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Herein, a photocatalytic strategy for the synthesis of secondary alcohols by nucleophilic addition of an alkene with an aldehyde is described. This operationally simple methodology opens an approach for the synthesis of alcohols using commercially available reagents in moderate to excellent yields. Mechanistic studies indicate that the formation of the radical anion from alkene via single-electron transfer is the key step in this reaction.

Protein aggregation is a hallmark of numerous degenerative diseases, yet its underlying mechanisms remain poorly understood due to the challenges in identifying the composition and interaction networks of these aggregates. To address this issue, we developed TAggiXL, a novel method that combines fluorescence-traceable aggregate isolation with cross-linking proteomics, significantly enhancing the efficiency and precision of isolating protein aggregates. This method facilitates unbiased profiling of aggregated proteomes and their interactomes in live cells. The TAggiXL approach leverages advanced cross-linking proteomics, density gradient centrifugation, and fluorescence tracking to provide detailed characterization of protein aggregation under various stress conditions including HSP90 and proteasome inhibition. Using TAggiXL, we identified key components and interactions within the aggregates, particularly highlighting E3 ubiquitin ligase TRIM26, which plays a crucial role in aggregate formation and autophagic clearance under stress and pathogenic conditions. Moreover, TAggiXL revealed that HSPA1B functions as a central interaction hub within the aggregated proteome. It preferentially interacts with intrinsically disordered regions (IDRs) of aggregate components and demonstrates dynamic behavior within the aggregate. In summary, TAggiXL offers a powerful tool for dissecting the complex composition and interaction networks of protein aggregates, with a significant potential to advance our understanding of protein aggregation in degenerative diseases. It also holds promise for the development of future therapeutic interventions.

The increasing utilization of deep neural networks (DNNs) in safety-critical systems has raised concerns about their potential to exhibit undesirable behaviors. Consequently, DNN repair/patching arises in response to the times, and it aims to eliminate unexpected predictions generated by flawed DNNs. However, existing repair methods, both retraining- and fine-tuning-based, primarily focus on high-level abstract interpretations or inferences of state spaces, often neglecting the outputs of underlying neurons. As a result, present patching strategies become computationally prohibitive and own restricted application scope (often limited to DNNs with piecewise linear (PWL) activation functions), particularly for domain-wise repair problems (DRPs). To overcome these limitations, we introduce BIRDNN, a behavior-imitation based DNN repair framework that supports alternative retraining and fine-tuning repair paradigms for DRPs. BIRDNN employs a sampling technique to characterize DNN domain behaviors and rectifies incorrect predictions by imitating the expected behaviors of positive samples during the retraining-based repair process. As for the fine-tuning repair strategy, BIRDNN analyzes the behavior differences of neurons between positive and negative samples to pinpoint the most responsible neurons for erroneous behaviors, and then integrates particle swarm optimization algorithm (PSO) to fine-tune buggy DNNs locally. Furthermore, we have developed a prototype tool for BIRDNN and evaluated its performance on two widely used DRP benchmarks, the ACAS Xu DNN safety repair problem and the MNIST DNN robustness repair problem. The experiments demonstrate that BIRDNN features more excellent effectiveness, efficiency, and compatibility in repairing buggy DNNs comprehensively compared with state-of-the-art repair methods., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Micro-absorption spectroscopy is a useful tool for studying the biological characteristics of single cells. However, the weak spectral signal, due to low absorption caused by the tiny optical path length of the cell, makes the spectral data noisy and difficult to analyze. This paper describes a device for single-cell microspectroscopy measurement that integrates an optical fiber spectrometer and an image CCD within a microscopic system, allowing for the simultaneous acquisition of morphology information and the absorption spectrum of a single cell. The device utilizes an illumination source driven by modulated current sources instead of constant current sources and the corresponding spectral signal extraction method to reduce noise levels. It also features a transparent temperature-controlled sample chamber for regulating the sample's temperature, as the absorption of cells may change with temperature. Due to the unwanted baseline drift in the spectral signals, a method of analyzing the similarity degree between the measured spectrum and the standard spectrum is proposed to study the characteristic variation of cells. To verify the feasibility of this method, the device was used for the microscopic spectral measurement and analysis of single red blood cells. The results showed that the variation patterns of spectral parameters correspond to the cell's responses to changes in temperature and storage duration., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

The application of ketoconazole (KET) in ocular drug delivery is restricted by its poor aqueous solubility though its broad-spectrum antifungal activity. The aim of this study is to develop an ion-sensitive in situ gel (ISG) of KET to promote its ocular bioavailability in topical application. The solubility of KET in water was increased by complexation with hydroxypropyl-β-cyclodextrin (HPβCD), then KET-HPβCD inclusion complex (KET-IC) was fabricated into an ion-sensitive ISG triggered by sodium alginate (SA). The in vitro drug release and antifungal activities investigations demonstrated that the KET-IC-ISG formulation increased drug release and anti-fungal activities compared to pure KET. The ex vivo rabbit corneal permeation studied demonstrated higher permeability of KET-IC-ISG formulation ( P app of (6.34 ± 0.21) × 10 -4  cm/h) than pure KET ( P app of (3.09 ± 0.09) × 10 -4  cm/h). The cytotoxicity assay and the ocular irritation study in rabbits confirmed the KET-IC-ISG safety and well tolerance. The ocular pharmacokinetics of KET in rabbits was investigated and the results showed that the KET-IC-ISG increased its bioavailability in cornea by 47-fold. In conclusion, the KET-IC-ISG system promoted the precorneal retention, the ocular drug bioavailability and the developed formulation is a potential strategy to treat mycotic keratitis.

Background: Periorbital aging typically manifests with dermatochalasis and depression of the upper eyelid. While blepharoplasty is a popular choice for addressing upper eyelid skin laxity, it is not effective for treating sunken eyelids. This study introduces an innovative approach for periorbital rejuvenation by simultaneously addressing dermatochalasis and sunken upper eyelids in aging Asian women., Method: This study involved 45 patients with upper eyelid dermatochalasis accompanied by moderate to severe depression. Sub-brow blepharoplasty was performed in conjunction with upper eyelid granular fat grafting in the orbital septum for these patients. Preoperative measurements of the depth and volume of the upper eyelid depressions were taken, and surgical outcomes were assessed at 3 and 6 months postoperatively using the Global Aesthetic Improvement Scale (GAIS) score and the Antera 3D camera., Result: The average depth of the upper eyelid depression before surgery was 6.501 ± 1.473 mm, and the average volume was 0.579 ± 0.144 cm 3 . Significant improvements in both the depth and volume of the depressions were observed at 3 and 6 months after surgery compared to preoperative measurements. The GAIS scores were also improved and postoperative outcomes were deemed satisfactory., Conclusion: For patients with dermatochalasis accompanied by moderate to severe upper eyelid depression, standard blepharoplasty alone is insufficient to correct the sunken eyelid. This novel technique, which combines autologous granular fat injection into the orbital septum with blepharoplasty, effectively addresses periorbital aging, enhancing facial rejuvenation., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: Atherosclerosis is the basis of cardiovascular disease. Ferroptosis is a form of programmed cell death characterized by lipid peroxidation, which contributes to atherogenesis. The plant extract PNS (Panax notoginseng saponins), containing the main active ingredients of Panax notoginseng, exhibits anti-atherogenic properties. Herein, we determined whether PNS and its major components could attenuate atherosclerosis by suppressing ferroptosis and revealed the underlying mechanism(s)., Experimental Approach: The anti-atherogenic effects of PNS and their association with inhibition of ferroptosis was determined in apoE -/- mice. In vitro, the anti-ferroptotic effect and mechanism(s) of PNS components were demonstrated in the presence of ferroptosis inducers. Expression of ferroptosis markers and the ubiquitination of Keap1 were evaluated in USP2 -/- macrophages. Finally, the anti-atherogenic effect of USP2 knockout was determined by using USP2 -/- mice treated with high-fat diet (HFD) and AAV-PCSK9., Key Results: PNS inhibited ferroptosis and atherosclerosis in vivo. PNS suppressed ferroptosis and ferroptosis-aggravated foam cell formation and inflammation in vitro. Mechanistically, PNS and its components activated Nrf2 by antagonizing Keap1, which was attributed to the inhibition of USP2 expression. USP2 knockout antagonized ferroptosis and ferroptosis-aggravated foam cell formation and inflammation, thus mitigating atherosclerosis. USP2 knockout abolished inhibitory effects of PNS on foam cell formation and inflammation in vitro., Conclusion and Implications: PNS reduced USP2-mediated Keap1 de-ubiquitination and promoted Keap1 degradation, thereby activating Nrf2, improving iron metabolism and reducing lipid peroxidation, thus contributing to an anti-atherosclerotic outcome. Our study revealed the mechanism(s) underlying inhibition of ferroptosis and atherosclerosis by PNS., (© 2024 British Pharmacological Society.)

Previous studies have shown that at least six genera of the Cheilanthoideae, a subfamily of the fern family Pteridaceae, may not be monophyletic. In these non-monophyletic genera, the Old-World genus Paragymnopteris including approximately five species have long been controversial. In this study, with an extensive taxon sampling of Paragymnopteris, we assembled 19 complete plastomes of all recognized Paragymnopteris species, plastomes of Pellaea (3 species) and Argyrochosma (1 species), as well as transcriptomes from Paragymnopteris (6 species) and Argyrochosma (1 species). We conducted a comprehensive and systematic phylogenomic analysis focusing on the contentious relationships among the genus of Paragymnopteris through 9 plastid makers, the plastomes, mitochondria, nuclear ribosomal cistron genomes, and single-copy nuclear genes. Moreover, we further combined distribution, ploidy, and morphological features to investigate the evolution of Paragymnopteris. The backbone of Paragymnopteris was resolved consistently in the nuclear and plastid phylogenies. Our major results include: (1) Paragymnopteris is not monophyletic including two fully supported clades; (2) confirming that Paragymnopteris delavayi var. intermedia is a close relative of P. delavayi instead of P. marantae var. marantae; (3) the chromosome base number may not be a stable trait which has previously been used as an important character to divide Paragymnopteris into two groups; and (4) gene flow or introgression might be the main reason for the gene trees conflict of Paragymnopteris, but both gene flow and ILS might simultaneously and/or cumulatively act on the conflict of core pellaeids. The robust phylogeny of Paragymnopteris presented here will help us for the future studies of the arid to semi-arid ferns of Cheilanthoideae at the evolutionary, physiological, developmental, and omics-based levels., 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.)

Recent advances in single-cell proteomics enable the direct profiling of thousands of proteins from a single mammalian cell. However, due to the bottlenecks in detecting low-abundance secreted proteins and extracellular vesicle (EV) proteins (collectively referred to as the secretome) against a background of high-abundance proteins in serum-containing culture medium, the comprehensive investigation of the secretome at the single-cell level using nanoLC-MS/MS still remains challenging. Herein, we report a novel single-cell secretome profiling (SCSP) method by integrating the metabolic labeling of newly synthesized proteins, click chemistry-based enrichment, and in situ digestion of the labeled secretome in an alkyne-functionalized capillary micro-reactor, followed by nanoLC-MS/MS analysis. By this method, an average of 389 protein groups were quantified from the secretome of single HeLa cells (n=17), with a total of 752 protein groups confidently identified in the single-cell secretome, which is a significant increase compared to the previously reported targeted analysis limited to dozens of secreted proteins by antibody recognition. These results indicated that our developed SCSP method would provide a powerful tool to gain insights into secretion heterogeneity and intercellular communication at the single-cell level., (© 2024 Wiley-VCH GmbH.)

Metal-organic frameworks (MOFs) show potential application in many domains, in which photochromic MOFs (PMOFs) have received enormous attention. Researchers mainly utilize photoactive ligands to build PMOFs. Recently, the mixed electron donating and accepting ligands strategies have also been used to construct PMOFs driven by the electron transfer between nonphotochromic moieties. However, the potential interligand competition inhibits the formation of PMOFs. Therefore, the exploration of single-ligand-guided assembly is conductive for building PMOFs. Considering the existing electron accepting and donating role of pyridyl and carboxyl, the pyridinecarboxyate derived from the fusion of pyridyl and carboxyl units may serve as single ligand to yield PMOFs (Figure 1d). In this work, the coordination assembly of bipyridinedicarboxylate (2,2'-bipyridine-4,4'-dicarboxylic acid, H 2 bpdc; 1,10-phenanthroline-2,9-dicarboxylic acid, H 2 pda) and LaCl 3 generate two PMOFs, [La(bpdc)(H 2 O)Cl] (1) and [La(pda)(H 2 O) 2 Cl]⋅2H 2 O (2). Both complexes feature dinuclear lanthanum as building blocks with differences in the connecting number of likers, in which 1 has (4,8)-connected topology and 2 exhibits sql topology. Their structural differences result in the diversities of photoresponsive functionalities. Compared with reported PMOFs built from photoactive ligands and mixed ligands, this study provides new available categories of single ligand for generating PMOFs and tuning the structure and photoresponsive properties via ligand substitution and external photostimulus., (© 2024 Wiley-VCH GmbH.)

AlkB homolog 5 (ALKBH5) plays an important role in ischemia/reperfusion (I/R), cardiac hypertrophy and other cardiovascular diseases (CVDs). However, whether ALKBH5 regulates the inflammatory response by mediating M1/M2 macrophage conversion after myocardial infarction (MI) is unclear. In this study, we found that ALKBH5 protein expression was significantly downregulated in MI mice. To investigate the role of ALKBH5 in the inflammatory response after MI, we assessed the expression of interleukin-6 (Il-6), interleukin-1β (Il-1β), tumor necrosis factor-α (Tnf-α) and interferon-Ⅰ (Ifn-Ⅰ) by qRT‒PCR and found that ALKBH5 knockout improved cardiac function, reduced pro-inflammatory cytokine release and decreased cardiomyocyte apoptosis. In addition, the knockdown of ALKBH5 significantly inhibited the release of pro-inflammatory cytokines and the migration of RAW264.7 macrophages treated with lipopolysaccharide (LPS). Mechanistically, our results suggested that ALKBH5 potentially recognized the m 6 A binding site on interferon regulatory factor 3 (IRF3) and regulated the IRF3 expression to influence macrophage M1/M2 phenotypic transition and inflammatory cytokine release. In conclusion, our results indicated that ALKBH5 ablation inhibited inflammation by regulating the transcription of IRF3. This study provides new insights into the clinical management of the inflammatory response after MI., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Context: The association between magnesium status and metabolic syndrome (MetS) remains unclear., Objective: This study aimed to examine the relationship between kidney reabsorption-related magnesium depletion score (MDS) and MetS among US adults., Methods: We analyzed data from 15 565 adults participating in the National Health and Nutrition Examination Survey (NHANES) 2003 to 2018. MetS was defined according to the National Cholesterol Education Program's Adult Treatment Panel III report. The MDS is a scoring system developed to predict the status of magnesium deficiency that fully considers the pathophysiological factors influencing the kidneys' reabsorption capability. Weighted univariate and multivariable logistic regression were used to assess the association between MDS and MetS. Restricted cubic spline (RCS) analysis was conducted to characterize dose-response relationships. Stratified analyses by sociodemographic and lifestyle factors were also performed., Results: In both univariate and multivariable analyses, higher MDS was significantly associated with increased odds of MetS. Each unit increase in MDS was associated with approximately a 30% higher risk for MetS, even after adjusting for confounding factors (odds ratio 1.31; 95% CI, 1.17-1.45). RCS graphs depicted a linear dose-response relationship across the MDS range. This positive correlation remained consistent across various population subgroups and exhibited no significant interaction by age, sex, race, adiposity, smoking status, or alcohol consumption., Conclusion: Higher urinary magnesium loss as quantified by MDS may be an independent linear risk factor for MetS in US adults, irrespective of sociodemographic and behavioral factors. Optimizing magnesium nutritional status could potentially confer benefits to patients with MetS., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

A new fern species, Whittieriahengduanensis (Ophioglossaceae), from Sichuan, Xizang, and Yunnan, Southwest China (eastern Himalaya), is described and illustrated. This species is similar to W.engelmannii in the Americas in having a cylindrical rhizome and complex-reticulate venation. In addition, both species grow in open habitat on basic soil. However, the two species are distinguishable in root number per rhizome and the number of the larger areolae per trophophore. Our molecular study also supports that they are sister to each other but divergent at the molecular level. The discovery of W.hengduanensis shows that the genus is intercontinentally disjunct between the Himalaya and the Americas, a unique pattern not having been documented in the literature., Competing Interests: The authors have declared that no competing interests exist., (Zhen-Long Liang, Li-Bing Zhang.)

Vibrio alfacsensis is traditionally seen as an environmental symbiont within its genus, with no detailedly documented pathogenicity in marine aquaculture to date. This study delves into the largely unexplored pathogenic potential and emerging antibiotic resistance of V. alfacsensis. The VA-1 strain, isolated from recirculating aquaculture system (RAS) effluent of cultured turbot (Scophthalmus maximus), underwent comprehensive analysis including biochemical identification, antibiotic susceptibility testing and reinfection trials. The results confirmed VA-1's pathogenicity and significant multiple antibiotic resistance. VA-1 could induce systemic infection in turbot, with symptoms like kidney enlargement, exhibiting virulence comparable to known Vibrio pathogens, with an LD 50 around 2.36 × 10 6 CFU/fish. VA-1's remarkable resistance phenotype (14/22) suggested potential for genetic exchange and resistance factor acquisition in aquaculture environments. Phylogenetic analysis based on 16S rDNA sequences and whole-genome sequencing has firmly placed VA-1 within the V. alfacsensis clade, while genome-wide analysis highlights its similarity and diversity in relation to strains from across the globe. VA-1 contained numerous replicons, indicating the possibility for the spread of resistance and virulence genes. This study suggests V. alfacsensis may acquire and transfer pathogenic and resistant traits through horizontal gene transfer, a likelihood intensified by changing environmental and aquaculture conditions, highlighting the need for vigilant pathogen monitoring and new non-antibiotic treatments., 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: Naturalistic stimuli, such as videos, can elicit complex brain activations. However, the intricate nature of these stimuli makes it challenging to attribute specific brain functions to the resulting activations, particularly for higher-level processes such as social interactions., Objective: We hypothesized that activations in different layers of a convolutional neural network (VGG-16) would correspond to varying levels of brain activation, reflecting the brain's visual processing hierarchy. Additionally, we aimed to explore which brain regions would be linked to the deeper layers of the network., Methods: This study analyzed functional MRI data from participants watching a cartoon video. Using a pre-trained VGG-16 convolutional neural network, we mapped hierarchical features of the video to different levels of brain activation. Activation maps from various kernels and layers were extracted from video frames, and the time series of average activation patterns for each kernel were used in a voxel-wise model to examine brain responses., Results: Lower layers of the network were primarily associated with activations in lower visual regions, although some kernels also unexpectedly showed associations with the posterior cingulate cortex. Deeper layers were linked to more anterior and lateral regions of the visual cortex, as well as the supramarginal gyrus., Conclusions: This analysis demonstrated both the potential and limitations of using convolutional neural networks to connect video content with brain functions, providing valuable insights into how different brain regions respond to varying levels of visual processing., Competing Interests: One of the authors, Bharat B. Biswal, is also the associate editor of Psychoradiology. He was blinded from reviewing or making decisions on the manuscript., (© The Author(s) 2024. Published by Oxford University Press on behalf of West China School of Medicine/West China Hospital (WCSM/WCH) of Sichuan University.)

TGF-β stimulates CCN2 expression which in turn amplifies TGF-β signaling. This process promotes extracellular matrix production and accelerates the pathological progression of fibrotic diseases. Alternative splicing plays an important role in multiple disease development, while U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an essential factor in the early steps of pre-mRNA splicing. However, the molecular mechanism underlying abnormal CCN2 expression upon TGF-β stimulation remains unclear. This study elucidates that SIRT4 acts as a master regulator for CCN2 expression in response to TGF-β by modulating U2AF2-mediated alternative splicing. Analyses of renal biopsy specimens from patients with CKD and mouse fibrotic kidney tissues revealed marked nuclear accumulation of SIRT4. The tubulointerstitial fibrosis was alleviated by global deletion or tubular epithelial cell (TEC)-specific knockout of Sirt4 , and aggravated by adeno-associated virus-mediated SIRT4 overexpression in TECs. Furthermore, SIRT4 was found to translocate from the mitochondria to the cytoplasm through the BAX/BAK pore under TGF-β stimulation. In the cytoplasm, TGF-β activated the ERK pathway and induced the phosphorylation of SIRT4 at Ser36, which further promoted its interaction with importin α1 and subsequent nuclear translocation. In the nucleus, SIRT4 was found to deacetylate U2AF2 at K413, facilitating the splicing of CCN2 pre-mRNA to promote CCN2 protein expression. Importantly, exosomes containing anti-SIRT4 antibodies were found to effectively mitigate the UUO-induced kidney fibrosis in mice. Collectively, these findings indicated that SIRT4 plays a role in kidney fibrosis by regulating CCN2 expression via the pre-mRNA splicing., Competing Interests: GY, JX, XY, XL, YL, LL, LK, ZL, SY No competing interests declared, (© 2024, Yang, Xiang, Yang et al.)

Although immunotherapy has revolutionized cancer treatment, its efficacy is affected by multiple factors, particularly those derived from the complexity and heterogeneity of the tumor-immune microenvironment (TIME). Strategies that simultaneously and synergistically engage multiple immune cells in TIME remain highly desirable but challenging. Herein, we report a multimodal and programmable platform that enables the integration of multiple therapeutic modules into single agents for tumor-targeted co-engagement of multiple immune cells within TIME. We developed the triple orthogonal linker (T-Linker) technology to integrate various therapeutic small molecules and biomolecules as multimodal targeting chimeras (Multi-TACs). The EGFR-CD3-PDL1 Multi-TAC facilitated T-dendritic cell co-engagement to target solid tumors with excellent efficacy, as demonstrated in vitro, in several humanized mouse models and in patient-derived tumor models. Furthermore, Multi-TACs were constructed to coordinate T cells with other immune cell types. The highly modular and programmable feature of our Multi-TACs may find broad applications in immunotherapy and beyond., Competing Interests: Declaration of interests P.R.C., F.L., J. Lin, and H. Zhang are listed as inventors on a patent application (PCT/CN2021/130337) filed on this work through Peking University., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Upper eyelid tissue swelling is a common characteristic among Asian monolid individuals and is associated with a high incidence of complications following eyelid surgery. Currently, there is no precise definition for upper eyelid tissue swelling; thus, further research is required to elucidate the specific causes contributing to upper eyelid puffiness., Method: Between June 2023 and February 2024, we recruited 84 Asian monolid women categorized into groups based on the severity of upper eyelid tissue swelling: the puffy eyelid group and normal eyelid group. High-frequency ultrasound was employed to capture images of the upper eyelids and measure the thickness of various tissue layers. This study aimed to conduct a comparative analysis to identify the factors contributing to upper eyelid fullness, focusing on elucidating the underlying causes of this condition., Result: All volunteers underwent bilateral upper eyelid ultrasound imaging. Significant differences were observed in the thickness of subcutaneous fat, pre-tarsal fat, retro-orbicularis oculi fat (ROOF), and composite fat (ROOF and preaponeurotic fat) layer between the puffy and normal eyelid groups. However, no significant differences were found in skin thickness or orbicularis oculi muscle thickness. Additionally, no significant differences were observed in the thickness of various layers of the upper eyelid tissue between the left and right eyes in all participants., Conclusion: Thickening of the upper eyelid fat layer is a primary cause of upper eyelid puffiness. In upper blepharoplasty, targeted removal of preaponeurotic fat, ROOF, and pre-tarsal fat can achieve precise reduction to correct upper eyelid puffiness effectively., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Although the knee joint (KNJ) and temporomandibular joint (TMJ) all belong to the synovial joint, there are many differences in developmental origin, joint structure and articular cartilage type. Studies of joint development in embryos have been performed, mainly using poultry and rodents. However, KNJ and TMJ in poultry and rodents differ from those in humans in several ways. Very little work has been done on the embryonic development of KNJ and TMJ in large mammals. Several studies have shown that pigs are ideal animals for embryonic development research. Embryonic day 30 (E30), E35, E45, E55, E75, E90, Postnatal day 0 (P0) and Postnatal day 30 (P30) embryos/fetuses from the pigs were used for this study. The results showed that KNJ develops earlier than TMJ. Only one mesenchymal condensate of KNJ is formed on E30, while two mesenchymal condensates of TMJ are present on E35. All structures of KNJ and TMJ were formed on E45. The growth plate of KNJ begins to develop on E45 and becomes more pronounced from E55 to P30. From E75 to E90, more and more vascular-rich cartilage canals form in the cartilage regions of both joints. The cartilaginous canal of the TMJ divides the condyle into sections along the longitudinal axis of the condyle. This arrangement of cartilaginous canal was not found in the KNJ. The chondrification of KNJ precedes that of TMJ. Ossification of the knee condyle occurs gradually from the middle to the periphery, while that of the TMJ occurs gradually from the base of the mandibular condyle. In the KNJ, the ossification of the articular condyle is evident from P0 to P30, and the growth plate is completely formed on P30. In the TMJ, the cartilage layer of condyle becomes thinner from P0 to P30. There is no growth plate formation in TMJ during its entire development. There is no growth plate formation in the TMJ throughout its development. The condyle may be the developmental center of the TMJ. The chondrocytes and hypertrophic chondrocytes of the growth plate are densely arranged. The condylar chondrocytes of TMJ are scattered, while the hypertrophic chondrocytes are arranged. Embryonic development of KNJ and TMJ in pigs is an important bridge for translating the results of rodent studies to medical applications.

Adenosine-to-inosine (A-to-I) RNA editing plays essential roles in modulating normal development and homeostasis. This process is catalyzed by adenosine deaminase acting on RNA (ADAR) family proteins. The most well-understood biological processes modulated by A-to-I editing are innate immunity and neurological development, attributed to ADAR1 and ADAR2, respectively. A-to-I editing by ADAR1 is also critical in regulating hematopoiesis. This review will focus on the role of A-to-I RNA editing and ADAR enzymes, particularly ADAR1, during normal hematopoiesis in humans and mice. Furthermore, we will discuss Adar1 mouse models that have been developed to understand the contribution of ADAR1 to hematopoiesis and its role in innate immune pathways., Competing Interests: Conflict of Interest Disclosure The authors do not have any conflicts of interest to declare in relation to this work., (Copyright © 2024 International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)

Objective: This study examined the relationship between cystatin C (CysC) levels and all-cause, cardiovascular disease (CVD), and cancer mortality in US metabolic syndrome (MetS) patients., Methods: The 1999-2002 National Health and Nutrition Examination Survey (NHANES) prospective cohort research included 1980 MetS participants. To assess CysC levels and all-cause, CVD, and cancer mortality, fitted curves, Kaplan-Meier survival curves, Cox regression analysis, and receiver operating characteristic curves were performed., Results: During a mean follow-up of 15.3 ± 5.4 years, a total of 819 deaths occurred. The fitted and Kaplan-Meier survival curves revealed that greater CysC levels were linked to higher all-cause, CVD, and cancer mortality rates (P < .05). After adjusting for variables, CysC level was associated with all-cause, CVD, and cancer mortality at 1.63 (1.42-1.88), 1.53 (1.19-1.95), and 1.53 (1 ∼ 2.32), respectively (P < .05). Tertile models showed consistent results: high CysC Tertile participants showed higher risk of all-cause mortality (HR 1.87; 1.43-2.45), CVD mortality (HR 1.97, 1.15 ∼ 3.38), and cancer mortality (HR 1.72, 1.01 ∼ 2.91) compared to those in the lowest tertile (P < .05). Subgroup studies by sex and other characteristics confirmed the findings. CysC demonstrated the higher predictive efficacy across mortality outcomes, followed by eGFR, outperforming urea nitrogen, creatinine, uric acid, and C-reactive protein. CysC alone exhibited substantial predictive value for all-cause (AUC 0.773; P < .05) and CVD mortality (AUC 0.726; P < .05). Combining CysC with age enhanced predictive value for all-cause mortality to 0.861 and CVD mortality to 0.771 (P < .05)., Conclusion: MetS patients with elevated CysC levels have a higher risk of all-cause, CVD, and cancer death. CysC may predict MetS all-cause and CVD mortality., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Neurofeedback, when combined with cognitive reappraisal, offers promising potential for emotion regulation training. However, prior studies have predominantly relied on functional magnetic resonance imaging, which could impede its clinical feasibility. Furthermore, these studies have primarily focused on reducing negative emotions while overlooking the importance of enhancing positive emotions. In our current study, we developed a novel electroencephalogram (EEG) neurofeedback-guided cognitive reappraisal training protocol for emotion regulation. We recruited forty-two healthy subjects (20 females; 22.4 ± 2.2 years old) who were randomly assigned to either the neurofeedback group or the control group. We evaluated the efficacy of this newly proposed neurofeedback training approach in regulating emotions evoked by pictures with different valence levels (low positive and high negative). Initially, we trained an EEG-based emotion decoding model for each individual using offline data. During the training process, we calculated the subjects' real-time self-regulation performance based on the decoded emotional states and fed it back to the subjects as feedback signals. Our results indicate that the proposed decoded EEG neurofeedback-guided cognitive reappraisal training protocol significantly enhanced emotion regulation performance for stimuli with low positive valence. Additionally, wavelet energy and differential entropy features in the high-frequency band played a crucial role in emotion classification and were associated with neural plasticity changes induced by emotion regulation. These findings validate the beneficial effects of the proposed EEG neurofeedback protocol and offer insights into the neural mechanisms underlying its training effects. This novel decoded neurofeedback training protocol presents a promising cost-effective and non-invasive treatment technique for emotion-related mental disorders., Competing Interests: Conflict of interestThe authors have no competing interests to declare that are relevant to the content of this article., (© The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Emotion recognition is crucial for human-computer interaction, and electroencephalography (EEG) stands out as a valuable tool for capturing and reflecting human emotions. In this study, we propose a hierarchical hybrid model called Mixed Attention-based Convolution and Transformer Network (MACTN). This model is designed to collectively capture both local and global temporal information and is inspired by insights from neuroscientific research on the temporal dynamics of emotions. First, we introduce depth-wise temporal convolution and separable convolution to extract local temporal features. Then, a self-attention-based transformer is used to integrate the sparse global emotional features. Besides, channel attention mechanism is designed to identify the most task-relevant channels, facilitating the capture of relationships between different channels and emotional states. Extensive experiments are conducted on three public datasets under both offline and online evaluation modes. In the multi-class cross-subject online evaluation using the THU-EP dataset, MACTN demonstrates an approximate 8% enhancement in 9-class emotion recognition accuracy in comparison to state-of-the-art methods. In the multi-class cross-subject offline evaluation using the DEAP and SEED datasets, a comparable performance is achieved solely based on the raw EEG signals, without the need for prior knowledge or transfer learning during the feature extraction and learning process. Furthermore, ablation studies have shown that integrating self-attention and channel-attention mechanisms improves classification performance. This method won the Emotional BCI Competition's final championship in the World Robot Contest. The source code is available at https://github.com/ThreePoundUniverse/MACTN., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Muscle atrophy can cause muscle dysfunction and weakness. Krüppel-like factor 13 (KLF13), a central regulator of cellular energy metabolism, is highly expressed in skeletal muscles and implicated in the pathogenesis of several diseases. This study investigated the role of KLF13 in muscle atrophy, which could be a novel therapeutic target., Methods: The effects of gene knockdown and pharmacological targeting of KLF13 on skeletal muscle atrophy were investigated using cell-based and animal models. Clofoctol, an antibiotic and KLF13 agonist, was also investigated as a candidate for repurposing. The mechanisms related to skeletal muscle atrophy were assessed by measuring the expression levels and activation statuses of key regulatory pathways and validated using gene knockdown and RNA sequencing., Results: In a dexamethasone-induced muscle atrophy mouse model, the KLF13 knockout group had decreased muscle strength (N) (1.77 ± 0.10 vs. 1.48 ± 0.16, P < 0.01), muscle weight (%) [gastrocnemius (Gas): 76.0 ± 5.69 vs. 60.7 ± 7.23, P < 0.001; tibialis anterior (TA): 75.8 ± 6.21 vs. 67.5 ± 5.01, P < 0.05], and exhaustive running distance (m) (495.5 ± 64.8 vs. 315.5 ± 60.9, P < 0.05) compared with the control group. KLF13 overexpression preserved muscle mass (Gas: 100 ± 6.38 vs. 120 ± 14.4, P < 0.01) and the exhaustive running distance (423.8 ± 59.04 vs. 530.2 ± 77.45, P < 0.05) in an in vivo diabetes-induced skeletal muscle atrophy model. Clofoctol treatment protected against dexamethasone-induced muscle atrophy. Myotubes treated with dexamethasone, an atrophy-inducing glucocorticoid, were aggravated by KLF13 knockout, but anti-atrophic effects were achieved by inducing KLF13 overexpression. We performed a transcriptome analysis and luciferase reporter assays to further explore this mechanism, finding that delta-like 4 (Dll4) was a novel target gene of KLF13. The KLF13 transcript repressed Dll4, inhibiting the Dll4-Notch2 axis and preventing muscle atrophy. Dexamethasone inhibited KLF13 expression by inhibiting myogenic differentiation 1 (i.e., MYOD1)-mediated KLF13 transcriptional activation and promoting F-Box and WD repeat domain containing 7 (i.e., FBXW7)-mediated KLF13 ubiquitination., Conclusions: This study sheds new light on the mechanisms underlying skeletal muscle atrophy and potential drug targets. KLF13 regulates muscle atrophy and is a potential therapeutic target. Clofoctol is an attractive compound for repurposing studies to treat skeletal muscle atrophy., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Response latency is a critical parameter in studying human behavior, representing the time interval between the onset of stimulus and the response. However, different time between devices can introduce errors. Serial port synchronization signal can mitigate this, but limited information is available regarding their accuracy. Optical signals offer another option, but the difference in the positioning of optical signals and visual stimuli can introduce errors, and there have been limited reports of error reduction. This study aims to investigate methods for reducing the time errors. We used the Psychtoolbox to generate visual stimuli and serial port synchronization signals to explore their accuracy. Subsequently, we proposed a calibration formula to minimize the error between optical signals and visual stimuli. The findings are as follows: Firstly, the serial port synchronization signal presenting precedes visual stimulation, with a smaller lead time observed at higher refresh rates. Secondly, the lead time increases as the stimulus position deviates to the right and downwards. In Linux and IOPort(), serial port synchronization signals exhibited greater accuracy. Considering the poor accuracy and the multiple influencing factors associated with serial port synchronization signals, it is recommended to use optical signals to complete time synchronization. The results indicate that under the darkening process, the time error is - 0.23 ~ 0.08 ms (mean). This calibration formula can help measure the response latency accurately. This study provides valuable insights for optimizing experimental design and improving the accuracy of response latency. Although it only involves visual stimuli, the methods and results of this study can still serve as a reference., (© 2024. The Psychonomic Society, Inc.)

Aim: To synthesize available evidence about core competencies for nurses engaged in palliative care., Design: A scoping review conducted according to the framework from Joanna Briggs Institute., Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist was adopted to report this scoping review. The PubMed, Web of Science, Embase, ScienceDriect, CNKI, WangFang, VIP and Sinomed databases were used to systematically search for published studies from their inception to December 2023. Two researchers independently screened and selected relevant studies and performed the data charting., Results: Twenty-six studies were included in this scoping review. Among these, 14 studies identified core competency assessment instruments among nurses engaged in palliative care, with the Palliative Care Core Competence Questionnaire was used most frequently; 13 studies investigated the status of core competencies of nurses engaged in palliative care, the majority of included studies indicated that nurse's core competencies were at moderate levels; 11 studies explored the factors influencing the core competencies of the nurses engaged in palliative care, which were classified as sociodemographic-related factors, palliative care education-related factors, death attitude, palliative care practice-related experience and others., Conclusion: This scoping review offers a comprehensive overview of the current landscape of core competencies among nurses in palliative care. Findings suggested that the clinical nursing leaders need to develop tailored strategies and interventions to address specific factors and promote the continuous development of nurses' competencies in palliative care., Relevance to Clinical Practice: Core competency assessment instruments equip nurses and healthcare organizations with a range of validated tools for evaluating their proficiency in palliative care. Targeted core competency enhancement programmes need to be developed to foster a nursing workforce better equipped to improve the quality of life of end-of-life patients and their families., Patient or Public Contribution: No patient or public contribution., (© 2024 John Wiley & Sons Ltd.)

Unlocking the intricacies of protein structures and interactions within the dynamic landscape of subcellular organelles presents a significant challenge. To address this, we introduce SPACX, a method for spatially resolved protein complex profiling via biocompatible chemical cross(x)-linking with subcellular isolation, designed to monitor protein conformation, interactions, and translocation in living cells. By rapidly capturing protein complexes in their native physiological state and efficiently enriching cross-linked peptides, SPACX allows comprehensive analysis of the protein interactome within living cells. Leveraging structure refinement with cross-linking restraints, we identify subcellular-specific conformation heterogeneity of PTEN, revealing dynamic differences in its dual specificity domains between the nucleus and cytoplasm. Furthermore, by discerning conformational disparities, we identify 83 cytoplasm-exclusive and 109 nucleus-exclusive PTEN-interacting proteins, each associated with distinct biological functions. Upon induction of ubiquitin-proteasome system stress, we observe dynamic alterations in PTEN assembly and its interacting partners during translocation. These changes, including the identification of components and interaction sites, are characterized using the SPACX approach. Notably, SPACX enables identification of unique interacting proteins specific to PTEN isoforms, including PTEN and PTEN-Long, through the determination of sequence-specific cross-linking interfaces. These findings underscore the potential of SPACX to elucidate the functional diversity of proteins within distinct subcellular sociology., (© 2024. The Author(s).)

Introduction: Older adults with multimorbidity are at high risk of cognitive impairment development. There is a lack of research on the associations between different multimorbidity measures and cognitive function among older Chinese adults living in the community., Methods: We used the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2018 and included data on dementia-free participants aged ≥65 years. Multimorbidity measures included condition counts, multimorbidity patterns, and trajectories. The association of multimorbidity measures with cognitive function was examined by generalized estimating equation and linear and logistic regression models., Results: Among 14,093 participants at baseline, 43.2% had multimorbidity. Multimorbidity patterns were grouped into cancer-inflammatory, cardiometabolic, and sensory patterns. Multimorbidity trajectories were classified as "onset-condition," "newly developing," and "severe condition." The Mini-Mental State Examination scores were significantly lower for participants with more chronic conditions, with cancer-inflammatory/cardiometabolic/sensory patterns, and with developing multimorbidity trajectories., Discussion: Condition counts, sensory pattern, cardiometabolic pattern, cancer-inflammatory pattern, and multimorbidity developmental trajectories were prospectively associated with cognitive function., Highlights: Elderly individuals with a higher number of chronic conditions were associated with lower MMSE scores in the Chinese Longitudinal Healthy Longevity Survey data. MMSE scores were significantly lower for participants with specific multimorbidity patterns. Individuals with developing trajectories of multimorbidity were associated with lower MMSE scores and a higher risk of mild cognitive impairment., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Bacteria can be utilized for cancer therapy owing to their preferential colonization at tumor sites. However, unmodified non-pathogenic bacteria carry potential risks due to their non-specific targeting effects, and their anti-tumor activity is limited when used as monotherapy. In this study, a biohybrid-engineered bacterial system comprising non-pathogenic MG1655 bacteria modified with CDH17 nanobodies on their surface and conjugated with photosensitizer croconium (CR) molecules is developed. The resultant biohybrid bacteria can efficiently home to CDH17-positive tumors, including gastric, pancreatic, and colorectal cancers, and significantly suppress tumor growth upon irradiation. More importantly, biohybrid bacteria-mediated photothermal therapy (PTT) induced abundant macrophage infiltration in a syngeneic murine colorectal model. Further, that the STING pathway is activated in tumor macrophages by the released bacterial nucleic acid after PTT is revealed, leading to the production of type I interferons. The addition of CD47 nanobody but not PD-1 antibody to the PTT regimen can eradicate the tumors and extend survival. This results indicate that bacteria endowed with tumor-specific selectivity and coupled with photothermal payloads can serve as an innovative strategy for low-immunogenicity cancers. This strategy can potentially reprogram the tumor microenvironment by inducing macrophage infiltration and enhancing the efficacy of immunotherapy targeting macrophages., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Corneal neovascularization (CNV) is a common eye disease that leads to blindness. New treatment strategies are urgently needed due to the limitations of current treatment methods., Methods: We report the synthesis of peptide Nap-FFEEPCAIWF ( Comp.3 ) via chemical conjugation of Nap-FFEE ( Comp.2 ) to antiangiogenic peptide PCAIWF ( Comp.1 ) . Comp.3 self-assembled into a hydrogel ( gel of 3 ) composed of nanofibers, which enhanced the antiangiogenic function of the epitope., Results: We developed a novel peptide with an amphiphilic framework, Comp.3 , which could self-assemble into a supramolecular hydrogel with a well-ordered nanofiber structure. The nanofibers exhibited good biocompatibility with corneal epithelial cells, presenting a promising strategy to enhance the efficacy of free peptide-based drugs in the treatment of ocular vascular diseases, such as CNV and other angiogenesis-related diseases., Conclusion: Nap-FFEEPCAIWF nanofibers provide an alternative approach to enhancing the therapeutic efficiency of free peptide-based drugs against ocular vascular diseases., Competing Interests: The authors declare that there are no conflicts of interest in this work., (© 2024 Pu et al.)

Marine microbes drive pivotal transformations in planetary-scale elemental cycles and have crucial impacts on global biogeochemical processes. Metaproteomics is a powerful tool for assessing the metabolic diversity and function of marine microbes. However, hundreds of liters of seawater are required for normal metaproteomic analysis due to the sparsity of microbial populations in seawater, which poses a substantial challenge to the widespread application of marine metaproteomics, particularly for deep seawater. Herein, a sensitive marine metaproteomics workflow, named sensitive marine metaproteome analysis (SMMP), was developed by integrating polycarbonate filter-assisted microbial enrichment, solid-phase alkylation-based anti-interference sample preparation, and narrow-bore nanoLC column for trace peptide separation and characterization. The method provided more than 8500 proteins from 1 L of bathypelagic seawater samples, which covered diverse microorganisms and crucial functions, e.g., the detection of key enzymes associated with the Wood-Ljungdahl pathway. Then, we applied SMMP to investigate vertical variations in the metabolic expression patterns of marine microorganisms from the euphotic zone to the bathypelagic zone. Methane oxidation and carbon monoxide (CO) oxidation were active processes, especially in the bathypelagic zone, which provided a remarkable energy supply for the growth and proliferation of heterotrophic microorganisms. In addition, marker protein profiles detected related to ammonia transport, ammonia oxidation, and carbon fixation highlighted that Thaumarchaeota played a critical role in primary production based on the coupled carbon-nitrogen process, contributing to the storage of carbon and nitrogen in the bathypelagic regions. SMMP has low microbial input requirements and yields in-depth metaproteome analysis, making it a prospective approach for comprehensive marine metaproteomic investigations.

Platensilin, platensimycin, and platencin are potent inhibitors of β-ketoacyl-acyl carrier protein synthase (FabF) in the bacterial and mammalian fatty acid synthesis system, presenting promising drug leads for both antibacterial and antidiabetic therapies. Herein, a bioinspired skeleton reconstruction approach is reported, which enables the unified synthesis of these three natural FabF inhibitors and their skeletally diverse analogs, all stemming from a common ent -pimarane core. The synthesis features a diastereoselective biocatalytic reduction and an intermolecular Diels-Alder reaction to prepare the common ent -pimarane core. From this intermediate, stereoselective Mn-catalyzed hydrogen atom-transfer hydrogenation and subsequent Cu-catalyzed carbenoid C-H insertion afford platensilin. Furthermore, the intramolecular Diels-Alder reaction succeeded by regioselective ring opening of the newly formed cyclopropane enables the construction of the bicyclo[3.2.1]-octane and bicyclo[2.2.2]-octane ring systems of platensimycin and platencin, respectively. This skeletal reconstruction approach of the ent -pimarane core facilitates the preparation of analogs bearing different polycyclic scaffolds. Among these analogs, the previously unexplored cyclopropyl analog 47 exhibits improved antibacterial activity (MIC 80 = 0.0625 μg/mL) against S. aureus compared to platensimycin.

Cisplatin (DDP) is commonly used in the treatment of non-small cell lung cancer (NSCLC), including lung adenocarcinoma (LUAD), and the primary cause for its clinical inefficacy is chemoresistance. Here, we aimed to investigate a novel mechanism of chemoresistance in LUAD cells, focusing on the calcium-sensing receptor (CaSR). In this study, high CaSR expression was detected in DDP-resistant LUAD cells, and elevated CaSR expression is strongly correlated with poor prognosis in LUAD patients receiving chemotherapy. LUAD cells with high CaSR expression exhibited decreased sensitivity to cisplatin, and the growth of DDP-resistant LUAD cells was inhibited by cisplatin treatment in combination with CaSR suppression, accompanied by changes in BRCA1 and cyclin B1 protein expression both in vitro and in vivo . Additionally, an interaction between CaSR and KIF11 was identified. Importantly, suppressing KIF11 resulted in decreased protein levels of BRCA1 and cyclin B1, enhancing the sensitivity of DDP-resistant LUAD cells to cisplatin with no obvious decrease in CaSR. Here, our findings established the critical role of CaSR in promoting cisplatin resistance in LUAD cells by modulating cyclin B1 and BRCA1 and identified KIF11 as a mediator, highlighting the potential therapeutic value of targeting CaSR to overcome chemoresistance in LUAD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objectives: This study aimed to summarize the existing literature on risk factors for arrhythmias after chemotherapy in cancer patients. To provide reliable evidence for treating arrhythmias after chemotherapy in oncology patients by assessing multiple biasing factors in the literature and quantifying the risk factors., Methods: The risk factors for arrhythmia following tumor chemotherapy were systematically collected from various reputable databases, including PubMed, Cochrane Library, MEDLINE, EMBASE, and multiple Chinese databases, covering the period from inception to May 2023. Two independent reviewers performed rigorous article screening, data extraction, and assessment of research quality. Data analysis was conducted using Review Manager 5.4 software, ensuring a standardized and robust approach to evaluate the gathered evidence., Results: The analysis of chemotherapy-induced arrhythmias included 16 articles, encompassing 14,785 cancer patients. Among the patients, 3295 belonged to the arrhythmia group, while 11,490 were in the non-arrhythmia group. These studies identified 12 significant risk factors associated with arrhythmias following chemotherapy in cancer patients. The findings of the analysis are as follows., General Patient Characteristics: The incidence of post-chemotherapy arrhythmias was 14.33 times higher in oncology patients aged ≥60 years compared to patients <60 years of age [OR = 14.33, 95%CI (8.51, 24.13), P ＜0.00001]. Patients with a smoking history exhibited a 1.67-fold higher risk of arrhythmia after chemotherapy [OR = 1.67, 95%CI (1.24, 2.25), P  = 0.0007]. However, there was no significant correlation between gender and body mass index (BMI) with arrhythmia after chemotherapy in oncology patients ( P  = 0.52; P  = 0.19)., Disease-Related Factors: Patients with a history of hypertension, diabetes, and cardiovascular disease had a 1.93-fold, 1.30-fold, and 1.76-fold increased risk of arrhythmia after chemotherapy, respectively [OR = 1.93, 95%CI (1.66, 2.24), P ＜0.00001; OR = 1.30, 95%CI (1.10, 2.52), P  = 0.002; OR = 1.76, 95%CI (1.51, 2.05), P ＜0.00001]. Additionally, the incidence of arrhythmia increased 1.97 times in patients with electrolyte and acid-base balance disorders following chemotherapy [OR = 1.97, 95%CI (1.41, 2.76), P ＜0.00001]., Chemotherapy-Related Factors: Seven articles examined the association between chemotherapy drugs and post-chemotherapy arrhythmias. The results indicated that oncology patients were 3.03 times more likely to develop arrhythmias with chemotherapy drugs compared to non-chemotherapy drugs [OR = 3.03, 95%CI (2.59, 3.54), P ＜0.00001]. Notably, anthracyclines and fluorouracil chemotherapy demonstrated a 2.98-fold and 3.35-fold increased risk of arrhythmia after chemotherapy, respectively [OR = 2.98, 95%CI (2.51, 3.03), P ＜0.00001; OR = 3.35, 95%CI (2.20, 5.10), P ＜0.00001]. The risk of arrhythmia after chemotherapy was 1.72 times higher in patients with chemotherapy cycles longer than 4 weeks than those with cycles shorter than 4 weeks [OR = 1.72, 95%CI (1.30, 2.28), P  = 0.0001]., Conclusion: The occurrence of arrhythmia after chemotherapy in cancer patients was significantly associated with the patient's age, history of smoking, history of hypertension, history of diabetes, history of cardiovascular disease, chemotherapy drug use, and cycle. However, further high-quality evidence is needed to support these results., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease that has been prevalent since December 2019. Chinese medicine (CM) has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention, improvement of clinical symptoms, and control of disease progression. This review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel coronavirus. On the basis of sorting out experimental methods in vivo and in vitro, the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related complications. The aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19, and to provide a basis for the research and scientific, standardized treatment of COVID-19 with CM., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

The intricate relationship between prestimulus alpha oscillations and visual contrast detection variability has been the focus of numerous studies. However, the causal impact of prestimulus alpha traveling waves on visual contrast detection remains largely unexplored. In our research, we sought to discern the causal link between prestimulus alpha traveling waves and visual contrast detection across different levels of mental fatigue. Using electroencephalography alongside a visual detection task with 30 healthy adults (13 females; 17 males), we identified a robust negative correlation between prestimulus alpha forward traveling waves (FTWs) and visual contrast threshold (VCT). Inspired by this correlation, we utilized 45/-45° phase-shifted transcranial alternating current stimulation (tACS) in a sham-controlled, double-blind, within-subject experiment with 33 healthy adults (23 females; 10 males) to directly modulate these alpha traveling waves. After the application of 45° phase-shifted tACS, we observed a substantial decrease in FTW and an increase in backward traveling waves, along with a concurrent increase in VCT, compared with the sham condition. These changes were particularly pronounced under a low fatigue state. The findings of state-dependent tACS effects reveal the potential causal role of prestimulus alpha traveling waves in visual contrast detection. Moreover, our study highlights the potential of 45/-45° phase-shifted tACS in cognitive modulation and therapeutic applications., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Protein phosphorylation is one of the most common and important post-translational modifications that regulates almost all life processes. In particular, protein phosphorylation regulates the development of major diseases such as tumors, neurodegenerative diseases, and diabetes. For example, excessive phosphorylation of Tau protein can cause neurofibrillary tangles, leading to Alzheimer's disease. Therefore, large-scale methods for identifying protein phosphorylation must be developed. Rapid developmentin efficient enrichment methods and biological mass spectrometry technologies have enabled the large-scale identification of low-abundance protein O -phosphorylation modifications in, allowing for a more thorough study of their biological functions. The N -phosphorylation modifications that occur on the side-chain amino groups of histidine, arginine, and lysine have recently received increased attention. For example, the biological function of histidine phosphorylation in prokaryotes has been well studied; this type of modification regulates signal transduction and sugar metabolism. Two mammalian pHis kinases (NME1 and NME2) and three pHis phosphatases (PHPT1, LHPP, and PGAM5) have been successfully identified using various biological methods. N -Phosphorylation is involved in multiple biological processes, and its functions cannot be ignored. However, N -phosphorylation is unstable under acidic and thermal conditions owing to the poor chemical stability of the P-N bond. Unfortunately, the current O -phosphorylation enrichment method, which relies on acidic conditions, is unsuitable for N -phosphorylation enrichment, resulting in a serious lag in the large-scale identification of protein N -phosphorylation. The lack of enrichment methods has also seriously hindered studies on the biological functions of N -phosphorylation. Therefore, the development of efficient enrichment methods that target protein N -phosphorylation is an urgent undertaking. Research on N -phosphorylation proteome enrichment methods is limited, hindering functional research. Thus, summarizing such methods is necessary to promote further functional research. This article introduces the structural characteristics and reported biological functions of protein N -phosphorylation, reviews the protein N -phosphorylation modification enrichment methods developed over the past two decades, and analyzes the advantages and disadvantages of each method. In this study, both antibody-based and nonantibody-dependent methods are described in detail. Owing to the stability of the molecular structure of histidine, the antibody method is currently limited to histidine phosphorylation enrichment research. Future studies will focus on the development of new enrichment ligands. Moreover, research on ligands will promote studies on other nonconventional phosphorylation targets, such as two acyl-phosphates (pAsp, pGlu) and S -phosphate (pCys). In summary, this review provides a detailed analysis of the history and development directions of N -phosphorylation enrichment methods.

Mechanical stress stands as a fundamental factor in the intricate processes governing the growth, development, morphological shaping, and maintenance of skeletal mass. The profound influence of stress in shaping the skeletal framework prompts the assertion that stress essentially births the skeleton. Despite this acknowledgment, the mechanisms by which the skeleton perceives and responds to mechanical stress remain enigmatic. In this comprehensive review, our scrutiny focuses on the structural composition and characteristics of sclerotin, leading us to posit that it serves as the primary structure within the skeleton responsible for bearing and perceiving mechanical stress. Furthermore, we propose that osteocytes within the sclerotin emerge as the principal mechanical-sensitive cells, finely attuned to perceive mechanical stress. And a detailed analysis was conducted on the possible transmission pathways of mechanical stress from the extracellular matrix to the nucleus., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bo Wei reports financial support was provided by Zhanjiang Science and Technology Bureau. Chengshuo Huang reports financial support was provided by Zhanjiang Science and Technology Bureau. Bo Wei reports financial support was provided by Affiliated Hospital of Guangdong Medical University. If there are other authors, they 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background & Aims: Knee osteoarthritis (KOA) is a progressive degenerative disease of chronic nature. The mainstay of surgical management for KOA would be total knee arthroplasty. Joint preserving options like High Tibial Osteotomy (HTO) and Proximal Fibular Osteotomy (PFO) have been offered as an inexpensive option by knee preservation surgeons. Current literature on PFO outcomes lack of clarity for specific indications for offering PFO based on degree of severity of KOA. Therefore, this systematic review aims to critically evaluate clinical and radiological outcomes of PFO stratified by severity of KOA., Methods: PubMed, Scopus, CINAHL and Google Scholar databases were searched. Eligible studies included those published up till August 2023, with 271 studies obtained. After duplicate removal, title-abstract screening, and a full text screen based on inclusion and exclusion criteria, 11 papers were included. 46 papers were further identified from snowballing of 7 existing systematic reviews, with 2 additional papers subsequently included., Results: 13 included articles analysed 788 knees. Our study found that indications based on KL grading of KOA do not seem to differ in terms of post-operative clinical outcomes (VAS score) and radiological measures also found that hip knee alignment was improved regardless of KL grading of KOA. Additionally, the most common post-operative complication reported was deep peroneal nerve palsy., Conclusion: PFO is a viable knee joint preserving surgery for medial compartment KOA, however given the high risk for complications reported in the literature, surgeons should pay close attention to the neuroanatomical landmarks and techniques to avoid neurovascular injury., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Delhi Orthopedic Association. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Aims: Ischemic heart disease (IHD) has been a significant public health issue worldwide. This study aims to predict the global burden of IHD in a timely and comprehensive manner., Methods and Results: Incidence, prevalence, deaths, and disability-adjusted life years (DALYs) for IHD from 1990 to 2021 were derived from the Global Burden of Disease 2021 database and three models (linear, exponential, and Poisson regression) were used to estimate their trends over time at the global, regional, and national levels by age, sex, and country groups, with the gross domestic product per capita was applied to adjust the model. The model results revealed that the global burden of IHD is expected to increase continuously by 2050. By 2050, global IHD incidence, prevalence, deaths, and DALYs are projected to reach 67.3 million, 510 million, 16 million, and 302 million, respectively, which represents an increase of 116%, 106%, 80%, and 62% from 2021. Moreover, the results showed that regions with lower socio-demographic index (SDI) bore a greater burden of IHD than those with higher SDI, with men having a higher burden of IHD than women. People over 70 years old account for a major part of the burden of IHD, and premature death of IHD is also becoming more serious., Conclusion: The global burden of IHD will increase further by 2050, potentially due to population aging and economic disparities. Hence, it is necessary to strengthen the prevention of IHD and formulate targeted strategies according to different SDI regions and special populations., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The Hamiltonian, which determines the evolution of a quantum system, is fundamental in quantum physics. Therefore, it is crucial to implement high-precision generation and measurement of the Hamiltonian in a practical quantum system. Here, we experimentally demonstrate ultrahigh-precision Hamiltonian parameter estimation with a significant quantum advantage in a superconducting circuit via sequential control. We first observe the commutation relation for noncommuting operations determined by the system Hamiltonian, both with and without adding quantum control, verifying the commuting property of controlled noncommuting operations. Based on this control-induced commuting property, we further demonstrate Hamiltonian parameter estimation for polar and azimuth angles in superconducting circuits, achieving ultrahigh metrological gains in measurement precision exceeding the standard quantum limit by up to 16.0 and 16.1 dB at N=100, respectively.

Main Conclusion: The SiMBR genes in foxtail millet were identified and studied. Heterologous expression of SiMBR2 in Arabidopsis can improve plant tolerance to drought stress by decreasing the level of reactive oxygen species. Foxtail millet (Setaria italica L.), a C4 crop recognized for its exceptional resistance to drought stress, presents an opportunity to improve the genetic resilience of other crops by examining its unique stress response genes and understanding the underlying molecular mechanisms of drought tolerance. In our previous study, we identified several genes linked to drought stress by transcriptome analysis, including SiMBR2 (Seita.7G226600), a member of the MED25 BINDING RING-H2 PROTEIN (MBR) gene family, which is related to protein ubiquitination. Here, we have identified ten SiMBR genes in foxtail millet and conducted analyses of their structural characteristics, chromosomal locations, cis-acting regulatory elements within their promoters, and predicted transcription patterns specific to various tissues or developmental stages using bioinformatic approaches. Further investigation of the stress response of SiMBR2 revealed that its transcription is induced by treatments with salicylic acid and gibberellic acid, as well as by salt and osmotic stresses, while exposure to high or low temperatures led to a decrease in its transcription levels. Heterologous expression of SiMBR2 in Arabidopsis thaliana enhanced the plant's tolerance to water deficit by reducing the accumulation of reactive oxygen species under drought stress. In summary, this study provides support for exploring the molecular mechanisms associated with drought resistance of SiMBR genes in foxtail millet and contributing to genetic improvement and molecular breeding in other crops., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Depression is a major psychological disorder with a growing impact worldwide. Traditional methods for detecting the risk of depression, predominantly reliant on psychiatric evaluations and self-assessment questionnaires, are often criticized for their inefficiency and lack of objectivity. Advancements in deep learning have paved the way for innovations in depression risk detection methods that fuse multimodal data. This paper introduces a novel framework, the Audio, Video, and Text Fusion-Three Branch Network (AVTF-TBN), designed to amalgamate auditory, visual, and textual cues for a comprehensive analysis of depression risk. Our approach encompasses three dedicated branches-Audio Branch, Video Branch, and Text Branch-each responsible for extracting salient features from the corresponding modality. These features are subsequently fused through a multimodal fusion (MMF) module, yielding a robust feature vector that feeds into a predictive modeling layer. To further our research, we devised an emotion elicitation paradigm based on two distinct tasks-reading and interviewing-implemented to gather a rich, sensor-based depression risk detection dataset. The sensory equipment, such as cameras, captures subtle facial expressions and vocal characteristics essential for our analysis. The research thoroughly investigates the data generated by varying emotional stimuli and evaluates the contribution of different tasks to emotion evocation. During the experiment, the AVTF-TBN model has the best performance when the data from the two tasks are simultaneously used for detection, where the F1 Score is 0.78, Precision is 0.76, and Recall is 0.81. Our experimental results confirm the validity of the paradigm and demonstrate the efficacy of the AVTF-TBN model in detecting depression risk, showcasing the crucial role of sensor-based data in mental health detection., Competing Interests: The authors declare no conflicts of interest.

Human pluripotent stem cell-derived β cells (hPSC-β cells) show the potential to restore euglycemia. However, the immature functionality of hPSC-β cells has limited their efficacy in application. Here, by deciphering the continuous maturation process of hPSC-β cells post transplantation via single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we show that functional maturation of hPSC-β cells is an orderly multistep process during which cells sequentially undergo metabolic adaption, removal of negative regulators of cell function, and establishment of a more specialized transcriptome and epigenome. Importantly, remodeling lipid metabolism, especially downregulating the metabolic activity of ceramides, the central hub of sphingolipid metabolism, is critical for β cell maturation. Limiting intracellular accumulation of ceramides in hPSC-β cells remarkably enhanced their function, as indicated by improvements in insulin processing and glucose-stimulated insulin secretion. In summary, our findings provide insights into the maturation of human pancreatic β cells and highlight the importance of ceramide homeostasis in function acquisition., Competing Interests: Declaration of interests H.D. is an advisory board member of Cell Stem Cell. X.W., Y.J., H.H., and Y.P. are inventors on a patent (international application no. PCT/CN2023/137560; title “Method for differentiating pancreatic beta cells”)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The discipline development is the pillar for the development of traditional Chinese medicine( TCM). The academic progress in TCM is the commanding height of the discipline development of TCM. To lead and promote the development and academic progress of TCM, the China Association of Chinese Medicine has summarized the Top Ten Academic Achievements in Traditional Chinese Medicine during 2020-2022, the Major Scientific Problems, Engineering Technical Problems, and Industrial Technical Problems in Traditional Chinese Medicine during 2019-2023, and the Remarkable Research Achievements of Traditional Chinese Medicine during 2012-2022. Based on the above research reports and the research achievements awarded the national science and technology prizes in TCM in the last 20 years and according to the current situation and layout of TCM discipline development, this paper reviews the major research achievements of TCM in the last two decades and the latest research progress in TCM during 2020-2023. The major scientific, engineering technical, and industrial technical problems in TCM are analyzed and the emerging trends of TCM are prospected in accordance with the development laws and characteristics of TCM. This review provides new ideas and reference for the high-quality development of TCM in the new era.

Recent studies show that greenhouse gas (GHG) emissions from urban landscape water are significant and cannot be overlooked, underscoring the need to develop effective strategies for mitigating GHG production from global freshwater systems. Calcium peroxide (CaO 2 ) is commonly used as an eco-friendly reagent for controlling eutrophication in water bodies, but whether CaO 2 can reduce GHG emissions remains unclear. This study investigated the effects of CaO 2 dosage on the production of methane (CH 4 ) and nitrous oxide (N 2 O) in urban landscape water under anoxic conditions during summer. The findings reveal that CaO 2 addition not only improved the physicochemical and organoleptic properties of simulated urban landscape water but also reduced N 2 O production by inhibiting the activity of denitrifying bacteria across various dosages. Moreover, CaO 2 exhibited selective effects on methanogens. Specifically, the abundance of acetoclastic methanogen Methanosaeta and methylotrophic methanogen Candidatus&#95;Methanofastidiosum increased whereas the abundance of the hydrogenotrophic methanogen Methanoregula decreased at low, medium, and high dosages, leading to higher CH 4 production at increased CaO 2 dosage. A comprehensive multi-objective evaluation indicated that an optimal dosage of 60 g CaO 2 /m 2 achieved 41.21 % and 84.40 % reductions in CH 4 and N 2 O production, respectively, over a 50-day period compared to the control. This paper not only introduces a novel approach for controlling the production of GHGs, such as CH 4 and N 2 O, from urban landscape water but also suggests a methodology for optimizing CaO 2 dosage, providing valuable insights for its practical application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: This study evaluates the efficacy of a nomogram for predicting the pathology upgrade of apical prostate cancer (PCa)., Methods: A total of 754 eligible patients were diagnosed with apical PCa through combined systematic and magnetic resonance imaging (MRI)-targeted prostate biopsy followed by radical prostatectomy (RP) were retrospectively identified from two hospitals (training: 754, internal validation: 182, internal-external validation: 148). A nomogram for the identification of apical tumors in high-risk pathology upgrades through comparing the results of biopsy and RP was established incorporating statistically significant risk factors based on univariable and multivariable logistic regression. The nomogram's performance was assessed via the receiver operating characteristic (ROC) curve, calibration plots, and decision curve analysis (DCA)., Results: Univariable and multivariable analysis identified age, targeted biopsy, number of targeted cores, TNM stage, and the prostate imaging-reporting and data system score as significant predictors of apical tumor pathological progression. Our nomogram, based on these variables, demonstrated ROC curves for pathology upgrade with values of 0.883 (95% CI, 0.847-0.929), 0.865 (95% CI, 0.790-0.945), and 0.840 (95% CI, 0.742-0.904) for the training, internal validation and internal-external validation cohorts respectively. Calibration curves showed good consistency between the predicted and actual outcomes. The validation groups also showed great generalizability with the calibration curves. DCA results also demonstrated excellent performance for our nomogram with positive benefit across a threshold probability range of 0-0.9 for the training and internal validation group, and 0-0.6 for the internal-external validation group., Conclusion: The nomogram, integrating clinical, radiological, and pathological data, effectively predicts the risk of pathology upgrade in apical PCa tumors. It holds significant potential to guide clinicians in optimizing the surgical management of these patients., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

EEG neurofeedback using frontal alpha asymmetry (FAA) has been widely used for emotion regulation, but its effectiveness is controversial. Studies indicated that individual differences in neurofeedback training can be traced to neuroanatomical and neurofunctional features. However, they only focused on regional brain structure or function and overlooked possible neural correlates of the brain network. Besides, no neuroimaging predictors for FAA neurofeedback protocol have been reported so far. We designed a single-blind pseudo-controlled FAA neurofeedback experiment and collected multimodal neuroimaging data from healthy participants before training. We assessed the learning performance for evoked EEG modulations during training (L1) and at rest (L2), and investigated performance-related predictors based on a combined analysis of multimodal brain networks and graph-theoretical features. The main findings of this study are described below. First, both real and sham groups could increase their FAA during training, but only the real group showed a significant increase in FAA at rest. Second, the predictors during training blocks and at rests were different: L1 was correlated with the graph-theoretical metrics (clustering coefficient and local efficiency) of the right hemispheric gray matter and functional networks, while L2 was correlated with the graph-theoretical metrics (local and global efficiency) of the whole-brain and left the hemispheric functional network. Therefore, the individual differences in FAA neurofeedback learning could be explained by individual variations in structural/functional architecture, and the correlated graph-theoretical metrics of learning performance indices showed different laterality of hemispheric networks. These results provided insight into the neural correlates of inter-individual differences in neurofeedback learning., Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09939-x., Competing Interests: Conflict of interestThe authors declare that they have no competing interests., (© The Author(s), under exclusive licence to Springer Nature B.V. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Leuprorelin acetate microspheres, a common gonadotropin-releasing hormone agonist, have certain clinical benefits for prostate cancer (PCa). The present study aimed to compare the efficacy and safety of generic and branded leuprorelin acetate microspheres in patients with PCa. The present retrospective, observational study included 116 patients with PCa who received generic (Boennuokang ® ; Beijing Biote Pharmaceutical Co., Ltd.) or branded (Enantone ® ; Takeda Pharmaceutical Company, Ltd.) leuprorelin acetate microspheres via injection (commonly 3.75 mg once every 4 weeks), defined as the test (n=64) and reference (n=52) groups, respectively. The present study showed that testosterone levels at month (M) 3 (P<0.001), M6 (P=0.012) and M12 (P<0.001) were decreased in the test group compared with the reference group. However, prostate-specific antigen (PSA) levels at baseline, M1, M3, M6 and M12 were not significantly different between the test and reference groups (all P>0.05). The median (interquartile range) testosterone and PSA levels at M12 were 15.50 ng/dl (10.00-31.25 ng/dl) and 0.01 ng/ml (0.01-0.10 ng/ml), respectively, in the test group and 28.00 ng/dl (22.00-37.00 ng/dl) and 0.02 ng/ml (0.01-0.16 ng/ml), respectively, in the reference group. No significant differences were observed in the M1-baseline, M3-baseline, M6-baseline and M12-baseline changes of testosterone or PSA levels between the two groups (all P>0.050). Additionally, the incidence of all adverse events was not significantly different between the two groups (all P>0.050). Overall, Boennuokang ® leuprorelin acetate microspheres exhibited a similar efficacy for suppression of testosterone and PSA levels with a comparable safety profile compared with Enantone ® leuprorelin acetate microspheres in patients with PCa., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024, Spandidos Publications.)