-term synergistic analgesic effect. Initially, the physicochemical attributes of the formulation were characterized, followed by an examination of its in vitro release kinetics, substantiating the viability of extending the release duration of the dual drugs. Sequentially, in vivo investigations encompassing pharmacokinetic profiling and assessment of analgesic efficacy were undertaken, revealing a prolonged release duration of up to 120 h and attainment of optimal postoperative analgesia. Subsequently, inquiries into the mechanism underlying synergistic analgesic effects and safety evaluations pertinent to the delivery strategy were pursued. In summation, we successfully developed a promising formulation to achieve long-acting analgesia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The inflammation causes the destroyed osseointegration at the implant-bone interface, significantly increasing the probability of implant loosening in osteoporotic patients. Currently, inhibiting the differentiation of M1 macrophages and the inflammatory response could be a solution to stabilize the microenvironment of implants. Interestingly, some natural products have anti-inflammatory and anti-polarization effects, which could be a promising candidate for stabilizing the implants' microenvironment in osteoporotic patients. This research aims to explore the inhibitory effect of Urolithin B(UB) on macrophage M1 polarization, which ameliorates inflammation, thus alleviating implant instability. We established an osteoporosis mouse model of implant loosening. The mouse tissues were taken out for morphological analysis, staining analysis, and bone metabolic index analysis. In in vitro experiments, RAW264.7 cells were polarized to M1 macrophages using lipopolysaccharide (LPS) and analyzed by immunofluorescence (IF) staining, Western blot (WB), and flow cytometry. The CSP100 plus chip experiments were used to explore the potential mechanisms behind the inhibiting effects of UB. Through observation of these experiments, UB can improve the osseointegration between the implants and femurs in osteoporotic mice and enhance the stability of implants. The UB can inhibit the differentiation of M1 macrophages and local inflammation via inhibiting the phosphorylation of VEGFR2, which can be further proved by the weakened inhibited effects of UB in macrophages with lentivirus-induced overexpression of VEGFR2. Overall, UB can specifically inhibit the activation of VEGFR2, alleviate local inflammation, and improve the stability of implants in osteoporotic mice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: A competency training index system was designed in public health emergencies for community nurses. The purpose of this approach is to provide community nurses with guidelines for standardized training programs on how to respond to public health emergencies., Methods: Through semi-structured interviews, a literature review, and team discussion, the first draft of competency training index system in public health emergencies for community nurses was formed. The Delphi method was used for two rounds of expert consultation to screen, modify and determine indicators. Finally, the analytic hierarchy process was utilized to calculate the weights of indicators at all levels., Results: A total of 15 expert consultants were included. The effective recovery rate of the two rounds of expert consultation questionnaire was 100%, the expert authority coefficient was 0.880, 0.887, and the Kendall coordination coefficient was 0.172 and 0.171 (p < 0.001). Expert opinions have determined that the final revised competency index system in public health emergencies for community nurses training consists of 2 primary indicators, 10 secondary indicators, and 46 tertiary indicators., Conclusion: The study has developed a competency training index system in public health emergencies for community nurses. This system can serve as a foundation for standardized training in community health service institutions. It is characterized by its high demand, scientific approach, reliability, and rationality., (© 2024 The Author(s). Public Health Nursing published by Wiley Periodicals LLC.)

The effective treatment regimens of triple-negative breast cancer (TNBC), a specific subtype of breast cancer (BC) with proneness to relapse and poor prognosis, are still lacking. Simeprevir (SIM), approved for hepatitis C infection treatment, has been proved to be a competitive drug for the treatment of various solid tumors recently. However, the anti-tumor mechanisms of SIM and therapeutic effects on TNBC are uncertain. In this study, we suggested that SIM effectively restrained the growth of MDA-MB-231 and BT-549 cells, two cell lines from TNBC. The RNA sequencing revealed that ferroptosis signaling was activated in SIM-treated TNBC cells. SIM induced ferroptosis in TNBC cells through reduced glutathione (GSH) levels, increased iron levels, ROS and lipid peroxidation. Mechanistically, SIM promoted the expression of β-TrCP to inhibit the Nrf2/GPX4 axis in TNBC cells, leading to ferroptosis. Moreover, SIM administration into the xenografts formed by MDA-MB-231 dramatically suppressed the tumor progression by inducing ferroptosis in vivo. Collectively, this finding reveals that SIM may serve as a competitive therapeutic strategy to inhibit TNBC., Competing Interests: Declaration of Competing Interest The authors have declared that no competing interest exists., (Copyright © 2024. Published by Elsevier Masson SAS.)

Elucidating the chemical structure and intracellular action mechanisms is still the critical limit for the clinical translation of nanomedicines. Intracellular redox environments originating from cell metabolism are key factors affecting internalized drug efficacy. Herein, we engineer Se-Se/Se-S bond to assemble selenium nanoclusters with intracellular redox environment-driven selective structure. Chemical structure analysis reveals that, the bonding of sulfur atom in intermediates to the two neighboring or interposition selenium atoms in selenium rings is the key internal driving force for nanoparticle cluster formation. This nanocluster can be predominantly transformed to selenocysteine to facilitate selenoproteins synthesis in normal cells, while metabolize to cytotoxic SeO32- based on the oxidative intracellular redox environment of cancer cells. Resultantly, selenium nanoclusters exhibit significant cell proliferation inhibition ability to cancer cells and impressive safety to normal cells. Taken together, this study not only clarifies the chemical nature of the atom engineering of selenium nanocluster, but also elucidates its intracellular redox environment-oriented anticancer mechanism., (© 2024 Wiley‐VCH GmbH.)

Formulating drugs into nanoparticles that target sites of disease can lead to strong therapeutic effects with lower doses of drugs and lower rates of off-target adverse effects. Few ways to target drugs to bone have been described, hampering the treatment of osteoporosis. Here we exploit the ability of alendronate to bind tightly to hydroxyapatite in bone as a tactic to target polymeric micelles loaded with the plant flavonoid icaritin to osteoporotic lesions. The traditional Chinese medicine icaritin, from Herba Epimedii, has previously been shown to inhibit adipogenesis and enhance osteogenesis by bone mesenchymal stem cells, but the compound on its own persists only briefly in the bloodstream. Our delivery system led to stronger inhibition of adipogenesis and activation of osteogenesis in a rat model of osteoporosis than when the icaritin-loaded micelles lacked alendronate. These results establish the feasibility of using alendronate to target osteogenic phytomolecules to sites of bone injury, which may guide the development of effective therapies against osteoporosis and, by extension, other bone disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Superionic conductor-based solid-state electrolytes with preferred crystal structures hold great promise for realizing ultrafast lithium-ion (Li + ) transfer, which is urgently desired for all-solid-state lithium batteries. However, the precise control of crystal growth of superionic conductors is still challenging since the crystals always spontaneously grow to disordered structures with the lowest internal energy to ensure thermodynamic stability. Herein, a coaxial nanowire with a polyvinylpyrrolidone (PVP) sheath and a Li 0.33 La 0.557 TiO 3 (LLTO) precursor core (PVP/LLTO-caNW) is prepared through coaxial electrospinning, followed by sintering into LLTO nanowire with an oriented crystal structure (LLTO-caNW). We demonstrate that the one-dimensional PVP sheath as a sacrificial layer generates uniform and the strongest adsorption ability on the (110) phase among different LLTO crystal planes, which induces the crystal to preferentially grow along the c -axis (the fastest Li + transfer direction) during the nucleation and growth processes. As a result, the prepared LLTO-caNW displays an ultrahigh bulk ionic conductivity of 3.13 × 10 -3 S cm -1 , exceeding most LLTO crystals and approaching the theoretical conductivity. Meanwhile, the oriented crystal growth imparts to LLTO-caNW significantly reduced grain boundary resistance, and the grain-boundary conductivity reaches up to 1.09 × 10 -3 S cm -1 . This endows the composite solid electrolyte with high ionic conduction performance and superior cycle stability in the assembled all-solid-state lithium battery.

Linear chlorinated phosphazene acid is prepared using PCl 5 and NH 4 Cl as raw materials. Using hexaethylcyclotrisiloxane as the monomer, 1,1,3,3-tetramethyldisiloxane or 1,3-divinyl-1,1,3,3-tetramethyldisiloxane as the end-capping agent, and linear chlorinated phosphazene acid as the catalyst, polydiethylsiloxane oligomers terminated with active Si-H or Si-CH=CH 2 groups have been prepared. Using hexaethylcyclotrisiloxane and 1,3,5,7-octamethylcyclotetrasiloxane as comonomers, 1,1,3,3-tetramethyldisiloxane or hexamethyldisiloxane as the end-capping agent, or using hexaethylcyclotrisiloxane and octamethylcyclotetrasiloxane as comonomers, 1,1,3,3-tetramethyldisiloxane as the end-capping agent, copolymers containing active Si-H bonds and dimethylsiloxane segments have been prepared under the catalysis of linear chlorinated phosphazene acid. The effects of catalyst dosage, reaction temperature, reaction time, end-capping agent, and polymerization monomer dosage on polymer yield and structure were investigated. Using 300 ppm of linear chlorinated phosphazene acid, oligomers and copolymers containing an active Si-H bond and diethylsiloxane segment were prepared under mild conditions. The molecular weight of the obtained polymers was close to their designed values, but their PDI values were small. The highest yield of α , ω -bisdimethylsiloxyl-terminated PDES oligomers reached 93%. Using oligomers and copolymers containing Si-H bonds and diethylsiloxane segments as crosslinkers, a silicone gel containing diethylsiloxane segments was prepared by hydrosilylation reaction. With the introduction of a diethylsiloxane segment, the glass transition temperature of the silicone gel decreased relative to that of the PDMS oligomer, but the temperature at 5% weight loss in nitrogen atmosphere decreased from 347 °C to 312 °C. The mechanism of the ring-opening polymerization of hexaethylcyclotrisiloxane catalyzed by linear chlorinated phosphazene acid is also discussed.

Diatomic catalysts, especially those with heteronuclear active sites, have recently attracted significant attention for their advantages over single-atom catalysts in reactions with relatively high energy barrier, e.g. oxygen evolution reaction. Rational design and synthesis of heteronuclear diatomic catalysts are of immense significance but have so far been plagued by the lack of a definitive correlation between structure and catalytic properties. Here, we report macrocyclic precursor constrained strategy to fabricate series of transition metal (MT, Ni, Co, Fe, Mn, or Cu)-noble (MN, Ir or Ru) centers in carbon material. One notable performance trend is observed in the order of Cu-MN < Mn-MN < Fe-MN < MN < Co-MN < Ni-MN. However, the pathway has been not altered, still following the traditional adsorption reaction mechanism. The effect of the MT atoms on the performances could possibly originate from the distinct adsorption/desorption behaviors of key intermediates (i.e. *OH, *O and/or *OOH), strongly implying that ΔG*OOH-ΔG*OH could be used as the performance descriptor. We believe that our work provides useful strategy for synthesis of diatomic active sites with sole coordination configuration and varied composition, and in-depth insight to their catalytic mechanism, which could be used for further optimization of diatomic catalysts towards oxygen electrocatalysis., (© 2024 Wiley‐VCH GmbH.)

Autosomal recessive congenital ichthyosis (ARCI) comprises a series of non-syndromic ichthyoses. Pathogenic variants in several genes associated with ARCI have so far been identified. Notably, the variants in ABCA12 play a pivotal role in the pathology of ARCI. In this study, we report three Chinese families with compound heterozygous variants in the ABCA12 gene, including two novel variants and four reported variants. Clinical and genetic analyses were conducted to explore the genotype-phenotype correlation among the patients. Immunohistochemistry and transcriptome sequencing were utilized to assess the impact of pathogenic ABCA12 variants on skin homeostasis, revealing decreased levels of ABCA12 and claudin-1, alongside increased levels of involucrin and S100A8. In conclusion, our findings contribute to updating the genotype-phenotypic correlation and provide additional evidence for the long-term use of retinoic acid drugs in patients with causative ABCA12 variants., (© 2024 Japanese Dermatological Association.)

Background: Hypertension (HTN) is closely related to endothelial damage. While tianma (TM) and gouqizi (GQZ) have the potential to be effective in the treatment of HTN in traditional Chinese medicine, their main active ingredients and whether its exert synergistic effects and the underlying mechanisms of synergistic effects are still unclear., Objective: This study screened the active ingredients of TM and GQZ, investigated the synergistic effects of the active ingredients and explored possible mechanisms., Methods: The potential targets and mechanisms of TM and GQZ were screened using network pharmacology, and gastrodin (GAS) and gallic acid (GA) were identified as compounds with significant antihypertensive activity. The synergistic effects of the combination of GAS and GA was assessed by measuring biomarkers of AngII-induced human umbilical vein endothelial cell (HUVECs) dysfunction model. Furthermore, the anti-apoptotic and anti-inflammatory effects were evaluated by measuring inflammatory cytokine secretion, and apoptosis-related markers. Finally, key targets of the sphingolipid signaling pathway were experimentally validated by Western blotting., Results: In network pharmacology, the herb-pair exerted a synergetic effect by regulating sphingolipid pathways. The GAS and GA exerted synergistic protective effects in AngII-induced HUVECs injury by improving Nitric Oxide Content (NO) levels, alleviating lactate Endothelin-1 (ET-1), and Thromboxane B2 (TX-B2) release, reducing the secretion of inflammatory factors like interleukin-6 (IL-6), interleukin-1β (IL-1β), Tumor Necrosis Factor Alpha (TNF-α)), decreasing the pro-apoptotic protein BAX, and increasing the anti-apoptotic protein BCL-2. Furthermore, the results showed that the GAS and GA combination could elevate the level of S1PR1 and inhibit the expression of ROCK2 and the phosphorylation of NF-κB, which are key targets involved in sphingolipid pathways., Conclusion: Our study revealed that the combination of GAS and GA could suppress inflammation and apoptosis, which are highly correlated with sphingolipid signaling pathways, making it a potential candidate for the treatment of HTN., Competing Interests: All authors declare that they have no conflicts of interest regarding this study, and all authors agree to be accountable for all aspects of the work, ensuring integrity and accuracy., (© 2024 Wang et al.)

Background: Cervical squamous cell carcinoma (SCC) is the most common type of cervical carcinoma. Usually, the cancer metastasizes through lymphatic or hematogenous dissemination. However, it is uncommon for a superficial spreading of cervical cancer to reach the endometrium, fallopian tubes, and the ovaries., Objectives: In the present study, we report 15 cases of superficial spreading SCC and discuss the possible mechanism involved., Methods: We collected 15 samples diagnosed by histopathology after surgery. Immunostaining, which included P16, P63, CD138, CD34, D2-40, and Ki-67, were performed for all samples., Results: All patients were postmenopausal or perimenopausal women. The commonest clinical presentation was vaginal bleeding in 66.67%. All patients were infected with HPV 16. The endometrium was replaced by high-grade squamous intraepithelial lesion (HSIL), which involved the endometrial gland, even squeezing into the myometrium and forming SCC. Bilateral fallopian tubes and ovaries involvement was in 1/15. A total of 10/15 (66.67%) of the women had disease of stage 1B or less. All SCCs were moderately or poorly differentiated. Immunohistochemistry revealed that the tumor cells were positive for P63 and P16, with a high Ki-67 labeling index. There was CD138 positive expression in varying degrees, which was strongly and diffusely expressed in 6/15 (40.00%)., Conclusion: Superficial spread of cervical cancer towards the endometrium is a rare but cognizable phenomenon, and a guideline for the management of these cases has not been established. Our present findings suggest that multiple factors may interact with each other simultaneously, contributing to this rare disease., 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 Jiang, Han, Chun, Wen and Chen.)

Rare cases of arsenical keratosis are attributed to the ingestion of arsenic-containing traditional Chinese medicines for conditions such as psoriasis. Arsenic is a potent carcinogen, and squamous cell carcinoma is known to develop in arsenical keratosis. A 51-year-old male patient with a 30-year history of psoriasis and a history of arsenic poisoning presented with suppuration, ulceration, and pain one and a half years after trauma to the right thumb. These symptoms had recurred after wound debridement, lesion resection, and pedicle flap transplantation. Histopathological examination of the skin lesions had suggested squamous cell carcinoma, and subsequent PET-CT examination had shown proliferation and enlargement of lymph nodes. Following right forearm amputation and radiofrequency ablation, additional lumps had been observed, but the patient had declined further surgery. Physical examination showed palpable enlarged axillary lymph nodes, which was confirmed by ultrasound. After three cycles of first-line immunotherapy with toripalimab combined with albumin paclitaxel and cisplatin chemotherapy, masses in the right upper arm were reduced. This case highlights the risks of arsenic-containing medicines used for treating psoriasis. Attention should be paid to the use of standardized treatments in psoriasis, as well as the probability of malignant transformation in arsenical keratosis., 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 Liu, Chen, Bai, Zhang and Qi.)

Rationale: Though it is crucial to contribute to patient recovery through access, diversity, continuity and regularity of outpatient care, still today most of these are deemed nonoptimal. Identifying patient profiles based on outpatient service use and quality of care indicators might help formulate more personalized interventions and reduce adverse outcomes., Aims and Objectives: This study aimed to identify profiles of individuals with mental disorders (MDs) patterned after their outpatient care use and quality of care received, and to link those profiles to individual characteristics and subsequent outcomes., Methods: A cohort of 5669 individuals with MDs was considered based on data from the 2013-2014 and 2015-2016 Canadian Community Health Survey, which were linked to administrative data from the Quebec health insurance registry. Latent class analysis generated profiles based on service use over the 12 months preceding each respondent's interview, and comparative analyses were used to associate profiles with sociodemographic and clinical characteristics, and health outcomes over the three following months., Results: Four profiles were identified. Profile 1 (P-1) was labelled 'Low service use'; P-2 'Moderate general practitioner (GP) care and continuity and regularity of care'; P-3 'High GP care, continuity and regularity of care, and low psychiatrist care'; and P-4 'High psychiatrist care and regularity of care, and low GP care'. Profiles 3 and 4 (~50% of the cohort) were provided with better care, but showed worse outcomes, mainly acute care use due to more complex conditions and unmet needs. Profiles 1 and 2 had better outcomes as they showed fewer risk factors such as being younger and having better social conditions., Conclusion: Intensity, diversity and regularity of care were higher in profiles with more complex MDs, chronic physical illnesses, and worse perceived health conditions. Adapting specific interventions for each profile, such as assertive community treatment or intensive case management for Profile 4, is recommended., (© 2024 John Wiley & Sons Ltd.)

Sarcandra glabra is a widely distributed and valuable plant in food and daily chemical industries, and is also a common-used medicinal plant for treating inflammatory diseases and tumors. Rosmarinic acid (RA) with significant pharmacological activity is an abundant and important constituent in S. glabra, however, little information about key enzymes involving the biosynthesis of RA in S. glabra is available and the underlying biosynthesis mechanisms of RA in S. glabra remain undeciphered. Therefore, in this study, by full-length transcriptome sequencing analyses of S. glabra, we screened the RA biosynthesis candidate genes based on sequence similarity and conducted enzymatic function characterization in vitro and in vivo. As a result, a complete set of 7 kinds of enzymes (SgPALs, SgC4H, Sg4CL, SgTATs, SgHPPRs, SgRAS and SgC3H) involving the biosynthesis route of RA from phenylalanine and tyrosine, were identified and fully characterized. This research systematically revealed the complete biosynthesis route of RA in S. glabra, which helps us better understand the process of RA synthesis and accumulation, especially the substrate promiscuities of SgRAS and SgC3H provide the molecular biological basis for the efficient biosynthesis of specific and abundant RA in S. glabra. The 7 kinds of key enzymes revealed in this study can be utilized as tool enzymes for production of RA by synthetic biology methods., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objective: No study has systematically investigated the quality of long-term care delivered to the rural older people with chronic diseases, such as atrial fibrillation (AF) in China. This study aims to provide contemporary data on the prevalence and awareness of AF among the older population in rural China and to evaluate healthcare knowledge and delivery by village doctors., Design: A cross-sectional study., Setting: Rural villages in Daqiao and Xiaoji towns of Jiangsu Province, China., Participants: Rural population aged ≥65 years., Outcome Measures: AF was identified using 12-lead electrocardiography in the first-step (government-led health examination) and single-lead electrocardiography in the second-step (in-house AF screening). Questionnaire surveys were designed for the AF patients and their village doctors., Results: Among 31,342 permanent residents, 12,630 (40.3 %) declined, 7,956 (25.3 %) participated in the first-step and 10,756 (34.3 %) in the second-step. The overall AF detection rate was 4.3 % (810/18,712). Of the 810 AF patients (mean age 76.1±5.9 years; 51.4 % female), 51.5 % were illiterate, only 2.6 % could use smartphone applications, and 8.1 % lived with their children. Common risk factors were older age, men, hypertension, diabetes, prior stroke, vascular disease, and congestive heart failure. Among the 402 patients with known AF, 367 were at high risk of stroke and 10.9 % (40/367) were anticoagulated. Only 17.6 % patients with known hypertension had blood pressure level <140/90 mmHg, and 6.0 % with known diabetes had a fasting blood glucose level ≤6.1 mmol/L. Only 7.3 % (9/122) village doctors reported having the knowledge of integrated care AF management., Conclusions: This study identified AF in 4.3 %, but AF management was suboptimal in rural China. The current village doctor-dominant rural healthcare system is far from delivering standardized AF management for older patients in rural China. There is an urgent need to empower the village doctors in optimising the care of AF patients., Competing Interests: Declaration of competing interest MLC reported receiving lecture fee from Boehringer Ingelheim. All other authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ultraviolet photodetectors (UPDs) based on low-dimensional halide perovskites have undergone rapid development. Here, regulation of the electronic configuration of low-dimensional hybrid perovskites are reported via organic cations for self-powered UPDs. For the first time, it is determine that the rational design of organic cation phenyl alkylammonium can effectively prevent phonon scattering thus increasing charge carrier extraction in low dimensional lead chlorine perovskite thin-films. As a result, the exciton-binding energy can be reduced to 62.91 meV in (PMA) 2 PbCl 4 perovskite films with a charge-carrier mobility of 0.335 cm 2  V -1  s -1 . The fabricated (PMA) 2 PbCl 4 -based self-powered UPDs has achieved a high detectivity of 6.32 × 10 13 jones with a low noise current of 0.35 pA Hz -1/2 under zero bias. A further demonstration of images with high UV to visible light rejection ratio under weak-light illumination of 70 nW cm -2 highlights the feasible potential application of low-dimensional perovskite., (© 2024 Wiley‐VCH GmbH.)

Background: We have previously identified auto-antibody (Ab) to collapsin response mediator protein 2 (CRMP2) in patients with encephalitis. The present study aims to evaluate the pathogenic effects of anti-CRMP2 Ab., Methods: Recombinant CRMP2 protein was injected subcutaneously into mice to establish an active immune mouse model with anti-CRMP2 Ab. Behavioral assessments, histopathological staining, and electrophysiological testing were performed to identify any pathogenic changes., Results: The mice exhibited signs of impaired motor coordination four weeks post-immunization of CRMP2 protein. Moreover, CRMP2 immunized mice for eight weeks showed anxiety-like behaviors indicating by tests of open field and the elevated plus maze. After incubating the CA1 region of hippocampal brain section with the sera from CRMP2 immunized mice, the whole-cell path-clamp recordings showed increased excitability of pyramidal neurons. However, no obvious inflammation and infiltration of immune cells were observed by histopathological analysis. Western blot showed that the phosphorylation levels of CRMP2-Thr514 and -Ser522 were not affected., Conclusion: In an active immunization model with CRMP2 protein, impaired coordination and anxiety-like behaviors were observed. Also, anti-CRMP2 Abs containing sera heightened the excitability of hippocampal pyramidal neurons in vitro, which imply the pathogenic effects of anti-CRMP2 Ab., Competing Interests: Declaration of competing interest 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 Elsevier B.V. All rights reserved.)

Background: Sodium intake reduction is crucial for cardiovascular health, however, its lasting impact on dementia remains unclear., Methods: We included 458,577 UK Biobank participants without dementia at baseline. We estimated 24-h urinary sodium (E24hUNa) using spot urinary parameters and obtained the incidence of all-cause dementia, Alzheimer's disease, and vascular dementia from multiple sources., Results: The mean E24hUNa was 3.0 g (1st-99th percentile: 1.5 g-5.1 g). Over a mean follow-up of 13.6 years, 7886 (1.7 %) participants developed all-cause dementia, including 3763 (0.8 %) Alzheimer's disease and 1851 (0.4 %) vascular dementia. In the restricted cubic spline model, we identify a potential cutoff of 3.13 g for E24hUNa, below which each 1 g decrease in E24hUNa was associated with 21 % (95 % confidence interval [CI] 1.11-1.34) higher all-cause dementia risk and 35 % (95 % CI 1.11-1.63) higher vascular dementia risk (P-value <0.001 for non-linearity). The hazard ratios were 1.15 (95 % CI, 1.07-1.24) for all-cause dementia and 1.21 (95 % CI 1.04-1.40) for vascular dementia among individuals with E24hUNa below 3.13 g compared to those with E24hUNa higher than 3.13 g., Limitations: One of the major limitations is the estimation of 24-h urinary sodium with spot urine samples., Conclusions: An E24hUNa level below 3.13 g, equivalent to 3.37 g daily sodium intake, is associated with increased risks of all-cause and vascular dementia. This exploratory study suggests a potential lower limit below which the risk of dementia increases with a lower sodium level. Future studies are necessary to validate our findings., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In this work, chemical modification of the chitosan with ethyl acetoacetate was performed through a base-catalyzed reaction in which epichlorohydrin facilitated the insertion as well as nucleophilic substitution reaction to graft the 1,3-dioxo moiety across the linear chains of the base biopolymer to establish specificity and selectivity for U(VI) removal. The modified chitosan (EAA-CS) was intercalated into phosphate rich alginate matrix (PASA). Later on, the WO 3 -doped composites with different WO 3 to PASA mass ratio were prepared and characterized using FTIR, XPS, SEM-EDS, XRD, and elemental mapping analysis. WO 3 significantly contributed to chemically stable inorganic-organic composites with improved porous texture. Among the prepared composites, MCPS-3 microspherical beads, having mass ratio of 30.0 % w/w, exhibited excellent sorption capacity for U(VI) at an optimal pH 4.5. The successful U(VI) sorption was validated by the existence of two U4f peaks at 392.25 and 381.36 eV due to U4f 5/2 and U4f 7/2 sub-peaks with an intensity ratio of 3:4, respectively. Batch mode sorption kinetics followed pseudo-second-order rate equation (R 2  ≈ 0.99, q e,th  ≈ 116.88 mg/g, k 2  = 0.86 × 10 -4  g/mg.min -1 ) and equilibrium sorption data aligns with Langmuir (R 2  = 0.99, q m  = 343.85 mg/g at 310 K and pH = 4.5, K L  = 2.00 × 10 -2  L/mg) and Temkin models (R 2  ≈ 0.99). Thermodynamic parameters ΔH o (30.51 kJ/mol), ΔS o (0.19 kJ/mol.K) and ΔG o (-25.64, -26.89, and - 27.91 kJ/mol) at 298, 305, and 310 K, respectively, suggested that the uptake process is feasible, endothermic and spontaneous. Based on these findings, it is reasonable to conclude that MCPS-3 could be a better hydrogel-based biomaterial for appreciable uranium recovery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Dual-atom catalysts (DACs) have been proposed to break the limitation of single-atom catalysts (SACs) in the synergistic activation of multiple molecules and intermediates, offering an additional degree of freedom for catalytic regulation. However, it remains a challenge to synthesize DACs with high uniformity, atomic accuracy, and satisfactory loadings. Herein, we report a facile cascade synthetic strategy for DAC via precise electrostatic interaction control and neighboring vacancy construction. We synthesized well-defined, uniformly dispersed dual Fe sites which were connected by two nitrogen bonds (denoted as Fe-N 2 -Fe). The as-synthesized DAC exhibited superior catalytic performances towards oxygen reduction reaction, including good half-wave potential (0.91 V), high kinetic current density (21.66 mA cm -2 ), and perfect durability. Theoretical calculation revealed that the DAC structure effectively tunes the oxygen adsorption configuration and decreases the cleavage barrier, thereby improving the catalytic kinetics. The DAC-based zinc-air batteries exhibited impressive power densities of 169.8 and 52.18 mW cm -2 at 25 °C and -40 °C, which is 1.7 and 2.0 times higher than those based on Pt/C+Ir/C, respectively. We also demonstrated the universality of our strategy in synthesizing other M-N 2 -M DACs (M=Co, Cu, Ru, Pd, Pt, and Au), facilitating the construction of a DAC library for different catalytic applications., (© 2024 Wiley-VCH GmbH.)

Abnormal angiogenesis and increased vascular permeability of subchondral bone are key mechanisms related to osteoarthritis (OA). However, the precise mechanisms responsible for heightened vascular permeability in OA remain unclear. The present study used proteomics to identify protein expression in damaged subchondral bone compared with normal subchondral bone. The results suggest that Ras homolog family member A (RhoA) may be associated with the vascular permeability of subchondral bone and ferroptosis in OA. The results of analysis of clinical samples indicated a significant increase in expression of RhoA in the subchondral bone of OA. This were consistent with the proteomics findings. We found through western blotting, RT‑PCR, and immunofluorescence that RhoA significantly increased the permeability of endothelial cells (ECs) by inhibiting inter‑EC adhesion proteins (zona occludens‑1, connexin 43 and Vascular endothelial‑Cadherin) and actin filaments. Furthermore, RhoA induced ferroptosis core proteins (glutathione peroxidase 4,  solute carrier family 7 member 11 and acyl‑CoA synthase long‑chain family member 4, ACSL4) by influencing lipid peroxidation and mitochondrial function, leading to ferroptosis of ECs. This suggested an association between RhoA, ferroptosis and vascular permeability. Ferroptosis significantly increased permeability of ECs by inhibiting inter‑EC adhesion proteins. RhoA increased vascular permeability by inducing ferroptosis of ECs. In vivo , inhibition of RhoA and ferroptosis significantly mitigated progression of OA by alleviating cartilage degeneration and subchondral bone remodeling in mice with destabilization of the medial meniscus. In conclusion, the present findings indicated that RhoA enhanced vascular permeability in OA by inducing ferroptosis. This may serve as a novel strategy for the early prevention and treatment of OA.

All-inorganic lead-free CsSnI 3 has shown promising potential in optoelectronic applications, particularly in near-infrared perovskite light-emitting diodes (Pero-LEDs). However, non-radiative recombination induced by defects hinders the optoelectronic properties of CsSnI 3 -based Pero-LEDs, limiting their potential applications. Here, we uncovered that β-CsSnI 3 exhibits higher defect tolerance compared to orthorhombic γ-CsSnI 3 , offering a potential for enhancing the emission efficiency. We further reported on the deposition and stabilization of highly crystalline β-CsSnI 3 films with the assistance of cesium formate to suppress electron-phonon scattering and reduce nonradiative recombination. This leads to an enhanced photoluminescence quantum yield up to ∼10%. As a result, near-infrared LEDs based on β-CsSnI 3 emitters are achieved with a peak external quantum efficiency of 1.81% and excellent stability under a high current injection of 1.0 A cm -2 .

The polar motion (PM, including two parameters PMx and PMy) ultra-short-term prediction (1-10 days) is demanded in the real-time navigation of satellites and spacecrafts. Improving the PMx and PMy ultra-short-term predictions accuracies are a key to optimize the performance of these related applications. Currently, the least squares (LS)+autoregressive (AR) hybrid method is regarded as one of the most capable approaches for ultra-short-term predictions of PMx and PMy. The Kalman filter has proven to be effective in improving the ultra-short-term prediction performance of the LS+AR hybrid method, but the PMx and PMy ultra-short-term predictions accuracies are still not able to satisfy some related applications. In order to improve the performance of PM ultra-short-term prediction, it is worth exploring the combinations of existing methods. Throughout the existing predicted methods, the LS+multivariate autoregressive (MAR) hybrid method by using the Kalman filter has the potential to improve the accuracy of PM ultra-short-term prediction. In addition, a PM prediction performance analysis of the LS+MAR hybrid method by using the Kalman filter, namely the LS+MAR+Kalman hybrid method, is still missing. In this contribution, we proposed the LS+MAR+Kalman hybrid method for PM ultra-short-term prediction. The data sets for PM predictions, which range from 1 to 10 days, have been tested based on the International Earth Rotation and Reference Systems Service Earth Orientation Parameter (IERS EOP) 14 C04 series to assess the performance of the LS+MAR+Kalman hybrid model. The experimental results illustrated that the LS+MAR+Kalman hybrid method can effectively execute PMy ultra-short-term predictions. The improvement of PMy prediction accuracy can rise up to 12.69% for 10-day predictions, and the improvement of ultra-short-term predictions is 7.64% on average.

Background: It is widely known that the incidence rate and short-term mortality of acute myocardial infarctions (AMIs) are generally higher during the winter months. The goal of this study was to determine how the temperature of the environment influences fatal acute myocardial infarctions in Xuzhou., Methods: This observational study used the daily meteorological data and the data on the cause of death from acute myocardial infarction in Xuzhou from January 1, 2018, to December 31, 2020. After controlling meteorological variables and pollutants, the distributed nonlinear lag model (DLNM) was used to estimate the correlation between temperature and lethal AMI., Results: A total of 27,712 patients with fatal AMI were enrolled. 82.4% were over the age of 65, and 50.9% were men. Relative to the reference temperature (15 ℃), the 30-day cumulative RRs of the extremely cold temperature (- 2 ℃) for the general population, women, and people aged 65 years and above were 4.66 (95% CI: 1.76, 12.30), 15.29 (95% CI: 3.94, 59.36), and 7.13 (95% CI: 2.50, 20.35), respectively. The 30-day cumulative RRs of the cold temperature (2 ℃) for the general population, women, and people aged 65 years and above were 2.55 (1.37, 4.75), 12.78 (2.24, 5.36), and 3.15 (1.61, 6.16), respectively. No statistically significant association was observed between high temperatures and the risk of fatal AMI. The influence of the cold effect (1st and 10th) was at its peak on that day, and the entire cold effect persisted for 30 days. Temperature extremes had an effect on the lag patterns of distinct age and gender stratifications., Conclusion: According to this study, the risk of fatal AMI increases significantly in cold weather but not in hot weather. Women above the age of 65 are particularly sensitive to severe weather events. The influence of frigid weather on public health should also be considered., (© 2024. The Author(s).)

This research work focuses on addressing the challenges of electric load forecasting through the combination of Support Vector Regression and Long Short-Term Memory (SVR/LSTM) methodology. The model has been modified by a flexible version of the Gorilla Troops optimization algorithm. The objective of this study is to enhance the precision and effectiveness of load forecasting models by integrating the adaptive functionalities of the Gorilla Troops algorithm within the SVR/LSTM framework. To assess the efficacy of the proposed methodology, a comprehensive series of experiments and evaluations have been undertaken, utilizing authentic data obtained from 200 residential properties located in Texas, United States of America. The dataset comprises historical records of electricity consumption, meteorological data, and other pertinent variables that exert an impact on energy demand. The presence of this general dataset enhances the dependability and inclusiveness of the empirical findings. The proposed methodology was evaluated against various contemporary load forecasting techniques that are widely employed in the industry. The results of a comprehensive evaluation and performance analysis indicate that the modified SVR/LSTM model exhibits superior performance compared to the existing methods in terms of accuracy and robustness. The comparison results unequivocally demonstrate the superiority of the proposed method in accurately forecasting electric load demand., (© 2024. The Author(s).)

The plasminogen activator inhibitor-1 (PAI-1)→mature brain-derived neurotrophic factor (mBDNF) pathway plays a pivotal role in the conversion of probrain-BDNF (ProBDNF) to mBDNF, but its clinical relevance in patients with alcohol use disorder (AUD) remains unknown. Enzyme-linked immunosorbent assays were used to examine the relevant protein levels of components of the PAI-1→mBDNF pathway in plasma samples from three groups of subjects, and statistical analysis was performed using analysis of variance (ANOVA) and one-way repeated-measures ANOVA. Our findings revealed significant alterations induced by alcohol. (1) AUD was associated with significant decreases in tissue plasminogen activator (tPA), mBDNF, and tropomyosin receptor kinase B (TrkB); significant increases in PAI-1, ProBDNF, and P75 neurotrophin receptor (P75NTR); and inhibited conversion of ProBDNF to mBDNF. (2) Following abstinence, the levels of tPA, mBDNF, and TrkB in the AUD group significantly increased, whereas the levels of PAI-1, ProBDNF, and P75NTR significantly decreased, promoting the conversion of ProBDNF to mBDNF. These clinical outcomes collectively suggest that AUD inhibits the conversion of ProBDNF to mBDNF and that abstinence reverses this process. The PAI-1→mBDNF cleavage pathway is hypothesized to be associated with AUD and abstinence treatment., (© 2024. The Author(s).)

In contrast to the central role played by the structure of biomolecules, the complementary force-based view has received little attention in past studies. Here, we proposed a simple method for the force decomposition of multibody interactions and provided some techniques to analyze and visualize the general behavior of forces in proteins. It was shown that atomic forces fluctuate at a magnitude of about 3000 pN, which is huge in the context of cell biology. Remarkably, the average scalar product between atomic force and displacement universally approximates -3 k B T . This is smaller by an order of magnitude than the simple product of their fluctuation magnitudes due to the unexpectedly weak correlation between the directions of force and displacement. The pairwise forces are highly anisotropic, with elongated fluctuation ellipsoids. Residue-residue forces can be attractive or repulsive (despite being more likely to be attractive), forming some kind of tensegrity structure stabilized by a complicated network of forces. Being able to understand and predict the interaction network provides a basis for rational drug design and uncovering molecular recognition mechanisms.

Renal-specific nanoparticulate drug delivery systems have shown great potential in reducing systemic side effects and improving the safety and efficacy of treatments for renal diseases. Here, stearic acid-grafted chitosan oligosaccharide (COS-SA) was synthesized as a renal-targeted carrier due to the high affinity of the 2-glucosamine moiety on COS to the megalin receptor expressed on renal proximal tubular epithelial cells. Specifically, COS-SA/CLT micelles were prepared by encapsulating celastrol (CLT) with COS-SA, and different proportions of human serum albumin (HSA) were then adsorbed onto its surface to explore the interaction between the protein corona and cationic polymeric micelles. Our results showed that a multilayered protein corona, consisting of an inner "hard" corona and an outer "soft" corona, was formed on the surface of COS-SA/CLT@HSA 8 , which was beneficial in preventing its recognition and phagocytosis by macrophages. The formation of HSA protein corona on COS-SA/CLT micelles also increased its accumulation in the renal tubules. Furthermore, the electropositivity of COS-SA/CLT micelles affected the conformation of adsorbed proteins to various degrees. During the adsorption process, the protein corona on the surface of COS-SA/CLT@HSA 1 was partially denatured. Overall, COS-SA/CLT and COS-SA/CLT@HSA micelles demonstrated sufficient safety with renal targeting potential, providing a viable strategy for the management of ischemia/reperfusion-induced acute kidney injury.

Purpose: The aim of this study is to assess the changes and differences in early postoperative binocular accommodative function following femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE)., Methods: In this retrospective study, 120 patients (240 eyes) diagnosed with low-to-moderate and high myopia, who underwent either FS-LASIK or SMILE procedures were included. The assessment encompassed measurements of accommodative facility, accommodation time, relaxation time, and accommodation-to-relaxation ratio using a smart flipper. Measurements were taken preoperatively, as well as at 1 day, 1 week, and 1 month postoperatively. Additionally, the visual fatigue scale score was assessed and compared at the 1 month mark post-surgery. Changes in parameters were quantified by calculating the difference between preoperative values and those recorded at each postoperative time point., Results: At 1 month post-surgery, both FS-LASIK and SMILE procedures demonstrated potential for recovery or even improvement in accommodative facility, accommodation time, relaxation time, and accommodation-to-relaxation ratio compared to preoperative levels. The FS-LASIK group exhibited a greater magnitude of change in accommodative facility postoperatively compared to the SMILE group. In the low-to-moderate myopia subgroup, the FS-LASIK group exhibited lower changes in accommodation time and visual fatigue scale score at 1 month post-surgery compared to the SMILE group, with all associated p -values <0.05., Conclusions: Early postoperative recovery of accommodation function was slower following SMILE compared to FS-LASIK. Additionally, the severity of visual fatigue at 1 month post-surgery was greater in the SMILE group than in the FS-LASIK group. This difference in visual fatigue levels may be attributed to the delayed recovery observed in postoperative SMILE procedures.

Coxsackievirus group B3 (CVB3) belongs to the genus Enteroviruses of the family Picornaviridae and is the main pathogen underlying viral myocarditis (VMC). No specific therapeutic is available for this condition. Argininosuccinate synthase 1 (ASS1) is a key enzyme in the urea cycle that converts citrulline and aspartic acid to argininosuccinate. Here, we found that CVB3 and its capsid protein VP2 inhibit the autophagic degradation of ASS1 and that CVB3 consumes citrulline to upregulate ASS1, triggers urea cycle metabolic reprogramming, and then activates macrophages to develop pro-inflammatory polarization, thereby promoting the occurrence and development of VMC. Conversely, citrulline supplementation to prevent depletion can downregulate ASS1, rescue macrophage polarization, and alleviate the pathogenicity of VMC. These findings provide a new perspective on the occurrence and development of VMC, revealing ASS1 as a potential new target for treating this disease., Importance: Viral myocarditis (VMC) is a common and potentially life-threatening myocardial inflammatory disease, most commonly caused by CVB3 infection. So far, the pathogenesis of VMC caused by CVB3 is mainly focused on two aspects: one is the direct myocardial injury caused by a large number of viral replication in the early stage of infection, and the other is the local immune cell infiltration and inflammatory damage of the myocardium in the adaptive immune response stage. There are few studies on the early innate immunity of CVB3 infection in myocardial tissue, but the appearance of macrophages in the early stage of CVB3 infection suggests that they can play a regulatory role as early innate immune response cells in myocardial tissue. Here, we discovered a possible new mechanism of VMC caused by CVB3, revealed new drug targets for anti-CVB3, and discovered the therapeutic potential of citrulline for VMC., Competing Interests: The authors declare no conflict of interest.

Aims: To explore the effect of postoperative hydrocodone analgesia on inflammatory factors, NSE levels, and cognitive function in elderly patients undergoing hip arthroplasty., Methods: A retrospective analysis was conducted on elderly patients undergoing hip arthroplasty from January 2020 to December 2023. Among them, 43 patients with postoperative hydrocodone analgesia were included in an observation group, and 57 patients without postoperative hydrocodone analgesia in a control group. We compared the differences of general clinical data, inflammatory factors (CRP, WBC and PCT), NSE levels, and cognitive function., Results: After surgery, the VAS scores decreased in both groups compared to before treatment, and the decrease was more significant in the observation group than the control group (P < 0.05). The NSE, WBC, CRP, and PCT level in the control group were significantly higher than those in the observation group at one day, 3 days, and 7 days after surgery (P < 0.05). Moreover, the MMSE score and the serum S100β protein concentration significantly improved in the observation group at one day, 3 days and 7 days after surgery compared to the control group (P < 0.05)., Conclusion: Postoperative hydrocodone analgesia can reduce the release of inflammatory factors after elderly hip replacement surgery, alleviating postoperative pain, and reducing the incidence of early postoperative cognitive impairment., Competing Interests: None., (AJTR Copyright © 2024.)

The rapid expansion of fast fashion has significantly increased microplastic fiber (MPF) release during laundry practices, accounting for approximately one-third of primary microplastics entering the ocean. Currently, a significant gap exists in global-scale research on the release of MPFs from washing textiles. This study introduces an innovative empirical model to assess the spatial distribution of MPF emissions. The model estimates an annual global emission of 5.69 million tons of MPFs from laundry. Of this total, machine washing accounts for the majority (93.7 %), with hand washing contributing the remaining 6.3 %. As the primary source of MPF pollution, Asia's emissions reach 3.71 million tons, far exceeding those of North America (1.18 million tons) and Europe (0.45 million tons). The primary issue is that wastewater management efficiency varies significantly worldwide. In Asia, there is persistently high discharge of MPFs into natural waters, and the removal efficiency of wastewater treatment plants is still comparatively low. In contrast, the United States and many European countries exhibit better MPF retention. The global nature of this challenge mandates international collaboration for comprehensive environmental conservation. Our study provides the first high-resolution global distribution map of MPF emissions and discharge into natural waters, establishing a data foundation for global and regional management of microplastics originating from household laundry sources., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

As histone modification enzymes, EZH2 mediates H3K27 trimethylation (H3K27me3), whereas LSD1 removes methyl groups from H3K4me1/2 and H3K9me1/2. Synergistic anticancer effects of combining inhibitors of these two enzymes are observed in leukemia and prostate cancer. Thus, a series of EZH2/LSD1 dual inhibitors are designed and synthesized to evaluate their anticancer activity. After the structure-activity study, one of the best compounds, ML234 , displayed excellent antiproliferative capacity against prostate cancer cell lines LNCAP, PC3, and 22RV1. Enzymatic assays ascertained that the anticancer potency of ML234 was mediated through coinhibition of EZH2 and LSD1. Moreover, the accumulation of H3K4me2 and H3K9me2 and the decrease of H3K27me3 induced by ML234 were verified by Western blot analysis. More importantly, the compound remarkably suppressed the tumor growth and enhanced the therapeutic efficacy of clinical drug enzalutamide in the 22RV1 xenograft mouse model, indicating that it may have potential as an anticancer agent in prostate cancer.

Objective: Serum amyloid A (SAA) was found to be positively correlated with the activity of Crohn's disease (CD); however, its prognostic value remains uncertain. Here, we examined its predictive ability in newly diagnosed CD and explored genetic association., Methods: This retrospective cohort study included patients newly diagnosed as CD at the First Affiliated Hospital of Sun Yat-sen University between June 2010 and March 2022. We employed receiver operating characteristic curve, Cox proportional hazard regression models and restricted cubic splines to investigate the prognostic performance of SAA for surgery and disease progression. To assess possible causality, a two-sample Mendelian randomisation (MR) of published genome-wide association study data was conducted., Results: During 2187.6 person-years (median age, 28 years, 72.4% male), 87 surgery and 153 disease progression events were documented. A 100-unit increment in SAA level generated 14% higher risk for surgery (adjusted HR (95% CI): 1.14 (1.05-1.23), p=0.001) and 12% for disease progression (1.12 (1.05-1.19), p<0.001). Baseline SAA level ≥89.2 mg/L led to significantly elevated risks for surgery (2.08 (1.31-3.28), p=0.002) and disease progression (1.72 (1.22-2.41), p=0.002). Such associations were assessed as linear. Adding SAA into a scheduled model significantly improved its predictive performances for surgery and disease progression (p for net reclassification indexes and integrated discrimination indexes <0.001). Unfortunately, no genetic causality between SAA and CD was observed in MR analysis. Sensitivity analyses showed robust results., Conclusion: Although causality was not found, baseline SAA level was an independent predictor of surgery and disease progression in newly diagnosed CD, and had additive benefit to existing prediction models., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Multiple embryonic origins give rise to forebrain oligodendrocytes (OLs), yet controversies and uncertainty exist regarding their differential contributions. We established intersectional and subtractional strategies to genetically fate map OLs produced by medial ganglionic eminence/preoptic area (MGE/POA), lateral/caudal ganglionic eminences (LGE/CGE), and dorsal pallium in the mouse brain. We found that, contrary to the canonical view, LGE/CGE-derived OLs make minimum contributions to the neocortex and corpus callosum, but dominate piriform cortex and anterior commissure. Additionally, MGE/POA-derived OLs, instead of being entirely eliminated, make small but sustained contribution to cortex with a distribution pattern distinctive from those derived from the dorsal origin. Our study provides a revised and more comprehensive view of cortical and white matter OL origins, and established valuable new tools and strategies for future OL studies., Competing Interests: YC, ZZ, MS, MZ, LG, MH No competing interests declared, (© 2024, Cai, Zhao, Shi et al.)

Rapid DNA detection is a long-pursuing goal in molecular detection, especially in combating infectious diseases. Loop-mediated isothermal amplification (LAMP) is a robust and prevailing DNA detection method in pathogen detection, which has been drawing broad interest in improving its performance. Herein, we reported a new strategy and developed a new LAMP variant named TLAMP with a superior amplification rate. In this strategy, the turn-back loop primers (TLPs) were devised by ingeniously extending the 5' end of the original loop primer, which conferred the new role of being the inner primer for TLPs while retaining its original function as the loop primer. In theory, based on the bifunctional TLPs, a total of eight basic dumbbell-like structures and four cyclic amplification pathways were produced to significantly enhance the amplification efficiency of TLAMP. With the enhancing effect of TLPs, TLAMP exhibited a significantly reduced amplification-to-result time compared to the conventional six-primer LAMP (typically 1 h), enabling rapid DNA detection within 20 min. Furthermore, TLAMP proved to be about 10 min faster than the fast LAMP variants reported so far, while still presenting comparable sensitivity and higher repeatability. Finally, TLAMP successfully achieved an ultrafast diagnosis of Monkeypox virus (MPXV), capable of detecting as few as 10 copies (0.67copies/μL) of pseudovirus within 20 min using real-time fluorescence assay or within 30 min using a colorimetric assay, suggesting that the proposed TLAMP offers a sensitive, specific, reliable, and, most importantly, ultrafast DNA detection method when facing the challenges posed by infectious diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The wedge effect is known to be influenced by the insertion of the proximal femoral intramedullary nail through the fracture line and the large proximal diameter of the nail. However, the impact of the nail insertion angle (NIA) on the wedge effect remains unclear. This study aimed to investigate: (1) how to evaluate the NIA intraoperatively, (2) whether the NIA is associated with the wedge effect, (3) whether the NIA can serve as a reliable predictor of the wedge effect, (4) which factors affect the NIA, and (5) which surgical techniques can prevent the occurrence of the wedge effect associated with the NIA., Hypothesis: We hypothesized that an excessive NIA is related to the wedge effect and that lateral deviation of the entry point is associated with an excessive NIA., Patients and Methods: Intraoperative fluoroscopy images of patients who underwent intramedullary nail fixation for intertrochanteric hip fractures between 2013 and 2023 were analyzed. NIA and insertion point distance (IPD) were measured on hip anteroposterior radiographs with the guidewire inserted. Femoral shaft lateralization (FSL) and neck-shaft angle (NSA) were measured on hip anteroposterior radiographs before and after nail insertion; differences in FSL and NSA were calculated. A negative difference in FSL combined with a positive difference in NSA indicated the occurrence of the wedge effect. Pearson's correlation test was used to determine relationships between continuous variables (NIA, FSL, NSA, and IPD). Binary logistic regression analyzed the association between NIA and the wedge effect. Receiver operating characteristic (ROC) curve analysis was used to determine the threshold value of NIA, with predictive performance assessed using the area under the ROC curve (AUC). Other potential factors influencing the wedge effect were also examined., Results: A total of 408 patients were included. The mean NIA was 15.61 ± 4.49 °. Post-nail insertion, the average increase in FSL was 3.20 mm, and the average decrease in NSA was 1.90 °. Pearson's correlation test revealed that NIA was negatively correlated with the difference in FSL (R = 0.565, P < 0.001) and positively correlated with the difference in NSA (R = 0.509, P < 0.001). Binary logistic regression showed a significant correlation between NIA and the wedge effect (P < 0.001). ROC analysis indicated that the AUC for NIA was 0.813, with an optimal cutoff point of 14.85 °. IPD was positively correlated with NIA (R = 0.519, P < 0.001). Unstable fractures were associated with increased lateralization of the femoral shaft after nail insertion (P = 0.003)., Discussion: The NIA is positively correlated with the wedge effect in intramedullary nail fixation of intertrochanteric hip fractures. The wedge effect tends to occur when the NIA is >14.85 °, particularly in unstable fractures. Lateral deviation of the entry point is associated with an excessive NIA. Adducting the affected limb, moving the entry point slightly medial and using a medial pusher may help control the NIA to less than 14.85 ° to reduce the wedge effect., Level of Evidence: III., (Copyright © 2024. Published by Elsevier Masson SAS.)

The early diagnosis of liver cancer is crucial for the treatment and depends on the coordinated use of several test procedures. Early diagnosis is crucial for precision therapy in the treatment of the hepatocellular carcinoma (HCC). Therefore, in this study, the NK cell-related gene prediction model was used to provide the basis for precision therapy at the gene level and a novel basis for the treatment of patients with liver cancer. Natural killer (NK) cells have innate abilities to recognize and destroy tumor cells and thus play a crucial function as the "innate counterpart" of cytotoxic T cells. The natural killer (NK) cells is well recognized as a prospective approach for tumor immunotherapy in treating patients with HCC. In this research, we used publicly available databases to collect bioinformatics data of scRNA-seq and RNA-seq from HCC patients. To determine the NK cell-related genes (NKRGs)-based risk profile for HCC, we isolated T and natural killer (NK) cells and subjected them to analysis. Uniform Manifold Approximation and Projection plots were created to show the degree of expression of each marker gene and the distribution of distinct clusters. The connection between the immunotherapy response and the NKRGs-based signature was further analyzed, and the NKRGs-based signature was established. Eventually, a nomogram was developed using the model and clinical features to precisely predict the likelihood of survival. The prognosis of HCC can be accurately predicted using the NKRGs-based prognostic signature, and thorough characterization of the NKRGs signature of HCC may help to interpret the response of HCC to immunotherapy and propose a novel tumor treatment perspective., (© 2024. The Author(s).)

Single-atom catalysts have emerged as cutting-edge hotspots in the field of material science owing to their excellent catalytic performance brought about by well-defined metal single-atom sites (M SASs). However, huge challenges still lie in achieving the rational design and precise synthesis of M SASs. Herein, we report a novel synthesis strategy based on the hetero-charge coupling effect (HCCE) to prepare M SASs loaded on N and S co-doped porous carbon (M 1 /NSC). The proposed strategy was widely applied to prepare 17 types of M 1 /NSC composed of single or multi-metal with the integrated regulation of the coordination environment and electronic structure, exhibiting good universality and flexible adjustability. Furthermore, this strategy provided a low-cost method of efficiently synthesizing M 1 /NSC with high yields, that can produce more than 50 g catalyst at one time, which is key to large-scale production. Among various as-prepared unary M 1 /NSC (M can be Fe, Co, Ni, V, Cr, Mn, Mo, Pd, W, Re, Ir, Pt, or Bi) catalysts, Fe 1 /NSC delivered excellent performance for electrocatalytic nitrate reduction to NH 3 with high NH 3 Faradaic efficiency of 86.6 % and high NH 3 yield rate of 1.50 mg h -1  mg cat. -1 at -0.6 V vs. RHE. Even using Fe 1 /NSC as a cathode in a Zn-nitrate battery, it exhibited a high open circuit voltage of 1.756 V and high energy density of 4.42 mW cm -2 with good cycling stability., (© 2024 Wiley-VCH GmbH.)

Background: The genetic association between urticaria and mental disorders and whether inflammatory cytokines mediate this process remains unclear., Materials and Methods: A Mendelian randomization (MR) approaches to elucidate the causal relationship between urticaria and mental disorders and to validate the mediation of inflammatory cytokines. Genome-wide association study (GWAS) databases used were obtained from Psychiatric Genomics Cooperation (PGC), GWAS Catalog, and FinnGen Consortium. Our study was conducted using inverse variance weighted (IVW) and Bayesian weighted MR (BWMR) methods for joint analysis., Results: The MR results showed that urticaria increased the risk of attention deficit hyperactivity disorder (ADHD) (odds ratio [OR] = $ = $ 1.088, 95% confidence interval [CI]: 1.026-1.154, p = $ = $ 0.0051); cholinergic urticaria increased the risk of bipolar disorder (BD) (OR = $ = $ 1.012, 95% CI: 1.001-1.022, p = $ = $ 0.0274); dermatographic urticaria increased the risk of ADHD (OR = $ = $ 1.057, 95% CI: 1.005-1.112, p = $ = $ 0.0323); idiopathic urticaria increased the risk of schizophrenia (SCZ) (OR = $ = $ 1.057, 95% CI: 1.005-1.112, p = $ = $ 0.0323); other unspecified urticaria increased the risk of ADHD (OR = $ = $ 1.085, 95% CI: 1.023-1.151, p = $ = $ 0.0063). We found that eight inflammatory cytokines were negatively associated with mental disorders and seven inflammatory cytokines were positively associated with mental disorders. Finally, our results suggested that inflammatory cytokines do not act as mediators between urticaria and mental disorders., Conclusions: Our study reveals a causal relationship between urticaria and the increased risk of mental disorders. We suggest that the treatment of urticaria could incorporate psychiatric interventions and mental health assessment of patients., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Objectives: To examine associations between regular statin use and the incidence of depression and anxiety., Methods: This cohort was based on UK Biobank participants without depression/anxiety recruited between 2006 and 2010. The self-reported regular statin use was collected at baseline. Depression and anxiety outcomes were assessed by diagnostic interviews (international classification of diseases codes) and nondiagnostic scales (mental well-being questionnaires). Cox proportional hazards models adjusted for a wide range of confounders were used to estimate associations of statins with incident depression/anxiety., Results: Among 363,551 eligible participants, 55,838 reported regular statin use. During a 13-year follow-up, 14,765 cases of depression and 15,494 cases of anxiety were identified. Compared with non-statin users, statin use was associated with reduced risk of depression (hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.81, 0.94) and anxiety (HR: 0.90, 95% CI: 0.84, 0.97). Effects of statins on depression were consistent in sensitivity analyses and may be less influenced by unmeasured confounders. However, results of online survey data showed that statin use might not be associated with incident anxiety (HR: 0.96, 95% CI: 0.85, 1.09)., Conclusion: Regular statin use was associated with a lower risk of depression. No clear associations between statin use and anxiety were found., 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 Inc. All rights reserved.)

Neurodegenerative diseases like Alzheimer's and Parkinson's disease (AD and PD) are well-known, yet their underlying causes remain unclear. Recent studies have suggested that disruption of ion channels contribute to their pathogenesis. Among these channels, the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, encoded by HCN1-4 genes, are of particular interest due to their role in generating hyperpolarization-activated current (Ih), which is crucial in various neural activities impacting memory and motor functions. A growing body of evidence underscores the pivotal role of HCN in Aβ generation, glial cell function, and ischemia-induced dementia; while HCN is expressed in various regions of the basal ganglia, modulating their functions and influencing motor disorders in PD; neuroinflammation triggered by microglial activation represents a shared pathological mechanism in both AD and PD, in which HCN also plays a significant part. This review delves into the neuronal functions governed by HCN, its roles in the aforementioned pathogenesis, its expression patterns in AD and PD, and discusses potential therapeutic drugs targeting HCN for the treatment of these diseases, aiming to offer a novel perspective and inspire future research endeavors., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gastric cancer (GC) treatment regimens are still unsatisfactory. Recently, Urolithin A (UroA) has gained tremendous momentum due to its anti-tumor properties. However, the therapeutic effect and underlying mechanisms of UroA in GC are unclear. We explored the effects and related mechanisms of UroA on GC both in vivo and in vitro. A Cell Counting Kit-8 was used to determine the influence of UroA on the proliferation of GC cell lines. The Autophagy inhibitor 3-methyladenine (3MA) was employed to clarify the role of autophagy in the anti-tumor effect of UroA. Simultaneously, we detected the core-component proteins involved in autophagy and its downstream pathways. Subsequently, the in vivo anti-tumor effect of UroA was determined using a xenograft mouse model. Western blotting was used to detect the core protein components of the anti-tumor pathways, and 16S rDNA sequencing was used to detect the effect of UroA on the gut microbiota. We found that UroA suppressed tumor progression. The use of 3MA undermined the majority of the inhibitory effect of UroA on tumor cell proliferation, further confirming the importance of autophagy in the anti-tumor effect of UroA. Invigorating of autophagy activated the downstream Hippo pathway, thereby inhibiting the Warburg effect and promoting cell apoptosis. In addition, UroA modulated the composition of the gut microbiota, as indicated by the increase of probiotics and the decrease of pathogenic bacteria. Our research revealed new anti-tumor mechanisms of UroA, which may be a promising candidate for GC treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease marked by joint destruction and functional impairment. Tumor necrosis factor (TNF) plays a critical role in RA pathogenesis. Although TNF-targeting drugs are clinically effective, their need for frequent and long-term administration often results in poor patient adherence and suboptimal outcomes. This study developed a gene therapy approach using engineered adeno-associated virus (AAV) vectors to deliver an anti-TNF agent directly into the joint cavity of RA animal models. Animals receiving this therapy demonstrated sustained improvement in clinical scores, inflammatory markers, and joint tissue health. Immunofluorescence staining revealed that AAV vectors could transduce various cell types, including T cells, type A synoviocytes, and dendritic cells. Our results indicate that a single administration of this gene therapy provided long-term efficacy. This suggests that AAV-mediated anti-TNF gene therapy can offer prolonged relief from clinical symptoms and reduce inflammatory damage in a mouse model of RA. This innovative approach presents a promising new therapy with significant clinical prospects to treat patients with RA.