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Liangrui Zhong,1 Junxian Zheng,2 Qianqian Sun,3 Kemin Wei,2 Yijuan Hu2 1Department of Oncology, Tongde Hospital of Zhejiang Province, Affiliated to Zhejiang Chinese Medical University, 2Department of Chinese Medicine, Zhejiang Academy of Traditional Chinese Medicine, 3Department of Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China Abstract: Radix Tetrastigma hemsleyani flavone (RTHF) is widely used as a traditional herb and has detoxification and anti-inflammatory effects. In this study, we investigated the potential effects of RTHF on the growth and metastasis of human lung adenocarcinoma A549 cells and evaluated its mechanisms. A549 cells were treated with RTHF at various concentrations for different periods. In vitro Cell Counting Kit-8 assay and colony formation methods showed that RTHF had dose- and time-dependent antiproliferation effects on A549 cells. A cell adhesion assay showed that RTHF decreased A549 cell adhesion in a dose-dependent manner. Cell invasion and migration were investigated using the Transwell assay and observed using an inverted microscope; the results showed that cell metastasis was significantly lower in the treatment group than that in the control group (P

Cortical neurons encode both sensory and contextual information, yet it remains unclear how experiences modulate these cortical representations. Here, we demonstrate that trace eyeblink conditioning (TEC), an aversive associative-learning paradigm linking conditioned (CS) with unconditioned stimuli (US), finely tunes cortical coding at both population and single-neuron levels. Initially, we show that the primary somatosensory cortex (S1) is necessary for TEC acquisition, as evidenced by local muscimol administration. At the population level, TEC enhances activity in a small subset (∼20%) of CS- or US-responsive primary neurons (rPNs) while diminishing activity in non-rPNs, including locomotion-tuned or unresponsive PNs. Crucially, TEC learning modulates the encoding of sensory versus contextual information in single rPNs: CS-responsive neurons become less responsive, while US-responsive neurons gain responses to CS. Moreover, we find that the cholinergic pathway, via nicotinic receptors, underlies TEC-induced modulations. These findings suggest that experiences dynamically tune cortical representations through cholinergic pathways., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Functionally diverse devices with artificial neuron and synapse properties are critical for neuromorphic systems. We present a two-terminal artificial leaky-integrate-fire (LIF) neuron based on 6 nm Hf 0.1 Zr 0.9 O 2 (HZO) antiferroelectric (AFE) thin films and develop a synaptic device through work function (WF) engineering. LIF neuron characteristics, including integration, firing, and leakage, are achieved in W/HZO/W devices due to the accumulated polarization and spontaneous depolarization of AFE HZO films. By engineering the top electrode with asymmetric WFs, we found that Au/Ti/HZO/W devices exhibit synaptic weight plasticity, such as paired-pulse facilitation and long-term potentiation/depression, achieving >90% accuracy in digit recognition within constructed artificial neural network systems. These findings suggest that AFE HZO capacitor-based neurons and WF-engineered artificial synapses hold promise for constructing efficient spiking neuron networks and artificial neural networks, thereby advancing neuromorphic computing applications based on emerging AFE HZO devices.

Objective: To evaluate the efficacy, toxicity, and long-term outcomes of PD1 inhibitors plus chemotherapy versus re-irradiation/chemoradiotherapy in patients with unresectable locally recurrent T3-4 nasopharyngeal carcinoma (NPC). Methods: A retrospective analysis was conducted on 42 patients with recurrent nasopharyngeal cancer (NPC) after receiving immunochemotherapy or re-irradiation between February 2018 and May 2022 in Zhejiang Cancer Hospital. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were determined using the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression. Results: With a median follow-up duration of 28.7 months (ranging from 7.2 to 63.9 months), the 3-year OS rate was 23.3% in the re-irradiotherapy (RI) group (N = 24) and 59.6% in the immunochemotherapy (IC) group (N = 18) (p = 0.042). The 3-year PFS, LRFS, and DMFS rates were not significantly different between the two groups (PFS: 45.3% vs. 62.6%, P = 0.482; LRFS: 54.4% vs. 62.6%, P =0.891; DMFS: 89.8% vs. 100.0%, P = 0.489). The univariate analysis revealed that regimen (HR: 0.354, 95% CI: 0.130-0.962, P = 0.042) was significantly correlated with OS. Multivariate analysis also showed that treatment regimen (HR: 0.329, 95% CI: 0.12-0.970, P =0.044) was the only significant prognostic factor associated with OS. The most common late toxicities in the RI group were xerostomia, deafness, and nasopharyngeal necrosis. Of these, nasopharyngeal necrosis was present in 16 patients (66.7%) and in 10 patients (41.7%) at a grade 3 or above. Nasopharyngeal necrosis is the main cause of death in the RI group. In contrast, in the IC group, grade 3 or higher immune-related adverse events or late adverse events were not observed. Conclusions: For unresectable locally recurrent NPC, re-irradiation is an effective treatment; nevertheless, the survival obtains are usually surpassed by serious late complications. For these individuals, chemotherapy in addition to an anti-PD-1 checkpoint inhibitor may be a helpful course of treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Klebsiella pneumoniae (KP) is the second most prevalent Gram-negative bacterium causing bloodstream infections (BSIs). In recent years, the management of BSIs caused by KP has become increasingly complex due to the emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP). Although numerous studies have explored the risk factors for the development of CRKP-BSIs, the mortality of patients with KP-BSIs, and the molecular epidemiological characteristics of CRKP, the variability in data across different populations, countries, and hospitals has led to inconsistent conclusions. In this single-center retrospective observational study, we utilized logistic regression analyses to identify independent risk factors for CRKP-BSIs and factors associated with mortality in KP-BSI patients. Furthermore, a risk factor-based prediction model was developed. CRKP isolates underwent whole-genome sequencing (WGS), followed by an evaluation of microbiological characteristics, including antimicrobial resistance and virulence genes, as well as epidemiological characteristics and phylogenetic analysis., Results: Our study included a total of 134 patients with KP-BSIs, comprising 50 individuals infected with CRKP and 84 with carbapenem-susceptible Klebsiella pneumoniae (CSKP). The independent risk factors for CRKP-BSIs were identified as gastric catheterization (OR = 9.143; CI = 1.357-61.618; P = 0.023), prior ICU hospitalization (OR = 4.642; CI = 1.312-16.422; P = 0.017), and detection of CRKP in non-blood sites (OR = 8.112; CI = 2.130-30.894; P = 0.002). Multivariate analysis revealed that microbiologic eradication after 6 days (OR = 3.569; CI = 1.119-11.387; P = 0.032), high Pitt bacteremia score (OR = 1.609; CI = 1.226-2.111; P = 0.001), and inappropriate empirical treatment after BSIs (OR = 6.756; CI = 1.922-23.753; P = 0.003) were independent risk factors for the 28-day mortality in KP-BSIs. The prediction model confirmed that microbiologic eradication after 6.5 days and a Pitt bacteremia score of 4.5 or higher were significant predictors of the 28-day mortality. Bioinformatics analysis identified ST11 as the predominant CRKP sequence type, with bla KPC-2 as the most prevalent gene variant. CRKP stains carried multiple plasmid-mediated resistance genes along with some virulence genes. Phylogenetic analysis indicated the presence of nosocomial transmission of ST11 CRKP within the ICU., Conclusions: The analysis of risk factors for developing CRKP-BSIs and the association between KP-BSIs and 28-day mortality, along with the development of a risk factor-based prediction model and the characterization of CRKP strains, enhances clinicians' understanding of the pathogens responsible for BSIs. This understanding may help in the timely administration of antibiotic therapy for patients with suspected KP-BSIs, potentially improving outcomes., (© 2024. The Author(s).)

Rationale: College students represent a unique demographic group as they are adults no longer under direct parental care, yet often lack the institutional health support available to more established members of society, which can lead to their health needs being neglected, despite their substantial contributions to blood donation. The objective of this study is to shed light on the health status of college students in Hefei, with a specific focus on transfusion-transmitted diseases. Based on the detailed data analysis, the implementation of some constructive strategies will play a good warning role in improving clinical blood safety and promoting better health monitoring of this population in the future., Aims & Objectives: The study aims to achieve two main objectives: On the one hand, to deepen our understanding of college students' participation in blood donation activities. On the other hand, to propose effective strategies for increasing youth involvement. Additionally, such research aims to afford recommendations for ensuring the safety of clinical blood supplies. Although the strategies and suggestions presented are speculative, they are grounded in the logical analysis of data and relevant theoretical frameworks. Therefore, these recommendations serve as a basis for potential future testing and implementation., Method: The evaluation process for blood samples at the Hefei Blood Bank involves thorough serological testing for hepatitis B and C, HIV, and Treponema pallidum using both Enzyme-Linked Immunosorbent Assay (ELISA) and Nucleic Acid Testing (NAT). HIV reactive samples were further confirmed using Western Blot techniques at an external specialized laboratory. To ensure accuracy, each sample was tested with reagents from two different manufacturers. Moreover, any initially reactive sample was retested with the same reagent to eliminate potential false positives. In cases of conflicting results, alternative reagent kits are utilized for further confirmatory tests. Only samples that consistently show reactive results in consecutive tests are considered positive confirmation samples., Results & Conclusion: Upon analysis of the data set, it was found that out of the total 663,105 donors, 177,089 (26.7%) were identified as college students, with the remaining 486,016 categorized as noncollege students. Our study demonstrated a notably lower prevalence of blood-transmitted infections among college students (0.48%) in contrast to the wider donor population (1.23%), underscoring their potential as safe blood donors. To uphold this level of safety and protect public health, it is crucial to increase disease prevention awareness and advocate for responsible donation practices within this specific demographic. Strengthening confidentiality protocols and expanding education on safe sexual behaviors in university settings are vital actions to cultivate an environment that promotes informed and secure blood donation., In Terms of Specific Infections: The overall group had prevalence rates of 0.44% for hepatitis B, 0.15% for hepatitis C, 0.02% for HIV, and 0.42% for Treponema pallidum. When focusing on the student cohort, the prevalence rates were 0.17% for hepatitis B, 0.04% for hepatitis C, 0.02% for HIV, and 0.23% for Treponema pallidum. Transmissibility through blood transfusion All donors (%) Students (%) Non-students (%) Any infection 1.23 0.48 1.51 HbsAg 0.44 0.17 0.54 Anti-HCV 0.15 0.04 0.19 HIV Ag/Ab 0.02 0.02 0.02 Anti-TP 0.42 0.23 0.49 Individuals with two or more infectious agents occur more than once in all categories. While it leads to numerical over-representation, such overlap is minimal and statistically insignificant., (© 2024 John Wiley & Sons Ltd.)

Persistence reinforces continuous action, which benefits animals in many aspects. Diverse external or internal signals may trigger animals to start a persistent movement. However, it is unclear how the brain decides to persist with current actions by selecting specific information. Using single-unit extracellular recordings and opto-tagging in awake mice, we demonstrated that a group of dorsal mPFC (dmPFC) motor cortex projecting (MP) neurons initiate a persistent movement by selectively encoding contextual information rather than natural valence. Inactivation of dmPFC MP neurons impairs the initiation and reduces neuronal activity in the insular and motor cortex. After the persistent movement is initiated, the dmPFC MP neurons are not required to maintain it. Finally, a computational model suggests that a successive sensory stimulus acts as an input signal for the dmPFC MP neurons to initiate a persistent movement. These results reveal a neural initiation mechanism on the persistent movement., (© 2024. The Author(s).)

Organic electrode materials (OEMs) have gathered extensive attention for aqueous zinc-ion batteries (AZIBs) due to their structural diversity and molecular designability. However, the reported research mainly focuses on the design of the planar configuration of OEMs and does not take into account the important influence of the spatial structure on the electrochemical properties, which seriously hamper the further performance liberation of OEMs. Herein, this work has designed a series of thioether-linked naphthoquinone-derived isomers with tunable spatial structures and applied them as the cathodes in AZIBs. The incomplete conjugated structure of the elaborately engineered isomers can guarantee the independence of the redox reaction of active groups, which contributes to the full utilization of active sites and high redox reversibility. In addition, the position isomerization of naphthoquinones on the benzene rings changes the zincophilic activity and redox kinetics of the isomers, signifying the importance of spatial structure on the electrochemical performance. As a result, the 2,2'-(1,4-phenylenedithio) bis(1,4-naphthoquinone) (p-PNQ) with the smallest steric hindrance and the most independent redox of active sites exhibits a high specific capacity (279 mAh g -1 ), an outstanding rate capability (167 mAh g -1 at 100 A g -1 ), and a long-term cycling lifetime (over 2800 h at 0.05 A g -1 )., (© 2024 Wiley‐VCH GmbH.)

Objective: Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs., Materials and Methods: The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis., Results: According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2-3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level., Conclusion: In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP., (© 2024. The Author(s).)

Prussian blue analogs (PBAs) as insertion-type cathodes have attracted significant attention in various aqueous batteries to accommodate metal or non-metal ions while suffering from serious dissolution and consequent inferior lifespan. Herein, we reveal that the dissolution of PBAs primarily originates from the locally elevated pH of electrolytes that are caused by proton co-insertion during discharge. To address this issue, a water-locking electrolyte (WLE) has been strategically implemented, which interrupts the generation and Grotthuss diffusion of protons by breaking the well-connected hydrogen bonding network in aqueous electrolytes. As a result, the WLE enables the iron hexacyanoferrate to endure over 1000 cycles at a 1C rate and supports a high-voltage decoupled cell with an average voltage of 1.95 V. These findings provide insights for mitigating dissolution problems in electrode materials, thereby enhancing the viability and performance of aqueous batteries., (© 2024 Wiley‐VCH GmbH.)

Realization of dendric signal processing in the human brain is of great significance for spatiotemporal neuromorphic engineering. Here, we proposed an ionic dendrite device with multichannel communication, which could realize synaptic behaviors even under an ultralow action potential of 80 mV. The device not only could simulate one-to-one information transfer of axons but also achieve a many-to-one modulation mode of dendrites. By the adjustment of two presynapses, Pavlov's dog conditioning experiment was learned successfully. Furthermore, the device also could emulate the biological synaptic competition and synaptic cooperation phenomenon through the comodulation of three presynapses, which are crucial for artificial neural network (ANN) implementation. Finally, an ANN was further constructed to realize highly efficient and anti-interference recognition of fashion patterns. By introducing the cooperative device, synaptic weight updates could be improved for higher linearity and larger dynamic regulation range in neuromorphic computing, resulting in higher recognition accuracy and efficiency. Such an artificial dendric device has great application prospects in the processing of more complex information and the construction of an ANN system with more functions.

Labeling the genome and envelope of a virus with multicolor quantum dots (QDs) simultaneously enables real-time monitoring of viral uncoating and genome release, contributing to our understanding of virus infection mechanisms. However, current labeling techniques require genetic modification, which alters the virus's composition and infectivity. To address this, we utilized the CRISPR/Cas13 system and a bioorthogonal metabolic method to label the Japanese encephalitis virus (JEV) genome and envelopes with different-colored QDs in situ. This technique allows one-step two-color labeling of the viral envelope and intraviral genome with QDs harnessing virus infection. In combination with single-virus tracking, we visualized JEV uncoating and genome release in real time near the endoplasmic reticulum of live cells. This labeling strategy allows for real-time visualization of uncoating and genome release at the single-virus level, and it is expected to advance the study of other viral infection mechanisms.

In recent years, memristors have successfully demonstrated their significant potential in artificial neural networks (ANNs) and neuromorphic computing. Nonetheless, ANNs constructed by crossbar arrays suffer from cross-talk issues and low integration densities. Here, we propose an eight-layer three-dimensional (3D) vertical crossbar memristor with an ultrahigh rectify ratio (RR > 10 7 ) and an ultrahigh nonlinearity (>10 5 ) to overcome these limitations, which enables it to reach a >1 Tb array size without reading failure. Furthermore, the proposed 3D RRAM shows advanced endurance (>10 10 cycles), retention (>10 4 s), and uniformity. In addition, several synaptic functions observed in the human brain were mimicked. On the basis of the advanced performance, we constructed a novel 3D ANN, whose learning efficiency and recognition accuracy were enhanced significantly compared with those of conventional single-layer ANNs. These findings hold promise for the development of highly efficient, precise, integrated, and stable VLSI neuromorphic computing systems.

Researching optoelectronic memristors capable of integrating sensory and processing functions is essential for advancing the development of efficient neuromorphic vision. Here, we experimentally demonstrated an all-optical controlled and self-rectifying optoelectronic memristor (OEM) crossbar array with the function of multilevel storage under light stimuli. The NiO/TiO 2 device exhibits an ultrahigh (>10 4 ) rectifying ratio (RR) thus overcoming the presence of sneak current. The reversible conductance modulation without electric signal involvement provides a novel way to realize ultrafast information processing. The proposed OEM array realized synaptic functions observed in the human brain, including long-term potentiation (LTP), long-term depression (LTD), paired-pulse facilitation (PPF), the transition from short-term memory (STM) to long-term memory (LTM), and learning experience behaviors successfully. The authors present a novel OEM crossbar that possesses complete light-modulation capabilities, potentially advancing the future development of efficient neuromorphic vision.

The oxidation characteristics and spontaneous combustion (SC) tendency of raw long-flame coal (RC), water-soaked 200-day coal (S 200 ), pre-oxidized water-soaked coal at 200 °C (O 200 S 200 ), and pre-oxidized soaked coal at 300 °C (O 300 S 200 ) in an oxygen-poor environment were investigated using a programmed warming system. The results show that pre-oxidation water-soaked treatment (PWT) promotes the coal-oxygen complex reaction and increases the rate of coal oxygen consumption (OCR) and the rate of carbon and oxygen compound production. The rate of CO and CO 2 production of the water-soaked (WS) coal increased by 0.329 mol·(cm 3 ·s) -1 and 0.922 mol·(cm 3 ·s) -1 , respectively, compared with that of the original coal sample. PWT reduces the activation energy of coal in the low-temperature oxidation stage (the maximum difference can be up to 110.99 kJ/mol) and enhances the oxidizing and heat-releasing capacity. There was a synergistic effect between the pre-oxidation (PO) and WS treatment, and the lowest comprehensive determination index of the SC propensity of coal in O 200 S 200 samples was 831.92 which was 4.72 lower than that of RC samples, presenting a more SC tendency. Low oxygen concentration has an inhibitory effect on the oxidation characteristic parameters of coal, and the apparent activation energy of the low-temperature oxidation stage of pre-oxidized water-soaked coal (PWC) increased to 206.418 kJ/mol at 3% oxygen concentration. The lower the oxygen concentration of the anoxic environment, the lower the risk of SC of the coal samples. The results of the study can provide theoretical guidance for the identification and prevention of SC disasters in coal seams with shallow burial and close spacing., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

It remains a tremendous challenge to achieve high-efficiency bifunctional electrocatalysts for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) for hydrogen production by water splitting. Herein, a novel hybrid of 0D nickel nanoparticles dispersed on the one-dimensional (1D) molybdenum carbide micropillars embedded in the carbon layers (Ni/Mo 2 C@C) was successfully prepared on nickel foam by a facile pyrolysis strategy. During the synthesis process, the nickel nanoparticles and molybdenum carbide were simultaneously generated under H 2 and C 2 H 2 mixed atmospheres and conformally encapsulated in the carbon layers. Benefiting from the distinctive 0D/1D heterostructure and the synergistic effect of the biphasic Mo 2 C and Ni together with the protective effect of the carbon layer, the reduced activation energy barriers and fast catalytic reaction kinetics can be achieved, resulting in a small overpotential of 96 mV for the HER and 266 mV for the OER at the current density of 10 mA cm -2 together with excellent durability in 1.0 M KOH electrolyte. In addition, using the developed Ni/Mo 2 C@C as both the cathode and anode, the constructed electrolyzer exhibits a small voltage of 1.55 V for the overall water splitting. The novel designed Ni/Mo 2 C@C may give inspiration for the development of efficient bifunctional catalysts with low-cost transition metal elements for water splitting.

Background: Anus preservation has been a challenge in the treatment of patients with low rectal adenocarcinoma (within 5 cm from the anal verge) because it is difficult to spare the anus with its functioning sphincter complex under the safe margin of tumour resection. Patients with dMMR/MSI-H can achieve a favourable complete response (CR) rate by using a single immune checkpoint inhibitor. For patients with pMMR/MSS/MSI-L, intensified neoadjuvant three-drug chemotherapy may be the preferred option for anal preservation. In addition, the watch and wait (W&W) strategy has been proven safe and feasible for patients with rectal cancer who achieve a clinical complete response (cCR). Therefore, we initiated this clinical trial to explore the optimal neoadjuvant treatment pattern for patients with low locally advanced rectal cancer (LARC) with different MMR/MSI statuses, aiming to achieve a higher cCR rate with the W&W strategy and ultimately provide more patients with a chance of anus preservation., Methods: This is a randomised, controlled, open-label, multicentre phase III trial. Patients with clinical stage T2-4 and/or N + tumours located within 5 cm from the anal verge are considered eligible. Based on the results of pathological biopsy, the patients are divided into two groups: dMMR/MSI-H and pMMR/MSS. Patients in the dMMR/MSI-H group will be randomly allocated in a 1:1 ratio to either arm A (monoimmunotherapy) or arm B (short-course radiotherapy followed by monoimmunotherapy). Patients in the pMMR/MSS group will be initially treated with long-term pelvic radiation with concurrent capecitabine combined with irinotecan. Two weeks after the completion of chemoradiotherapy (CRT), the patients will be randomly allocated in a 1:1 ratio to arm C (XELIRI six cycle regime) or arm D (FOLFIRINOX nine cycle regime). The irinotecan dose will be adjusted according to the UGT1A1-genotype. After treatment, a comprehensive assessment will be performed to determine whether a cCR has been achieved. If achieved, the W&W strategy will be adopted; otherwise, total mesorectal excision (TME) will be performed. The primary endpoint is cCR with the maintenance of 12 months at least, determined using digital rectal examination, endoscopy, and rectal MRI or PET/CT as a supplementary method., Discussion: APRAM will explore the best anus preservation model for low LARC, combining the strategies of consolidation chemotherapy, immunotherapy, and short-course radiotherapy, and aims to preserve the anus of more patients using W&W. Our study provides an accurate individual treatment mode based on the MMR/MSI status for patients with low LARC, and more patients will receive the opportunity for anus preservation under our therapeutic strategy, which would transform into long-term benefits., Trial Registration: Clinicaltrials.gov NCT05669092 (Registered 28th Nov 2022)., (© 2024. The Author(s).)

Background: Abnormal tau proteins are independent contributors to cognitive impairment. Nevertheless, not all individuals exposed to high-level tau pathology will develop cognitive dysfunction. We aimed to construct a model to predict cognitive trajectory for this high-risk population., Method: Longitudinal data of 181 non-demented adults (mean age= 73.1; female= 45%), who were determined to have high cerebral burden of abnormal tau by cerebrospinal fluid (CSF) measurements of phosphorylated tau (ptau181) or total tau, were derived from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Cognitive decline was defined as Mini-Mental State Examination scores decline ≥ 3 over three years. A predictive nomogram was constructed using stepwise backward regression method. The discrimination, calibration, and clinical usefulness of the nomogram were evaluated. The model was validated in another 189 non-demented adults via a cross-sectional set (n=149, mean age = 73.9, female = 51%) and a longitudinal set (n= 40, mean age = 75, female = 48%). Finally, the relationships of the calculated risk scores with cognitive decline and risk of Alzheimer's disease were examined during an extended 8-year follow-up., Result: Lower volume of hippocampus (odds ratio [OR] = 0.37, p< 0.001), lower levels of CSF sTREM2 (OR = 0.76, p = 0.003), higher scores of Alzheimer's Disease Assessment Scale-Cognitive (OR = 1.15, p = 0.001) and Functional Activities Questionnaire (OR = 1.16, p = 0.016), and number of APOE ε4 (OR = 1.88, p = 0.039) were associated with higher risk of cognitive decline independent of the amyloid status and were included in the final model. The nomogram had an area of under curve (AUC) value of 0.91 for training set, 0.93 for cross-sectional validation set, and 0.91 for longitudinal validation set. Over the 8-year follow-up, the high-risk group exhibited faster cognitive decline (p< 0.001) and a higher risk of developing Alzheimer's dementia (HR= 6.21, 95% CI= 3.61-10.66, p< 0.001 )., Conclusion: APOE ε4 status, brain reserve capability, neuroinflammatory marker, and neuropsychological scores can help predict cognitive decline in non-demented adults with high burden of tau pathology, independent of the presence of amyloid pathology., Competing Interests: The authors declare that they have no competing interests.

Although the gut microbiota can influence central nervous system (CNS) autoimmune diseases, the contribution of the intestinal epithelium to CNS autoimmunity is less clear. Here, we showed that intestinal epithelial dopamine D2 receptors (IEC DRD2) promoted sex-specific disease progression in an animal model of multiple sclerosis. Female mice lacking Drd2 selectively in intestinal epithelial cells showed a blunted inflammatory response in the CNS and reduced disease progression. In contrast, overexpression or activation of IEC DRD2 by phenylethylamine administration exacerbated disease severity. This was accompanied by altered lysozyme expression and gut microbiota composition, including reduced abundance of Lactobacillus species. Furthermore, treatment with N2-acetyl-L-lysine, a metabolite derived from Lactobacillus, suppressed microglial activation and neurodegeneration. Taken together, our study indicates that IEC DRD2 hyperactivity impacts gut microbial abundances and increases susceptibility to CNS autoimmune diseases in a female-biased manner, opening up future avenues for sex-specific interventions of CNS autoimmune diseases., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A molecular diagnostic assay which could be stored at room temperature was developed to rapidly detect Mycobacterium tuberculosis (MTB) based on loop-mediated isothermal amplification (LAMP) technology and dry-reagent process. LAMP uses 4 or 6 primers and Bst DNA polymerase to amplify DNA at a constant temperature. The results showed that the LAMP assay could detect the amplification of IS6110 target gene within 20 min using real-time fluorescence signal detection. The sensitive of LAMP assay was similar to the PCR technology while the precision of PCR was better than LAMP (coefficient of variation, LAMP 18.9%, PCR 3.4%), meaning LAMP was more suitable for qualitative detection. The LAMP assay did not amplify DNA of other 10 types of pathogens, including Neisseria meningitidis , Haemophilus influenzae , Staphylococcus aureus , Streptococcus pneumoniae , Rubivirus , mumps virus, adenovirus (type 3), adenovirus (type 7), respiratory syncytial virus B and parainfluenza virus type 2, indicating a good specificity. Furthermore, a dry-reagent assay was developed using air-drying and freeze-drying process. The performance of dried reagents did not change after 10 days storage at 50 ℃, meaning the dried reagents could be stored at room temperature (25 ℃) for more than six months. The dry-reagent LAMP assay also successfully amplified MTB DNA from several clinical samples within 20 min. In conclusion, the developed LAMP assay together with isothermal amplifier could rapidly detection MTB.

With the normalization of deep mining, the risk of residual coal spontaneous combustion (CSC) in deeply mined areas has gradually increased. To investigate the thermal characteristics and microgroup transformation mechanisms during the secondary oxidation of deep-well oxidized coal, a deep-well oxidation process was simulated in a synchronous thermal analyzer, and the thermal parameters of the oxidized coal were tested. The correlated transformation pathways of microscopic active groups was studied by electron paramagnetic resonance (EPR) and in situ diffuse reflectance (in situ FTIR) experiments during the reoxidation of oxidized coal. The results showed that with increasing deep-well ambient temperature and oxidation temperature, the characteristic temperature of coal gradually decreased, exothermic heat release gradually increased, and active aliphatic structures and -OH, -CHO and other active functional groups gradually accumulated and became distributed more uniformly. When the thermal conditions and oxidation temperature were very high (> 160 °C), the active free radicals in the oxidized coal were rapidly consumed, resulting in a gradual decrease in the characteristic temperature and heat release during the secondary oxidation process, while the contents of peroxy and carboxyl groups continued to increase. In the slow oxidation stage of oxidized coal, methyl groups were mainly transformed with hydroxyl and peroxide groups (r > 0.96), and the associated oxidative consumption of -CHO and -COOH mainly occurred in the rapid oxidation stage (r > 0.99). Geminal diols and peroxy groups are important intermediates in the coal-oxygen composite reaction process. With an increase in the deep-well temperature and initial oxidation temperature, the reoxidation tendency and heat release capacity of residual coal in the goaf gradually increased, and the risk of CSC intensified. The research results provide a theoretical reference for the prevention and control of coal fires in deep mines and play an important role in guiding environmental management and gas emissions reduction measures in mining areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationship that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To observe the application effect of double-tube negative pressure drainage in the repair of refractory wounds., Methods: From January 2020 to April 2023, 50 patients undergoing refractory wound repair in the Department of Burn and Plastic Surgery of Jingjiang People's Hospital, Jiangsu were selected. According to different treatment methods, they were divided into an observation group and a control group, with 25 patients in each group. The observation group was treated with double-tube negative pressure drainage inside and outside the wound, while the control group was treated with negative pressure drainage inside the wound. By two-week observation, the wound healing status and complication rate after treatment, as well as the wound bacterial clearance rate, wound pain score and patient satisfaction 3, 7 and 14 d after treatment were compared between the two groups. Statistical analysis was carried out to determine the efficacy., Results: After treatment for two weeks, the observation group showed a higher grade A healing rate (92% vs. 60%, X 2  = 7.018, P = 0.008), a higher wound bacterial clearance rate (100% vs. 76%, X 2  = 6.818, P = 0.03), a lower pain score (1.44 ± 0.51 vs. 2.36 ± 0.49, t = -6.53, P < 0.01), a higher patient satisfaction score (8.48 ± 0.96 vs. 6.64 ± 0.95, t = 6.80, P < 0.01), and a lower complication rate (8% vs. 40%, X 2 = 7.018, P = 0.008) compared with the control group., Conclusion: Double-tube negative pressure drainage has a significant application effect in the repair of refractory wounds. It can accelerate wound healing, shorten treatment time, effectively eliminate bacteria, relieve wound infection, reduce complications, alleviate pain and improve patient satisfaction. Therefore, the application, promotion and research of double-tube negative pressure drainage should be strengthened in clinical practice., (© 2023 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

The slow reaction kinetics and structural instability of organic electrode materials limit the further performance improvement of aqueous zinc-organic batteries. Herein, we have synthesized a Z-folded hydroxyl polymer polytetrafluorohydroquinone (PTFHQ) with inert hydroxyl groups that could be partially oxidized to the active carbonyl groups through the in situ activation process and then undertake the storage/release of Zn 2+ . In the activated PTFHQ, the hydroxyl groups and S atoms enlarge the electronegativity region near the electrochemically active carbonyl groups, enhancing their electrochemical activity. Simultaneously, the residual hydroxyl groups could act as hydrophilic groups to enhance the electrolyte wettability while ensuring the stability of the polymer chain in the electrolyte. Also, the Z-folded structure of PTFHQ plays an important role in reversible binding with Zn 2+ and fast ion diffusion. All these benefits make the activated PTFHQ exhibit a high specific capacity of 215 mAh g -1 at 0.1 A g -1 , over 3400 stable cycles with a capacity retention of 92 %, and an outstanding rate capability of 196 mAh g -1 at 20 A g -1 ., (© 2023 Wiley-VCH GmbH.)

A novel ultra-compact four-port multiple-input-multiple-output (MIMO) cylindrical dielectric resonator antenna (DRA) with improved isolation is proposed for WLAN applications in this paper. The antenna is originally radiated with the assistance of two different excitation mechanisms to generate decoupled orthogonal modes. To further diminish the coupling field and improve the isolation, a suitable U-shaped slot is created on the common ground plane. Two additional rectangular slits are also etched to adjust the impedance matching of other ports. To better reveal the operating mechanism of the decoupling scheme, the common mode (CM) and differential mode (DM) impedance analysis methods between DRA ports are presented. The etched U-shaped slot can tune the impedance of CM and DM to be consistent to realize the decoupling. The antenna is simulated, fabricated, and tested to verify the decoupling mechanism. The results demonstrate that the isolation between ports 1 and 2 is enhanced from 5 dB to 23 dB, and other ports exhibit low coupling of better than 12 dB. Moreover, the antenna with the full size of 30 × 30 × 8.1 mm 3 can be used either as a four-port DRA with a bandwidth of 300 MHz or as a two-port DRA with a bandwidth of 700 MHz, at a center frequency of 5.6 GHz.

Hypothesis: Unlike noble metals, the oxygen reduction reaction (ORR) behavior on Ti is more complicated due to its spontaneously formed oxide film. This film results in sluggish ORR kinetics and tends to be reduced within ORR potential region, causing the weak and multi-reaction coupled current. Though Ti is being used in chemical and biological fields, its ORR research is still underexplored., Experiments: We innovatively employed the modified reactive tip generation-substrate collection (RTG/SC) mode of scanning electrochemical microscopy (SECM) with high efficiency of 97.2 % to quantitatively study the effects of film characteristics, solution environment (pH, anion, dissolved oxygen), and applied potential on the ORR activity and selectivity of Ti. Then, density functional theory (DFT) and molecular dynamics (MD) analyses were employed to elucidate its ORR behavior., Findings: On highly reduced Ti, film properties dominate ORR behavior with promoted 4e - selectivity. Rapid film regeneration in alkaline/O 2 -saturated conditions inhibits ORR activity. Besides, ORR is sensitive to anion species in neutral solutions while showing enhanced 4e - reduction in alkaline media. All the improved 4e - selectivities originate from the hydrogen bond/electrostatic stabilization effect, while the decayed ORR activity by Cl - arises from the suppressed O 2 adsorption. This work provides theoretical support and possible guidance for ORR research on oxide-covered metals., 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 © 2023 Elsevier Inc. All rights reserved.)

Purpose: All-inside anterior talofibular ligament (ATFL) repair using anchors is frequently used to manage chronic lateral ankle instability (CLAI) with satisfactory functional outcomes. It remains unclear whether there are differences in the functional results between the use of one or two double-loaded anchors., Methods: This retrospective cohort study included 59 CLAI patients who underwent an all-inside arthroscopic ATFL repair procedure from 2017 to 2019. Patients were divided into two groups according to the number of anchors used. In the one-anchor group (n = 32), the ATFL was repaired with one double-loaded suture anchor. In the two-anchors group (n = 27), the ATFL was repaired with two double-loaded suture anchors. At the last follow-up time point, the Visual Analogue Scale (VAS) scores, American Orthopedic Foot and Ankle Society (AOFAS) scores, Karlsson Ankle Function Score (KAFS), Anterior Talar Translation (ATT), Active Joint Position Sense (AJPS), and the rate of return to sports in both groups were compared., Results: All the patients were followed up for at least 24 months. Improvement in the functional results (VAS, AOFAS, KAFS, ATT, and AJPS) were recorded at the final follow-up time point. No significant differences were observed regarding VAS, AOFAS, KAFS, ATT, and AJPS between the two groups., Conclusion: In patients with CLAI undergoing all-inside arthroscopic ATFL repair, the use of either one or two double-loaded suture anchors produces comparable and predictably good functional outcomes., Level of Evidence: Level III., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Cuproptosis, a new type of programmed cell death (PCD), is closely related to cellular tricarboxylic acid cycle and cellular respiration, while hypoxia can modulate PCD. However, their combined contribution to tumor subtyping remains unexplored. Here, we applied a multi-omics approach to classify TCGA&#95;COADREAD based on cuproptosis and hypoxia. The classification was validated in three colorectal cancer (CRC) cohorts and extended to a pan-cancer analysis. The results demonstrated that pan-cancers, including CRC, could be divided into three distinct subgroups (cuproptosis-hypoxia subtypes, CHSs): CHS1 had active metabolism and poor immune infiltration but low fibrosis; CHS3 had contrasting characteristics with CHS1; CHS2 was intermediate. CHS1 may respond well to cuproptosis inducers, and CHS3 may benefit from a combination of immunotherapy and anti-fibrosis/anti-hypoxia therapies. In CRC, the CHSs also showed a significant difference in prognosis and sensitivity to classic drugs. Organoid-based drug sensitivity assays validated the results of transcriptomics. Cell-based assays indicated that masitinib and simvastatin had specific effects on CHS1 and CHS3, respectively. A user-friendly website based on the classifier was developed (https://fan-app.shinyapps.io/chs&#95;classifier/) for accessibility. Overall, the classifier based on cuproptosis and hypoxia was applicable to most pan-cancers and could aid in personalized cancer therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Organic materials have attracted much attention in aqueous zinc-ion batteries (AZIBs) due to their sustainability and structure-designable, but their further development is hindered by the high solubility, poor conductivity, and low utilization of active groups, resulting in poor cycling stability, terrible rate capability, and low capacity. In order to solve these three major obstacles, a novel organic host, benzo[b]naphtho[2',3':5,6][1,4]dithiino[2,3-i]thianthrene-5,7,9,14,16,18-hexone (BNDTH), with abundant electroactive groups and stable extended π-conjugated structure is synthesized and composited with reduced graphene oxide (RGO) through a solvent exchange composition method to act as the cathode material for AZIBs. The well-designed BNDTH/RGO composite exhibits a high capacity of 296 mAh g -1 (nearly a full utilization of the active groups), superior rate capability of 120 mAh g -1 , and a long lifetime of 58 000 cycles with a capacity retention of 65% at 10 A g -1 . Such excellent performance can be attributed to the ingenious structural design of the active molecule, as well as the unique solvent exchange composition strategy that enables effective dispersion of excess charge on the active molecule during discharge/charge process. This work provides important insights for the rational design of organic cathode materials and has significant guidance for realizing ideal high performance in AZIBs., (© 2023 Wiley-VCH GmbH.)

Hafnium oxide (HfO 2 )-based ferroelectric tunnel junctions (FTJs) have been extensively evaluated for high-speed and low-power memory applications. Herein, we investigated the influence of Al content in HfAlO thin films on the ferroelectric characteristics of HfAlO-based FTJs. Among HfAlO devices with different Hf/Al ratios (20:1, 34:1, and 50:1), the HfAlO device with Hf/Al ratio of 34:1 exhibited the highest remanent polarization and excellent memory characteristics and, thereby, the best ferroelectricity among the investigated devices. Furthermore, first-principal analyses verified that HfAlO thin films with Hf/Al ratio of 34:1 promoted the formation of the orthorhombic phase against the paraelectric phase as well as alumina impurities and, thus, enhanced the ferroelectricity of the device, providing theoretical support for supporting experimental results. The findings of this study provide insights for developing HfAlO-based FTJs for next-generation in-memory computing applications.

Obesity has been suggested as a risk factor for sarcopenia. Sarcopenic obesity (SO), as a new category of obesity, is a high-risk geriatric syndrome in elderly individuals. However, knowledge about the molecular pathomechanisms of SO is still sparse. In the present study, starting at 13 months, male Sprague-Dawley (SD) rats were fed a high-fat diet (HFD) and normal diet (ND) for 28 weeks to establish a rodent animal model of SO with an identical protocol, which was further assessed and verified as a successful SO model. Through RNA-seq analysis of gastrocnemius muscle in SO rats, we found that differentially expressed genes (DEGs) and alternative splicing events (ASEs) focused mainly on inflammatory, immune-response, skeletal muscle cell differentiation, fat cell differentiation and antigen processing and presentation. Furthermore, as the core regulation factor of skeletal muscle, the mef2c (myocyte enhancer Factor 2C) gene also has a significant alternative 3' splice site (A3SS) and down-regulated expression in HFD-induced SO. The alternative genes targeted by mef2c identified by GO analysis were enriched in transcript regulation of RNA polymerase II promoter. In conclusion, these explorative findings in aging high-fat-fed rats might serve as a firm starting point for understanding the pathway and mechanism of sarcopenic obesity., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Prostate cancer is one of the most lethal malignancies, and androgen deprivation therapy remains the mainstay of treatment for prostate cancer patients. Although androgen deprivation can initially come to remission, the disease often develops into castration-resistant prostate cancer (CRPC), which is still dependent on androgen receptor (AR) signaling and is related to a poor prognosis. Some success against CRPC has been achieved by drugs that target AR signaling, but secondary resistance uninterrupted emerges, and new therapies are urgently needed. In this study, we identified a potent small molecule compound, ZY-444, that suppressed PCa cells proliferation and metastasis, and inhibited tumor growth both in subcutaneous. Transcriptome sequencing analysis showed that TNFAIP3 was significantly elevated in prostate cancer cells after ZY-444 treatment. Further studies through overexpression of TNFAIP3 confirmed that TNFAIP3, as a direct target gene of ZY-444, contributes to the functions of ZY-444. In addition, we demonstrated the effects of TNFAIP3 on prostate cancer cell apoptosis, migration and proliferation to elucidate the mechanism of ZY-444. We found that TNFAIP3 inhibited the TNF signaling pathway, which could inhibit cell migration and proliferation and contribute to apoptosis. Overall, these findings highlighted TNFAIP3 as a tumor suppressor gene in the regulation of the progression and metastatic potential of prostate cancer and that targeting TNFAIP3 by ZY-444 might be a promising strategy for prostate cancer treatment., Competing Interests: None., (AJCR Copyright © 2023.)

Background: Few studies have focused on the incidence and correlation of social frailty (SF) with adverse health events in Southwest China. This study aims to explore the predictive value of SF for adverse health events., Methods: A 6-year prospective cohort study was employed, a total of 460 community-dwelling older adults aged 65 years and above were analyzed to provide a baseline in 2014. Participants completed two longitudinal follow-ups at 3 (2017, 426 participants involved) and 6 (2020, 359 participants involved) years later. A modified social frailty screening index was used in this study, and adverse health events such as physical frailty (PF) deterioration, disability, hospitalization, falls, and mortality were evaluated., Results: Among these participants in 2014, the median age was 71 years, 41.1% were male, and 71.1% were married or cohabiting, up to 112 (24.3%) of them were classified as SF. It was observed that aging (OR = 1.04, 95% CI = 1.00-1.07, P = 0.047) and having family members die in the past year (OR = 2.60, 95% CI = 0.93-7.25, P = 0.068) were risk factors of SF, whereas having a mate (OR = 0.40, 95% CI = 0.25-0.66, P = 0.000) and having family members to help with care (OR = 0.53, 95% CI = 0.26-1.11, P = 0.092) were protective factors of SF. The cross-sectional study demonstrated that SF was only significantly associated with disability (OR = 12.89, 95% CI = 2.67-62.13, P = 0.001) at wave 1. Baseline SF significantly explained the incidence of mortality at the 3-year (medium-term, OR = 4.89, 95% CI = 2.23-10.71, P = 0.000) and 6-year follow-ups (long-term, OR = 2.22, 95% CI = 1.15-4.28, P = 0.017)., Conclusion: SF prevalence was higher in the Chinese older population. Older adults with SF had a significantly increased incidence of mortality at the longitudinal follow-up. Consecutive comprehensive health management of SF (e.g., avoiding living alone and increasing social engagement) is urgently needed for the purposes of early prevention and multidimensional intervention in adverse health events, including disability and mortality., Competing Interests: KT was employed by Fosun Adgenvax Biopharmaceutical 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 © 2023 Sun, Tan, Tang, Liu, Zhu, Qin, Xia, Zhang, Chen, Nie and Wang.)

Background: Exosomes are nanosized membranous vesicles secreted by various types of cells, which facilitate intercellular communication by transporting bioactive compounds. Exosomes are abundant in biological fluids including semen, and their protein composition and the potential of seminal plasma exosomes (SPEs) as fertility biomarkers were elucidated in humans, however, little information is available regarding buffalo (Bubalus bubalis). Here, we examined protein correlation between spermatozoa, seminal plasma (SP), and SPEs, and we compared and analyzed protein differences between high-motility (H-motility) and low-motility (L-motility) SPEs in buffalo., Results: SPEs were concentrated and purified by ultracentrifugation combined with sucrose density gradient centrifugation, followed by verification using western blotting, nanoparticle tracking analysis, and transmission electron microscopy. Protein composition in spermatozoa, SP and SPEs, and protein difference in H- and L-motility SPEs were identified by LC-MS/MS proteomic analysis and were functionally analyzed through comprehensive bioinformatics. Many SPEs proteins originated from spermatozoa and SP, and nearly one third were also present in spermatozoa and SP. A series of proteins associated with reproductive processes including sperm capacitation, spermatid differentiation, fertilization, sperm-egg recognition, membrane fusion, and acrosome reaction were integrated in a functional network. Comparative proteomic analyses showed 119 down-regulated and 41 up-regulated proteins in L-motility SPEs, compared with H-motility SPEs. Gene Ontology (GO) enrichment of differentially expressed proteins (DEPs) showed that most differential proteins were located in sperm and vesicles, with activities of hydrolase and metalloproteinase, and were involved in sperm-egg recognition, fertilization, single fertilization, and sperm-zona pellucida binding processes, etc. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differential proteins were mainly involved in the PPRP signaling pathway, calcium signaling pathway, and cAMP signaling pathway, among others. Furthermore, 6 proteins associated with reproduction were validated by parallel reaction monitoring analysis., Conclusion: This study provides a comprehensive description of the seminal plasma exosome proteome and may be of use for further screening of biomarkers associated with male infertility., (© 2023. The Author(s).)

Polo like kinase 1 (PLK1) is a protein kinase involved in regulating the spindle assembly and cell cycle control in mammalian oocytes. SUMOylation, one way of post-translational modification, regulates oocyte meiosis by controlling several substrates. However, the relation between PLK1 and SUMOylation in oocytes is still unknown. In this study, we investigated that whether PLK1 was modified by SUMOylation in oocytes and its potential relationship with age-related meiotic abnormalities. We showed that PLK1 had colocalization and protein interaction with Small Ubiquitin-Like Modifier (SUMO)-1 and SUMO-2/3 in mouse oocytes, indicating that PLK1 could be modified by SUMO-1 and SUMO-2/3. Overexpression of PLK1 SUMOylation site mutants PLK1 K178R and PLK1 K191R caused the increase of the abnormal spindle rate of oocytes and the decline of the first polar body extrusion rate with the abnormal localization of PLK1, suggesting that the SUMOylation modification of PLK1 is essential for normal meiosis in oocytes. Compared with young mice, the expression of PLK1 protein increased and the expression of SUMO-1 and SUMO-2/3 protein decreased in the oocytes of aged mice, indicating that the SUMOylation of PLK1 might be related to the mouse aging. Therefore, our data suggested that PLK1 could be SUMOylated by SUMO-1 and SUMO-2/3 in mouse oocytes and SUMOylation of PLK1 regulated the meiosis progression of oocytes which was related with aging., (© 2022 Wiley Periodicals LLC.)

Background: Anatomic repair of anterior talofibular ligament (ATFL) is used to manage chronic lateral ankle instability (CLAI). However, the optimal suture configuration used to repair the ATFL is not yet determined. It remains unclear whether suture configuration affects clinical outcomes in such patients., Purpose: To compare the functional outcomes of all-inside arthroscopic ATFL repair using either a loop suture and or a free-edge suture configuration in CLAI patients., Study Design: Cohort study; Level of evidence, 3., Methods: This retrospective cohort study included 71 patients with CLAI who had undergone an all-inside arthroscopic ATFL repair procedure with either loop suture (n = 36) or free-edge suture (n = 35) from February 2016 to July 2018. Comparable pre-operatively, the Visual analogy score (VAS), American Orthopedic Foot and Ankle Society scoring system (AOFAS), Karlsson Ankle Functional Score (KAFS) scoring system, Anterior Talar Translation (ATT) and Active Joint Position Sense (AJPS) were used to evaluate postoperative ankle function., Results: There were no postoperative wound complications, implant reactions, or neurological or vascular injuries. Postoperative hospitalization, VAS, AOFAS, KAFS, AJPS and the time of return to sport were similar between the loop suture group and free-edge suture group. Requiring a longer procedure time, patients with loop suture configuration achieved better ATT., Conclusion: All-inside arthroscopic ATFL repair procedure for CLAI treatment provides better ATT and comparable functional outcomes when a loop suture configuration is used instead of a free-edge suture configuration. A statistical difference in ATT was observed. Given the relatively short follow-up, it is questionable whether this will have any clinical relevance., (© 2022. The Author(s).)

Objectives: There are few studies of metagenomic next-generation sequencing (mNGS) in immunocompromised patients assisted by veno-venous extracorporeal membrane oxygenation (vv-ECMO). The present study is aimed to investigate the pathogen-detected effect and clinical therapy value of mNGS technologies in immunocompromised patients assisted by vv-ECMO., Methods: Our study retrospectively enrolled 46 immunocompromised patients supported by vv-ECMO from Jan 2017 to June 2021 at the First Affiliated Hospital of Zhengzhou University, respectively. Patients were divided into the deterioration group (Group D) (n = 31) and improvement group (Group I) (n = 15) according to their outcomes. Baseline characteristics and etiological data of patients during hospitalization of 2 groups were compared. The pathogens detected by mNGS and antibiotic regimens guided by mNGS in immunocompromised patients assisted by vv-ECMO were analyzed., Results: Compared with Group I, the deterioration patients showed a higher percentage of chronic obstructive pulmonary disease (COPD) (32.3% vs. 6.7%, p < 0.01) and were significantly older (47.77 ± 16.72 years vs. 32 ± 15.05 years, p < 0.01). Within 48 h of being ECMO assisted, the consistency of the samples detected by traditional culture and mNGS at the same time was good (traditional culture vs. mNGS detection, the positive rate of bronchoalveolar lavage fluid (BALF) culture: 26.1% vs. 30.4%; the positive rate of blood sample culture: 12.2% vs. 12.2%, p > 0.05). However, mNGS detected far more pathogen species and strains than conventional culture (30 strains vs. 78 strains, p < 0.01); the most popular pathogen was Klebsiella pneumoniae . Parts of patients had their antibiotic treatment adjustments, and the improvement patients showed less usage of broad-spectrum antibiotics., Conclusions: mNGS may play a relatively important role in detecting mixed pathogens and personalized antibiotic treatment in immunocompromised patients assisted by vv-ECMO., 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 © 2022 Zhao, Ding, Zhao, Fu, Huang, Li, Sun, Kan, Li, Wang, Ma, Xu, Liu and Li.)

This study investigated a conceptual model by testing how parental romantic relationships influenced the depressive symptoms of grown-up children and whether the constructive communication patterns of grown-up children and romantic relationships played mediation effects within it. A total of 421 Chinese participants were enrolled in the study. The level of depressive symptoms, romantic relationship satisfaction and closeness, couple communication patterns, and parental romantic relationships were measured via self-report questionnaires. According to the results, the structural equation modeling analysis verified that the severity of participants' depressive symptoms was negatively associated with the parental romantic relationship and that the association was mediated by participants' constructive communication patterns and their own romantic relationships. Furthermore, compared with nondepressed participants, depressed participants were less satisfied with their parental romantic relationships, exhibited fewer constructive communication patterns, and were more distant and unsatisfied with current romantic relationships., 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 © 2022 Li, Zhang, Xiong, Sun, Qian and Sun.)

In order to imitate brain-inspired biological information processing systems, various neuromorphic computing devices have been proposed, most of which were prepared on rigid substrates and have energy consumption levels several orders of magnitude higher than those of biological synapses (∼10 fJ per spike). Herein, a new type of wearable organic ferroelectric artificial synapse is proposed, which has two modulation modes (optical and electrical modulation). Because of the high photosensitivity of organic semiconductors and the ultrafast polarization switching of ferroelectric materials, the synaptic device has an ultrafast operation speed of 30 ns and an ultralow power consumption of 0.0675 aJ per synaptic event. Under combined photoelectric modulation, the artificial synapse realizes associative learning. The proposed artificial synapse with ultralow power consumption demonstrates good synaptic plasticity under different bending strains. This provides new avenues for the construction of ultralow power artificial intelligence system and the development of future wearable devices.

Background: The anti-coagulation protocol of patients with hemorrhage risk primary disease who need extracorporeal membrane oxygenation (ECMO) supported is controversial. This study evaluated the feasibility of a new anti-coagulation strategy, that is heparin-free after 3000 IU heparin loaded in veno-venous ECMO (VV ECMO) supported acute respiratory failure patients with hemorrhage risk., Methods: A retrospective study was performed in a series of hemorrhage risk patients supported with VV ECMO at the First Affiliated Hospital of Zhengzhou University, between June 2012 to Sept 2020. A total of 70 patients received a low heparin bolus of 3000 units for cannulation but without subsequent, ongoing heparin administration. Patients were divided into survival (n = 25) and non-survival group (n = 45). Data of coagulation, hemolysis and membrane lung function were calculated and analyzed. The complications of patients were recorded. Finally, the binary Logistic regression was conducted., Results: The longest heparin-free time was 216 h, and the mean heparin-free time was 102 h. Compared with survivors, the non-survivors were showed higher baseline SOFA score and lower platelet counts in 0.5 h, 24 h, 48 h and 96 h after ECMO applied. However, there was no significant differences between survivors and non-survivors in ACT, APTT, INR, D-dimer, fibrinogen, LDH, blood flow rate, Δp and P post-ML O 2 (all p < 0.05) of all different time point. Moreover, only the baseline SOFA score was significantly associated with mortality (p < 0.001, OR(95%CI): 2.754 (1.486-5.103)) while the baseline levels of ACT, APTT, INR, platelet, D-dimer, fibrinogen and LDH have no association with mortality. The percentage of thrombosis complications was 54.3% (38/70) including 3 oxygenator changed but there was no significant difference of complications in survival and non-survival groups (p > 0.05)., Conclusions: The anticoagulation protocol that no heparin after a 3000 units heparin bolus in VV ECMO supported acute respiratory failure patients with hemorrhage risk is feasible., (© 2022. The Author(s).)

Primary hepatic stromal tumours are very rare and there are only sporadic reports in the literature. Due to the lack of specificity in their clinical manifestations and imaging features, these tumours are easily misdiagnosed. This current report presents a case of primary liver stromal tumour that was misdiagnosed as a liver cyst. The 72-year-old male patient was admitted to the hospital due to right upper abdomen fullness and discomfort for more than 2 weeks. Colour Doppler ultrasonography and enhanced computed tomography examinations revealed a cystic mass in the right lobe of the liver. The preoperative diagnosis was a liver cyst and the laparoscopic fenestration was performed. The pathological examination demonstrated that it was a primary hepatic stromal tumour. Gastroenteroscopy was performed postoperatively and no lesions were found in the gastrointestinal tract. Imatinib mesylate was given orally as the salvage therapy and a radical operation was planned at the patient's request. This current case serves as a reminder that clinicians should consider the possibility that it could be a primary hepatic stromal tumour rather than a hepatic cyst. A multidisciplinary team is necessary for the diagnosis and treatment of patients with a primary hepatic stromal tumour.

Research of artificial synapses is increasing in popularity with the development of bioelectronics and the appearance of wearable devices. Because the high-temperature treatment process of inorganic materials is not compatible with flexible substrates, organic ferroelectric materials that are easier to process have emerged as alternatives. An organic synaptic device based on P(VDF-TrFE) was prepared in this study. The device showed reliable P/E endurance over 10 4 cycles and a data storage retention capability at 80 °C over 10 4 s. Simultaneously, it possessed excellent synaptic functions, including short-term/ long-term synaptic plasticity and spike-timing-dependent plasticity. In addition, the ferroelectric performance of the device remained stable even under bending (7 mm bending radius) or after 500 bending cycles. This work shows that low-temperature processed organic ferroelectric materials can provide new ideas for the future development of wearable electronics and flexible artificial synapses., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2022 The Authors. Publishing Services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

With the development and application of artificial intelligence, there is an appeal to the exploitation of various sensors and memories. As the most important perception of human beings, vision occupies more than 80% of all the received information. Inspired by biological eyes, an artificial retina based on 2D Janus MoSSe was fabricated, which could simulate functions of visual perception with electronic/ion and optical comodulation. Furthermore, inspired by human brain, sensing, memory, and neuromorphic computing functions were integrated on one device for multifunctional intelligent electronics, which was beneficial for scalability and high efficiency. Through the formation of faradic electric double layer (EDL) at the metal-oxide/electrolyte interfaces could realize synaptic weight changes. On the basis of the optoelectronic performances, light adaptation of biological eyes, preprocessing, and recognition of handwritten digits were implemented successfully. This work may provide a strategy for the future integrated sensing-memory-processing device for optoelectronic artificial retina perception application.

Purpose/aim of the study: Posterior circulation stroke (PCS) accounts for 20% of ischemic stroke, and vertebrobasilar stenosis is an important cause of PCS. Notably, not all patients with artery stenosis progress to ischemic stroke, and one of the important reason is that collateral circulation construction plays important protection role in this process. Clinical presentation: Here, we present the case of a 71-year-old male who presented with lightheadedness and three episodes of loss of consciousness after bilateral subclavian artery stenting. Digital subtraction angiography (DSA) demonstrated severe stenosis of the left vertebral artery, and the bilateral subclavian artery was kept open. The patient was then given the left vertebral artery stenting in an effort to resolve the vascular stenosis. As expected, he achieved a complete remission after stenting. However, 6 months later the patient suffered from loss of consciousness again. Repeat DSA confirmed restenosis of the left vertebral artery, and revealed a collateral flow to the left vertebral artery which fed by external carotid collateral branches. Then DSA was performed after 12 months, and another collateral circulation involving thyrocervical trunk was also found supplying flow to the left vertebral artery. In this process, the frequency of loss of consciousness gradually decreased as the collateral circulation construction. Conclusion: Through this case, we observe the whole process of the collateral circulation construction. Moreover, this case serves as a testament to the variability and complexity of vertebrobasilar arteriopathies, suggesting promotion of collateral flow offers the opportunity for outcome improvement.

The performance of electrode material is correlated with the choice of electrolyte, however, how the solvation has significant impact on electrochemical behavior is underdeveloped. Herein, N-heteropentacenequinone (TAPQ) is investigated to reveal the solvation effect on the performance of sodium-ion batteries in different electrolyte environment. TAPQ cycled in diglyme-based electrolyte exhibits superior electrochemical performance, but experiences a rapid capacity fading in carbonate-based electrolyte. The function of solvation effect is mainly embodied in two aspects: one is the stabilization of anion intermediate via the compatibility of electrode and electrolyte, the other is the interfacial electrochemical characteristics influenced by solvation sheath structure. By revealing the failure mechanism, this work presents an avenue for better understanding electrochemical behavior and enhancing performance from the angle of solvation effect., (© 2021 Wiley-VCH GmbH.)

In-memory logic calculations and brain-inspired artificial synaptic neuromorphic computing are expected to solve the limitations of the traditional von Neumann computing architecture. The data processing efficiency of the traditional von Neumann architecture is inherently limited by its physically separated processing and storage units, and thus data transmission besides calculation leads to a limited calculation speed and additional high-power consumption. In addition, traditional digital logic calculations and analog calculations have greater limitations in conversion. Herein, we report a flexible two-terminal memristor based on SiCO:H, which is a porous low- k back-end complementary metal-oxide-semiconductor (CMOS)-compatible material. Due to its low operating voltage (200 mV) and fast response speed (100 ns), it could perform digital memory calculation and neuromorphic calculation simultaneously. The memristor could realize a transition from short-term to long-term plasticity in the process of enhancement and inhibition during neuromorphic calculation, with high biological reality. In digital logic calculations, IMP-based and MAGIC-based logic calculations were verified. In neuromorphic computing, an Ag ion-based conductive filament was introduced. The relationship between the temporal dynamics of the conductance evolution and the diffusive dynamics of the Ag active metal could be modulated by the external programming electric field strength. The synapses and neuron dynamics in biology were faithfully simulated, realizing a transition from short-term to long-term plasticity in the process of enhancement and inhibition, which has high compatibility and scalability, proposing a novel solution for the next generation of computer architectures.

Parvalbumin interneurons (PVIs) are affected in many psychiatric disorders including schizophrenia (SCZ), however the mechanism remains unclear. FXR1, a high confident risk gene for SCZ, is indispensable but its role in the brain is largely unknown. We show that deleting FXR1 from PVIs of medial prefrontal cortex (mPFC) leads to reduced PVI excitability, impaired mPFC gamma oscillation, and SCZ-like behaviors. PVI-specific translational profiling reveals that FXR1 regulates the expression of Cacna1h/Cav3.2 a T-type calcium channel implicated in autism and epilepsy. Inhibition of Cav3.2 in PVIs of mPFC phenocopies whereas elevation of Cav3.2 in PVIs of mPFC rescues behavioral deficits resulted from FXR1 deficiency. Stimulation of PVIs using a gamma oscillation-enhancing light flicker rescues behavioral abnormalities caused by FXR1 deficiency in PVIs. This work unveils the function of a newly identified SCZ risk gene in SCZ-relevant neurons and identifies a therapeutic target and a potential noninvasive treatment for psychiatric disorders., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: This study was performed to replicate the associations of genetic polymorphisms within nuclear factor-κB (NF-κB) signaling pathway genes with rheumatoid arthritis (RA), and to further examine genetic interactions in a Chinese population., Methods: A total of eleven single-nucleotide polymorphisms (SNPs) were genotyped in 594 RA patients and 604 healthy controls., Results: Genetic association analysis revealed that NFKBIE rs2233434, TNIP1 rs10036748 and BLK rs13277113 were significantly associated with RA, cyclic citrullinated peptide (CCP)-positive RA and rheumatoid factor (RF)-positive RA, and TNFAIP3 rs2230926 was significantly associated with CCP-positive RA. Significant additive interaction was observed between NFKB1 rs28362491 and IKBKE rs12142086 (RERI = 0.76, 95% CI 0.13-1.38; AP = 0.57, 95% CI 0.11-1.03), NFKBIE rs2233434 and BLK rs13277113 (RERI = 1.41, 95% CI 0.88-1.94; AP = 0.85, 95% CI 0.50-1.20), NFKBIL rs2071592 and TNIP1 rs10036748 (RERI = 0.59, 95% CI 0.17-1.02; AP = 0.46, 95% CI 0.05-0.87), UBE2L3 rs5754217 and TNFSF4 rs2205960 (RERI = 0.50, 95% CI 0.16-0.84; AP = 0.57, 95% CI 0.09-1.05). Significant multiplicative interaction was detected between BLK rs13277113 and UBE2L3 rs5754217 (p = 0.02), BLK rs13277113 and TNFSF4 rs2205960 (p = 0.03)., Conclusions: Our results lent further support to the role of NF-κB signaling pathway in the pathogenesis of RA from a genetic perspective., (Copyright © 2021 Elsevier B.V. All rights reserved.)