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Abstract Background Diabetic retinopathy (DR), the principal cause of acquired blindness among the working-age population, is the most frequent microvascular complication of diabetes. Although metabolic disorders are hypothesized to play a role in its pathogenesis, the underlying mechanism remains largely elusive. Methods To elucidate the mechanism, we initially compared metabolite profiles of vitreous fluid between 23 patients with DR and 12 non-diabetic controls using liquid chromatography/tandem mass spectrometry, identifying the distinct metabolite indoxyl sulfate (IS). Subsequently, streptozotocin (STZ)-induced diabetic and IS-injected rat models were established to examine the effects of IS on retinal microvasculature. RNA sequencing was conducted to identify potential regulatory mechanisms in IS-treated human retinal endothelial cells (HREC). Finally, target gene knockdown in HREC and treatment of IS-injected rats with inhibitors (targeting IS production or downstream regulators) were employed to elucidate the detailed mechanisms and identify therapeutic targets for DR. Results Metabolomics identified 172 significantly altered metabolites in the vitreous humor of diabetics, including the dysregulated tryptophan metabolite indoxyl sulfate (IS). IS was observed to breach the blood-retinal barrier and accumulate in the intraocular fluid of diabetic rats. Both in vivo and in vitro experiments indicated that elevated levels of IS induced endothelial apoptosis and disrupted cell junctions. RNA sequencing pinpointed prostaglandin E2 (PGE2) synthetase-cyclooxygenase 2 (COX-2) as a potential target of IS. Validation experiments demonstrated that IS enhanced COX-2 expression, which subsequently increased PGE2 secretion by promoting transcription factor EGR1 binding to COX-2 DNA following entry into cells via organic anion transporting polypeptides (OATP2B1). Furthermore, inhibition of COX-2 in vivo or silencing EGR1/OATP2B1 in HREC mitigated IS-induced microcapillary damage and the activation of COX-2/PGE2. Conclusion Our study demonstrated that indoxyl sulfate (IS), a uremic toxin originating from the gut microbiota product indole, increased significantly and contributed to retinal microvascular damage in diabetic retinopathy (DR). Mechanistically, IS impaired retinal microvascular integrity by inducing the expression of COX-2 and the production of PGE2. Consequently, targeting the gut microbiota or the PGE2 pathway may offer effective therapeutic strategies for the treatment of DR. Graphical Abstract

Abstract Recent studies have increasingly focused on the effect of relativistic motion on quantum coherence. Prior research predominantly examined the influence of relative motion on basis-dependent quantum coherence, underscoring its susceptibility to decoherence under accelerated conditions. Yet, the effect of relativistic motion on basis-independent quantum coherence, which is critical for understanding the intrinsic quantum features of a system, remains an interesting open question. This paper addresses this question by examining how total, collective, and localized coherence are affected by acceleration and coupling strength. Our analysis reveals that both total and collective coherence significantly decrease with increasing acceleration and coupling strength, ultimately vanishing at high levels of acceleration. This underscores the profound impact of Unruh thermal noise. Conversely, localized coherence exhibits relative stability, decreasing to zero only under the extreme condition of infinite acceleration. Moreover, we demonstrate that collective, localized, and basis-independent coherence collectively satisfy the triangle inequality. These findings are crucial for enhancing our understanding of quantum information dynamics in environments subjected to high acceleration and offer valuable insights on the behavior of quantum coherence under relativistic conditions.

Quantum secure direct communication (QSDC) can directly transmit secret messages through quantum channel without keys. Device-independent (DI) QSDC guarantees the message security relying only on the observation of the Bell-inequality violation, but not on any detailed description or trust of the devices’ inner workings. Compared with conventional QSDC, DI-QSDC has relatively low secret message capacity. To increase DI-QSDC’s secret messages capacity, we propose a high-capacity DI-QSDC protocol based on the hyper-encoding technique. The total message leakage rate of our DI-QSDC protocol only relies on the most robust degree of freedom. We provide the numerical simulation of its secret message capacity altered with the communication distance. Our work serves as an important step toward the further development of DI-QSDC systems.

The regulation of the cell cycle is essential for maintaining normal cellular function, especially in the development of diseases such as lung cancer. The cell cycle consists of four major phases (G1, S, G2 and M phases), which are characterized by a series of precise molecular events to ensure proper cell proliferation and division. In lung cancer cells, cell cycle dysregulation can lead to disordered proliferation and increased invasiveness of cancer cells. G2 and S-phase expressed 1 (GTSE1) is a regulatory protein found in the cytoplasm of the cell, which plays a key role in the cell cycle distribution of a wide range of cancer cells and is involved in life processes such as cell proliferation and apoptosis. GTSE1 affects cell cycle progression by interacting with cyclin-dependent kinase inhibitor 1A (p21) and maintaining the stability of p21, which in turn inhibits the activity of cyclin-dependent kinase 1/2 (CDK1/2). In addition, GTSE1 is also involved in the regulation of tumor protein 53 (p53) signaling pathway. With the assistance of mouse double minute 2 homolog (MDM2), GTSE1 is able to transport p53 from the nucleus to the cytoplasm and promote its ubiquitination and degradation, thus affecting cell cycle and cell death-related signaling pathways. This paper reviews the expression of GTSE1 in lung cancer cells and its effects on lung cancer, as well as its potential mechanisms involved in cell cycle regulation.

Abstract In the past two decades, the exploration of quantumness within Schwarzschild spacetime has garnered significant interest, particularly regarding the Hawking radiation’s impact on quantum correlations and quantum coherence. Building on this foundation, we investigate how Hawking radiation influences maximal steered coherence (MSC)-a crucial measure for gauging the ability to generate coherence through steering. We find that as the Hawking temperature increases, the physically accessible MSC degrade while the unaccessible MSC increase. This observation is attributed to a redistribution of the initial quantum correlations, previously acknowledged by inertial observers, across all bipartite modes. In particular, we find that in limit case that the Hawking temperature tends to infinity, the accessible MSC equals to $$1/\sqrt{2}$$ 1 / 2 of its initial value, and the unaccessible MSC between mode A and $$\overline{B}$$ B ¯ also equals to the same value. Our findings illuminate the intricate dynamics of quantum information in the vicinity of black holes, suggesting that Hawking radiation plays a pivotal role in reshaping the landscape of quantum coherence and entanglement in curved spacetime. This study not only advances our theoretical understanding of black hole thermodynamics but also opens new avenues for investigating the interface between quantum mechanics and general relativity.

Facial age recognition has been widely used in real-world applications. Most of current facial age recognition methods use deep learning to extract facial features to identify age. However, due to the high dimension features of faces, deep learning methods might extract a lot of redundant features, which is not beneficial for facial age recognition. To improve facial age recognition effectively, this paper proposed the deep manifold learning (DML), a combination of deep learning and manifold learning. In DML, deep learning was used to extract high-dimensional facial features, and manifold learning selected age-related features from these high-dimensional facial features for facial age recognition. Finally, we validated the DML on Multivariate Observations of Reactions and Physical Health (MORPH) and Face and Gesture Recognition Network (FG-NET) datasets. The results indicated that the mean absolute error (MAE) of MORPH is 1.60 and that of FG-NET is 2.48. Moreover, compared with the state of the art facial age recognition methods, the accuracy of DML has been greatly improved.

ObjectiveThe significance of interstitial cells of Cajal (ICC) in the gastrointestinal tract has garnered increasing attention. In recent years, approximately 80 articles on ICC have been published annually in various journals. However, no bibliometric study has specifically focused on the literature related to ICC. Therefore, we conducted a comprehensive bibliometric analysis of ICC to reveal dynamic scientific developments, assisting researchers in exploring hotspots and emerging trends while gaining a global perspective.MethodsWe conducted a literature search in the Web of Science Core Collection (WoSCC) from January 1, 2013, to December 31, 2023, to identify relevant literature on ICC. We employed bibliometric software, namely VOSviewer and CiteSpace, to analyze various aspects including annual publication output, collaborations, research hotspots, current status, and development trends in this domain.ResultsA total of 891 English papers were published in 359 journals by 928 institutions from 57 countries/regions. According to the keyword analysis of the literature, researchers mainly focused on “c-Kit,” “expression,” “smooth muscle,” and “nitric oxide” related to ICC over the past 11 years. However, with “SIP syncytium,” “ANO1,” “enteric neurons,” “gastrointestinal stromal tumors (GIST),” and “functional dyspepsia (FD),” there has been a growing interest in the relationship between ANO1, SIP syncytium, and ICC, as well as the role of ICC in the treatment of GIST and FD.ConclusionBibliometric analysis has revealed the current status of ICC research. The association between ANO1, SIP syncytium, enteric neurons and ICC, as well as the role of ICC in the treatment of GIST versus FD has become the focus of current research. However, further research and collaboration on a global scale are still needed. Our analysis is particularly valuable to researchers in gastroenterology, oncology, and cell biology, providing insights that can guide future research directions.

Abstract Objective Early identification of cognitive impairment in neurodegenerative diseases like Alzheimer's disease (AD) is crucial. Neurofilament, a potential biomarker for neurological disorders, has gained attention. Our study aims to investigate the relationship between serum neurofilament light (sNfL) levels and cognitive function in elderly individuals in the United States. Methods This cross‐sectional study analyzed data from participants aged 60 and above in the National Health and Nutrition Examination Survey (2013–2014). We collected sNfL levels, cognitive function tests, sociodemographic characteristics, comorbidities, and other variables. Weighted multiple linear regression models examined the relationship between ln(sNfL) and cognitive scores. Restricted cubic spline (RCS) visualization explored nonlinear relationships. The stratified analysis examined subgroups' ln(sNfL) and cognitive function association. Results The study included 446 participants (47.73% male). Participants with ln(sNfL) levels between 2.58 and 2.81 pg/mL (second quintile) performed relatively well in cognitive tests. After adjusting for multiple factors, ln(sNfL) levels were negatively correlated with cognitive function, with adjusted β (95% CI) as follows: immediate recall test (IRT): −0.763 (−1.301 to −0.224), delayed recall test (DRT): −0.308 (−0.576 to −0.04), animal fluency test (AFT): −1.616 (−2.639 to −0.594), and digit symbol substitution test (DSST): −2.790 (−4.369 to −1.21). RCS curves showed nonlinear relationships between ln(sNfL) and DRT, AFT, with inflection points around 2.7 pg/mL. The stratified analysis revealed a negative correlation between ln(sNfL) and cognition in specific subgroups with distinct features, with an interaction between diabetes and ln(sNfL). Interpretation Higher sNfL levels are associated with poorer cognitive function in the elderly population of the United States. sNfL shows promise as a potential biomarker for early identification of cognitive decline.

Ligusticum Chuanxiong, a perennial herb of considerable medicinal value commonly known as Chuanxiong, holds pivotal importance in sliced form for ensuring quality and regulating markets through geographical origin identification. This study introduces an integrated approach utilizing Near-Infrared Spectroscopy (NIRS) and Convolutional Neural Networks (CNNs) to establish an efficient method for rapidly determining the geographical origin of Chuanxiong slices. A dataset comprising 300 samples from 6 distinct origins was analyzed using a 1D-CNN model. In this study, we initially established a traditional classification model. By utilizing the Spectrum Outlier feature in TQ-Analyst 9 software to exclude outliers, we have enhanced the performance of the model. After evaluating various spectral preprocessing techniques, we selected Savitzky–Golay filtering combined with Multiplicative Scatter Correction (S-G + MSC) to process the raw spectral data. This approach significantly improved the predictive accuracy of the model. After 2000 iterations of training, the CNN model achieved a prediction accuracy of 92.22%, marking a 12.09% improvement over traditional methods. The application of the Class Activation Mapping algorithm not only visualized the feature extraction process but also enhanced the traditional model’s classification accuracy by an additional 7.41% when integrated with features extracted from the CNN model. This research provides a powerful tool for the quality control of Chuanxiong slices and presents a novel perspective on the quality inspection of other agricultural products.

Abstract The assembly of cluster-based π-stacked porous supramolecular frameworks presents daunting challenges, including the design of suitable cluster building units, control of the sufficient C-H···π interactions, trade-off between structural dynamics and stability as well as understanding the resulting collective properties. Herein, we report a cluster-based C-H···π interaction-stacked porous supramolecular framework, namely, Cu12a-π, consisting of Cu12 nanocluster as a 6-connected node, which is further propagated to a dynamic porous supramolecular frameworks via dense intralayer C-H···π interactions, yielding permanent porosity. In addition, Cu12a-π can be transformed into cluster-based nonporous adaptive crystals (Cu12b-NACs) via ligand-exchange following a dissociation-reassembly mechanism. Moreover, Cu12a-π can efficiently remove 97.2% of iodine from saturated iodine aqueous solutions with a high uptake capacity of 2.96 g·g−1. These prospective results positioned at cluster-based porous supramolecular framework and enlighten follow-up researchers to design and synthesize such materials with better performance.

To solve the problems of line overload tripping and cascading faults caused by power flow transfer in power systems， an optimal control strategy for grid overload considering energy storage and electrothermal characteristics of transmission lines is proposed. Firstly， the variation of electrothermal characteristics of transmission lines is analyzed. Based on meteorological data from various observation stations covered by transmission corridors in practical power grids， a method for calculating conductor temperatures considering meteorological distribution is formulated to enhance the accuracy of estimating line overload capacity. Furthermore， to minimize the control cost， an optimized control model incorporating energy storage for power system overload is established. The simulated annealing particle swarm optimization algorithm is used to solve the model， swiftly determining the optimal control and adjustment quantities and thereby fully leveraging the energy storage regulation capability and line overload tolerance capacity to effectively prevent cascading faults in the power grid. Finally， the effectiveness of the proposed control method is validated using the improved IEEE 39-node system.

Abstract The loss of HES1, a canonical Notch signaling target, may cooperate with KRAS mutations to remodel the extracellular matrix and to suppress the anti-tumor immune response. While HES1 expression is normal in benign hyperplastic polyps and normal colon tissue, HES1 expression is often lost in sessile serrated adenomas/polyps (SSAs/SSPs) and colorectal cancers (CRCs) such as those right-sided CRCs that commonly harbor BRAF or KRAS mutations. To develop a deeper understanding of interaction between KRAS and HES1 in colorectal carcinogenesis, we selected microsatellite stable (MSS) and KRAS mutant or KRAS wild type CRCs that show aberrant expression of HES1 by immunohistochemistry. By comparing the transcriptional landscapes of microsatellite stable (MSS) CRCs with or without nuclear HES1 expression, we investigated differentially expressed genes and activated pathways. We identified pathways and markers in the extracellular matrix and immune microenvironment that are associated with mutations in KRAS. We found that loss of HES1 expression positively correlated with matrix remodeling and epithelial-mesenchymal transition but negatively correlated with tumor cell proliferation. Furthermore, loss of HES1 expression in KRAS mutant CRCs correlates with a higher M2 macrophage polarization and activation of IL6 and IL10 immunosuppressive signature. Identifying these HES1-related markers may be useful for prognosis stratification and developing treatment for KRAS-mutant CRCs.

Abstract Background Fusobacterium nucleatum (Fn) acts as a procarcinogenic bacterium in colorectal carcinoma (CRC) by regulating the inflammatory tumor microenvironment (TME). Neutrophil extracellular traps (NETs), which can be generated by persistent inflammation, have been recently considered to be significant contributors in promoting cancer progression. However, whether NETs are implicated in Fn-related carcinogenesis is still poorly characterized. Here, we explored the role of NETs in Fn-related CRC as well as their potential clinical significance. Methods Fn was measured in tissue specimens and feces samples from CRC patients. The expression of NET markers were also detected in tissue specimens, freshly isolated neutrophils and blood serum from CRC patients, and the correlation of circulating NETs levels with Fn was evaluated. Cell-based experiments were conducted to investigate the mechanism by which Fn modulates NETs formation. In addition, we clarified the functional mechanism of Fn-induced NETs on the growth and metastasis of CRC in vitro and in vivo experiments. Results Tissue and blood samples from CRC patients, particularly those from Fn-infected CRC patients, exhibited greater neutrophil infiltration and higher NETs levels. Fn infection induced abundant NETs production in in vitro studies. Subsequently, we demonstrated that Fn-induced NETs indirectly accelerated malignant tumor growth through angiopoiesis, and facilitated tumor metastasis, as manifested by epithelial-mesenchymal transition (EMT)-related cell migration, matrix metalloproteinase (MMP)-mediated basement membrane protein degradation, and trapping of CRC cells. Mechanistically, the Toll-like receptor (TLR4)-reactive oxygen species (ROS) signaling pathway and NOD-like receptor (NOD1/2)-dependent signaling were responsible for Fn-stimulated NETs formation. More importantly, circulating NETs combined with carcinoembryonic antigen (CEA) could predict CRC occurrence and metastasis, with areas under the ROC curves (AUCs) of 0.92 and 0.85, respectively. Conclusions Our findings indicated that Fn-induced NETs abundance by activating TLR4-ROS and NOD1/2 signalings in neutrophils facilitated CRC progression. The combination of circulating NETs and CEA was identified as a novel screening strategy for predicting CRC occurrence and metastasis.

Structural-colored fabrics have been attracting much attention due to their eco-friendliness, dyelessness, and anti-fading properties. Monodisperse microspheres of metal, metal oxide, and semiconductors are promising materials for creating photonic crystals and structural colors owing to their high refractive indices. Herein, Cu2O microspheres were prepared by a two-step reduction method at room temperature; the size of Cu2O microspheres was controlled by changing the molar ratio of citrate to Cu2+; and the size of Cu2O microspheres was tuned from 275 nm to 190 nm. The Cu2O microsphere dispersions were prepared with the monodispersity of Cu2O microspheres. Furthermore, the effect of the concentration of Cu2O microsphere and poly(butyl acrylate) on the structural color was also evaluated. Finally, the stability of the structural color against friction and bending was also tested. The results demonstrated that the different structural colors of fabrics were achieved by adjusting the size of the Cu2O microsphere, and the color fastness of the structural color was improved by using poly(butyl acrylate) as the adhesive.

Muscle fatigue represents the most prevalent symptom of long-term COVID, with elusive pathogenic mechanisms. We performed a longitudinal study to characterize histopathological and transcriptional changes in skeletal muscle in a hamster model of respiratory SARS-CoV-2 infection and compared them with influenza A virus (IAV) and mock infections. Histopathological and bulk RNA sequencing analyses of leg muscles derived from infected animals at days 3, 30, and 60 post-infection showed no direct viral invasion but myofiber atrophy in the SARS-CoV-2 group, which was accompanied by persistent downregulation of the genes related to myofibers, ribosomal proteins, fatty acid β-oxidation, tricarboxylic acid cycle, and mitochondrial oxidative phosphorylation complexes. While both SARS-CoV-2 and IAV infections induced acute and transient type I and II interferon responses in muscle, only the SARS-CoV-2 infection upregulated TNF-α/NF-κB but not IL-6 signaling in muscle. Treatment of C2C12 myotubes, a skeletal muscle cell line, with combined IFN-γ and TNF-α but not with IFN-γ or TNF-α alone markedly impaired mitochondrial function. We conclude that a respiratory SARS-CoV-2 infection can cause myofiber atrophy and persistent energy metabolism suppression without direct viral invasion. The effects may be induced by the combined systemic interferon and TNF-α responses at the acute phase and may contribute to post-COVID-19 persistent muscle fatigue.

Glaucoma is the leading cause of irreversible blindness worldwide. In the pathogenesis of glaucoma, activated microglia can lead to retinal ganglion cells (RGCs) apoptosis and death, however, the molecular mechanisms remain largely unknown. We demonstrate that phospholipid scramblase 1 (PLSCR1) is a key regulator promoting RGCs apoptosis and their clearance by microglia. As evidenced in retinal progenitor cells and RGCs of the acute ocular hypertension (AOH) mouse model, overexpressed PLSCR1 induced its translocation from the nucleus to the cytoplasm and cytomembrane, as well as elevated phosphatidylserine exposure and reactive oxygen species generation with subsequent RGCs apoptosis and death. These damages were effectively attenuated by PLSCR1 inhibition. In the AOH model, PLSCR1 led to an increase in M1 type microglia activation and retinal neuroinflammation. Upregulation of PLSCR1 resulted in strongly elevated phagocytosis of apoptotic RGCs by activated microglia. Taken together, our study provides important insights linking activated microglia to RGCs death in the glaucoma pathogenesis and other RGC-related neurodegenerative diseases.

Abstract The role of G2 and S phase‐expressed‐1 (GTSE1), a microtubule‐localized protein, in non‐small‐cell lung cancer (NSCLC) remains unknown. We explored its role in NSCLC growth. GTSE1 was detected in NSCLC tissues and cell lines using quantitative real‐time polymerase chain reaction. The clinical significance of GTSE1 levels was evaluated. Biological and apoptotic effects of GTSE1 were evaluated using transwell, cell‐scratch, and MTT assays, and flow cytometry and western blotting, respectively. Its association with cellular microtubules was shown by western blotting and immunofluorescence. GTSE1 expression was upregulated in NSCLC tissues and cell lines. GTSE1 levels correlated with lymph node metastasis. Higher GTSE1 mRNA expression correlated with shorter progression‐free survival. GTSE1‐knockdown decreased proliferation, colony formation, invasion, and migration of NSCLC cells, and inhibited tau and stathmin‐1 microtubule‐associated protein expression, via the extracellular‐regulated protein kinase/mitogen‐activated protein kinase (ERK/MAPK) signaling pathway, and microtubule disruption. GTSE1 may promote NSCLC growth by regulating tau and stathmin‐1 through the ERK/MAPK signaling pathway.

Purpose: Increased incidence of anterior cruciate ligament injuries has amplified the need for quantitative research in clinical and academic settings. We used a novel digital arthrometer to measure knee laxity in healthy people and patients with anterior cruciate ligament injuries. Changes in stiffness were also assessed to develop new indicators for detecting anterior cruciate ligament injury. The purpose of this study was to use arthrometer to measure the quantitative indicator of knee laxity, bringing clinicians a new perspective on how to identify injury to the ACL.Methods: In this cross-sectional study, anterior tibial displacement under continuous loading was measured using a novel digital arthrometer in 30 patients with unilateral anterior cruciate ligament injury and 30 healthy controls. Load-displacement curves were plotted, using real-time load and displacement changes. Stiffness was defined by the slope of the applied load to tibial displacement. Anterior tibial displacement and instantaneous stiffness values under different loads were compared. The restricting contribution of the anterior cruciate ligament transformed the displacement-stiffness curve from a sharp decrease to a stable increase, resulting in a minimum stiffness value. Using the minimum stiffness as the turning point, the load-displacement curve was divided into regions 1 and 2. The two regions’ stiffness changes were compared. Based on the findings, receiver operating characteristic curves were plotted and the area under the curve was calculated to estimate the diagnostic accuracy.Results: Anterior tibial displacement was significantly greater in the anterior cruciate ligament injury group than in the controls under each 10-N increase load (p < 0.05). In the anterior cruciate ligament injury group, instantaneous stiffness was significantly lower on the injured side than on the healthy side (p < 0.05). In the two regions of the load-displacement curve, stiffness was significantly lower in the anterior cruciate ligament injury group than in the control group (all, p < 0.05). Receiver operating characteristic curves were plotted, using changes in stiffness under the two regions in both groups. Stiffness in region 2 had the largest area under the curve (0.94; 95% CI, 0.88–0.99). Using the cut-off value of 9.62 N/mm to detect ACL injury, the sensitivity and specificity were 93% and 82%, respectively.Conclusion: Our investigation of ligament stiffness provides novel insights into the properties of knee laxity. Stiffness in the later stages of increased loading

Power flow solution of the system with a full-power converter may get lost during low-voltage ride-through （LVRT）. Therefore， the change law of grid equivalent parameters and power flow characteristics during the fault is analyzed， and the law of influence of different system variables on the existence of power flow solution is analyzed qualitatively by numerical calculation considering the control characteristics of the converter. Based on the variation law of the grid equivalent parameters and the real-time calculation of the determinant of the Jacobi matrix of power flow， an active current amplitude limiting and autoregulation method is proposed that only requires the non-fault grid equivalent parameters and the measured voltage at the grid-connected point. The simulation results show that the proposed method can ensure the existence of the power flow solution during LVRT and is conducive to the safe and stable operation of the power system.

Skeletal muscle is essential for body physical activity, energy metabolism, and temperature maintenance. It has excellent capabilities to maintain homeostasis and to regenerate after injury, which indispensably relies on muscle stem cells, satellite cells (MuSCs). The quiescence, activation, and differentiation of MuSCs are tightly regulated in homeostatic and regenerating muscles. Among the important regulators are intramuscular macrophages, which are functionally heterogeneous with different subtypes present in a spatiotemporal manner to regulate the balance of different MuSC statuses. During chronic injury and aging, intramuscular macrophages often undergo aberrant activation, which in turn disrupts muscle homeostasis and regenerative repair. Growing evidence suggests that the aberrant activation is mainly triggered by altered muscle microenvironment. The trained immunity that affects myeloid progenitors during hematopoiesis may also contribute. Aged immune system may contribute, in part, to the aging-related sarcopenia and compromised skeletal muscle injury repair. As macrophages are actively involved in the progression of many muscle diseases, manipulating their functional activation has become a promising therapeutic approach, which requires comprehensive knowledge of the cellular and molecular mechanisms underlying the diverse activation. To this end, we discuss here the current knowledge of multifaceted role of macrophages in skeletal muscle homeostasis, injury, and repair.

Abstract Despite the impressive progress of stimuli‐responsive fluorescent materials, little is known about the influence of confinement created by crystalline polymer over the fluorescence properties of fluorescent molecules. The effects of confinement on the fluorescence of an aggregation‐induced emission luminogen (AIEgen) are investigated using computational simulations, which reveal that the confined space induces the AIEgens to take a more planar conformation, resulting in a red‐shifted emission spectrum. With this property, the study is extended to explore the confinement generated by various polymer crystalline forms, and it is shown that different fluorescence colors are activated. This confinement fluorescence effect is attributed to the different spatial dimensions of the polymer amorphous layer between lamellar crystals where the AIEgens are located. These results indicate the immediate association between crystalline structure and fluorescence signals, activating unprecedented photophysical properties of luminescent materials, and also providing the possibility for crystalline structure visualization, it is important for the many polymer crystallization processes occurring in the materials processing.

Objective: Deleted in liver cancer 1 (DLC1) is a GTPase-activating protein that is reported as a suppressor in certain human cancers. However, the detailed biological function of DLC1 is still unclear in human prostate cancer (PCa). In the present study, we aimed to explore the function of DLC1 in PCa cells. Methods: Silencing and overexpression of DLC1 were induced in an androgen-sensitive PCa cell line (LNCaP) using RNA interference and lentiviral vector transduction. The Cell Counting Kit-8 assay was performed to determine cell proliferation. The cell cycle was examined by performing a propidium iodide staining assay. Results: Our results indicated that DLC1 overexpression markedly suppressed the proliferation and cell cycle progression of LNCaP cells. Moreover, DLC1 expression was negatively correlated with Rho-associated protein kinase (ROCK) expression in LNCaP cells. Importantly, this study showed that the ROCK inhibitor Y27632 restored the function of DLC1 in LNCaP cells and reduced the tumorigenicity of LNCaP cells in vivo. Conclusion: Our results indicated that DLC1 overexpression markedly suppressed the proliferation and cell cycle progression of PCa cells and negatively correlated with ROCK expression in PCa cells and tissue.

We study an excitation hopping on a one-dimensional (1D) dimer chain of coupled resonators with the alternate on-site photon energies, which interacts with a two-level emitter (TLE) by a coupling point or two adjacent coupling points. In the single-excitation subspace, this system not only possesses two energy bands with propagating states, but also possesses photonic bound states. The number of bound states depends on the coupling forms between the TLE and the dimer chain. It is found that when the TLE is locally coupled to one resonator of the dimer chain, the bound-state that has mirror reflection symmetry. When the TLE is nonlocally coupled to two adjacent resonators, three bound states with preferred direction arise due to the mirror symmetry breaking. By using chirality to measure the asymmetry, it is found that the chirality of these bound states can be tuned by changing the energy differences of single photon in the adjacent resonators, the coupling strengths and the transition energy of the TLE.

Taking Chinese A-share listed firms from 2014 to 2018 as our samples, this paper investigates the impact of regulatory information disclosure on corporate over-financialisation behaviour from comment letters. The empirical results show that financialisation-related comment letters can effectively reduce the behaviour of corporate over-financialisation, and this positive governance effect is more pronounced in companies with strong market arbitrage motivation. Further tests show that the more intensity of the financialisation-related comment letters, the higher the governance effect of comment letters on over-financialisation. Specifically, the governance effect of inquiries mechanism is more significant when the financialisation-related comment letters have the questions of “over-financialisation’. From the specific influence mechanism, the governance effect of financialisation-related comment letters is achieved by potential violation cost and the pressure of market attention. Finally, the governance effect of financialisation-related comment letters on over-financialisation can spill over to non-comment-letter-receivers in the same industry or in the same corporation groups.

BackgroundType III Bartter syndrome (BS) is an autosomal recessive disease caused by mutations in the CLCNKB (chloride voltage-gated channel Kb) gene that encodes CLC-Kb. CLC-Kb is mainly located in the thick ascending limb of Henle's loop and regulates chloride efflux from tubular epithelial cells to the interstitium. Type III BS is characterized by metabolic alkalosis, renal salt wasting, hyperreninemia, and hyperaldosteronism with normal blood pressure.Case presentationWe reported the case of a 3-day-old girl whose initial symptom we diagnosed as jaundice, but we accidentally found metabolic alkalosis. She showed recurrent metabolic alkalosis, hypokalemia, and hypochloremia and also had hyperreninemia and hyperaldosteronism with normal blood pressure. Both oral potassium supplements and potassium infusion therapy were unable to entirely restore the electrolyte imbalance. She was suspected of Bartter syndrome and genetic tests were performed on her and her parents. Next-generation sequencing identified CLCNKB gene mutation including heterozygous mutation c.1257delC (p.M421Cfs*58) and a low-level mutation c.595G > T (p.E199*); both mutations were also verified in the parents.ConclusionWe reported the case of a classic Bartter syndrome in a newborn with a heterozygous frameshift mutation and a mosaic non-sense mutation in the CLCNKB gene.

Epidemiological studies have suggested a potential relationship between the transforming growth factor-β1 (TGF-β1) gene and ischemic stroke (IS) risk; however, the current results are inconsistent. Therefore, we performed this meta-analysis to assess the precise association between TGF-β1 polymorphisms and IS risk. Online databases were searched for themes related to TGF-β1 polymorphisms and ARE risk. Quantitative calculations of odds ratios (ORs) and confidence intervals (CIs) were performed using 5 genetic models of each variant locus. Heterogeneity tests, cumulative analyses, sensitivity analyses, and publication bias were conducted to examine statistical power. Moreover, changes in the secondary structure and minimum free energy (MFE) were explored using in silico analysis. Nineteen case-control studies were included in our meta-analysis on rs1800468 G>A, rs1800469 C>T, and rs1800470 T>C polymorphisms and IS risk. Overall, only a marginal association was found between the rs1800469 C>T polymorphism and IS risk (T vs C: OR = 1.12, 95%CI = 1.00-1.46, P = .05, I 2 = 77.0%). Otherwise, no significant association was observed between the rs1800468 G>A and rs1800470 T>C polymorphisms and IS risk in general and stratified analyses. Moreover, no significant changes in secondary structure and MFE were found in any of the 3 polymorphic loci. Current evidence cautiously suggests that TGF-β1 polymorphisms are not associated with IS susceptibility.

BackgroundRetinal ganglion cells (RGCs) axon loss at the site of optic nerve head (ONH) is long believed as the common pathology in glaucoma since different types of glaucoma possessing different characteristic of intraocular pressure, and this damage was only detected at the later stage.MethodsTo address these disputes and detect early initiating events underlying RGCs, we firstly detected somatic or axonal change and compared their difference in acute and chronic phase of primary angle-closed glaucoma (PACG) patient using optical coherence tomography (OCT), then an axonal-enriched cytoskeletal protein neurofilament heavy chain and its phosphoforms (NF-H, pNF-H) were utilized to reveal spatio-temporal undetectable damage insulted by acute and chronic ocular hypertension (AOH, COH) in two well characterized glaucoma mice models.ResultsIn clinic, we detected nonhomogeneous changes such as ONH and soma of RGCs presenting edema in acute phase but atrophy in chronic one by OCT. In AOH animal models, an increase expression of NF-H especially its phosphorylation modification was observed as early as 4 h before RGCs loss, which presented as somatic accumulation in the peripheral retina and at the sites of ONH. In contrast, in microbeads induced COH model, NF-H and pNF-H reduced significantly, these changes firstly occurred as NF-H or pNF-H disconnection at ONH and optic nerve after 2 weeks when the intraocular pressure reaching the peak; Meanwhile, we detected aqueous humor pNF-H elevation after AOH and slight reduction in the COH.ConclusionTogether, our data supports that early alteration of NF-H and its phosphoforms would reveal undetectable subcellular damage consisting of peripheral somatic neurofilament compaction, impaired axonal transport and distal axonal disorganization of cytoskeleton beyond the ONH, and identifies two distinct axonal degeneration which were Wallerian combination with retrograde degeneration in acute PACG and retrograde degeneration in the chronic one.

Objective: Traditional knee braces unloading forces primarily from a single compartment are insufficient for patients with knee injuries or knee osteoarthritis (KOA) involving multiple compartments. We investigated how knee kinematics were altered by an overall unloading brace (OUB) designed to unload both the medial and lateral tibiofemoral (TF) compartments simultaneously during dynamic movement. Methods: Gait analysis was performed on 32 adults with normal knee alignment and no history of knee disease. Three-dimensional (3D) knee kinematic data collected during treadmill walking (3 km/h) and jogging (5 km/h) with an optical motion capture system were compared with versus without the OUB. Results: In the stance phase, wearing the OUB, versus not wearing it, increased the proximal-distal translational range of motion (ROM) of the knee by 4.04 mm (Effect size, ES = 0.97) during walking and by 3.43 mm (ES = 0.97) during jogging, decreased abduction-adduction rotational ROM by 3.09°(ES = 1.05) during walking and by 2.88°(ES = 1.50) during jogging, and decreased internal-external rotation by 2.14°(ES = 0.81) during walking and by 4.66°(ES = 1.61) during jogging. In the swing phase, the OUB increased proximal-distal translational ROM by 12.64 mm (ES = 1.31) during walking and by 9.23 mm (ES = 0.92) during jogging, decreased abduction-adduction rotational ROM by 2.83°(ES = 0.54) during walking and by 3.37°(ES = 0.67) during jogging, and decreased internal-external rotational ROM by 2.71°(ES = 0.68) during jogging. Conclusions: OUB use increased proximal-distal translation while reducing abduction-adduction rotation. This effect may increase the joint gap of the tibiofemoral joint, thereby reducing joint stress, and may contribute to disease rehabilitation in the knee of clinical orthopedics, rehabilitation, and sports medicine fields. However, additional studies are needed to assess the range of possible clinical and prophylactic benefits of OUB.

Abstract Properties can be tailored by tuning composition in high-order composition spaces. For spaces with complex phase behavior, modeling the properties as a function of composition and phase distribution remains a formidable challenge. We present materials structure–property factorization (MSPF) as an approach to automate modeling of such data and identify synergistic phase interactions. MSPF is an interpretable machine learning algorithm that couples phase mapping via Deep Reasoning Networks (DRNets) to matrix factorization-based modeling of the representative properties of each phase in a dataset. MSPF is demonstrated for Bi–Cu–V oxide photoanodes for solar fuel generation, which contains 25 different phase combinations and correspondingly exhibits complex composition-structure-photoactivity relationships. Comparing the measured photoactivity to a learned model for non-interacting phases, synergistic phase interactions are identified to guide further photoactivity optimization and understanding. MSPF identifies synergistic interactions of a BiVO4-like phase with both Cu2V2O7-like and CuV2O6-like phases, creating avenues for understanding complex photoelectrocatalysts.

Abstract Background Resistance to standard therapy is a major reason for the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Developing novel therapy to overcome PDAC drug-resistance is urgently needed. CRABP-II was highly expressed in all PDAC but not expressed in normal pancreatic tissues and chronic pancreatitis. CRABP-II was shown to promote PDAC migration and metastasis while its potential role in promoting PDAC drug-resistance was not known. Methods A paired cohort of human primary and relapsing PDAC tissues was assessed for CRABP-II expression by immunohistochemistry. CRISPR/cas9 gene editing was used to establish CRABP-II knockout cell lines and MTT assays were performed to assess gemcitabine sensitivity in vitro. Cleaved caspase-3/PARP blots and Annexin V staining were conducted to detect cell apoptosis. Gene expression microarray, Q-PCR, western blots, Co-IP and RNA-IP were used to study the molecular function of CRABP-II. Sucrose gradient ultracentrifugation was applied to isolate lipid rafts and LC–MS-MS was used to assess cholesterol content. Both subcutaneous CDX models and orthotopic PDX models were established to examine the efficacy of SNIPER-11 and the synergistic effect between SNIPER-11 and gemcitabine in vivo. Results A higher expression of CRABP-II was found in relapsing PDAC tissue and was associated with poor prognosis. Gemcitabine-resistant cell lines exhibited increased level of CRABP-II, while CRABP-II knockout resensitized PDAC cells to gemcitabine. Mechanistically, aberrant expression of CRABP-II increased the stability of SREBP-1c mRNA through cooperation with HuR and upregulated the downstream genes of SREBP-1c to favor cholesterol uptake and accumulation in lipid rafts. Increased lipid raft cholesterol accumulation facilitated ATK survival signaling and PDAC drug resistance. The small compound SNIPER-11 treatment effectively induced CRABP-II protein degradation, induced apoptosis, and suppressed tumor growth. Combination of SNIPER-11 and gemcitabine significantly reduced the lipid raft cholesterol content in CDX/PDX and profoundly inhibited tumor progression. Conclusions These findings identified CRABP-II as a novel regulator of cholesterol metabolism and suggested that CRABP-II is a selective target for overcoming PDAC drug resistance.

Abstract Pear (Pyrus spp.) is one of the most consumed fruits in China, but the pear production has to confront the growing threat from fatal diseases. In this study, we report two incidences of stem canker and twig dieback disease on pear plants, which led to death of pear seedlings (approximately 10% of total plants) in Guangxi and Jiangsu provinces. Using a combination of morphological and molecular diagnoses, along with pathogenicity test, the causal agent of the disease in these two locations was identified to be the fungus Neofusicoccum parvum. However, the isolates were divided into two clades: CY-2 isolate and other four isolates including ZL-4, BM-9, BM-10 and BM-12 might split into two groups of N. parvum. Two representative isolates (CY-2 and ZL-4) were selected for further investigation. We observed that the optimal temperature for in vitro infection on pear trees of these two isolates was at round 25 °C. Both CY-2 and ZL-4 could infect different sand pear varieties and other horticultural plants in vitro, while CY-2 had a higher virulence on several pear varieties including Nanyue, Lvyun, Qiushui and Ningmenghuang. Furthermore, the efficacy of fungicides against these two isolates was evaluated, and carbendazim and flusilazole were found to be the most effective fungicides in inhibiting the growth of these fungal pathogens. Taken together, these findings redefine the N. parvum species and provide potential strategies for the future management of this disease.

The limitations of current medications for treating rheumatoid arthritis (RA) emphasize the urgent need for the development of new drugs. This study aimed to investigate the potential anti-RA mechanism of amygdalin using tandem mass tag (TMT)-based quantitative proteomics technology. First, the anti-RA activity of amygdalin was evaluated in a Complete Freund’s adjuvant (CFA)-induced rat model. Then, the roles and importance of proteins in the extracted rat joint tissue were evaluated using TMT-based quantitative proteomics technology. A bioinformatics analysis was used to analyze differentially abundant proteins (DAPs). A proteomics analysis identified 297 DAPs in the amygdalin group compared with the model group, of which 53 upregulated proteins and 51 downregulated proteins showed opposite regulatory trends to the DAPs produced after modeling. According to enrichment analyses of the DAPs, the signaling pathways with a high correlation degree were determined to be the complement and coagulation cascades. Furthermore, western blotting and molecular docking were used to further validate the key node proteins, e.g., complement C1s subcomponent (C1s), component C3 (C3) and kininogen 1 (Kng1). These results suggest that amygdalin may be a promising agent for treating RA by regulating the complement and coagulation cascades.

Summary: Fibrosis is a prominent pathological feature of skeletal muscle in Duchenne muscular dystrophy (DMD). The commonly used disease mouse model, mdx5cv, displays progressive fibrosis in the diaphragm but not limb muscles. We use single-cell RNA sequencing to determine the cellular expression of the genes involved in extracellular matrix (ECM) production and degradation in the mdx5cv diaphragm and quadriceps. We find that fibro/adipogenic progenitors (FAPs) are not only the primary source of ECM but also the predominant cells that express important ECM regulatory genes, including Ccn2, Ltbp4, Mmp2, Mmp14, Timp1, Timp2, and Loxs. The effector and regulatory functions are exerted by diverse FAP clusters which are different between diaphragm and quadriceps, indicating their activation by different tissue microenvironments. FAPs are more abundant in diaphragm than in quadriceps. Our findings suggest that the development of anti-fibrotic therapy for DMD should target not only the ECM production but also the pro-fibrogenic regulatory functions of FAPs.

Objective: This study aimed to address the status, role, and mechanism of sympathetic nerve infiltration in the progression of stomach adenocarcinoma (STAD). Methods: Sympathetic nerve and its neurotransmitter NE, β-ARs, and associated signaling molecules in the STAD tissues and the adjacent tissues from 46 STAD patients were examined using immunostaining, HPLC, and western blotting. The effects and mechanisms of β2-AR activation on the proliferation, migration and invasion of AGS and SGC-7901 gastric cancer (GC) cell lines were examined using CCK-8, transwell, and western blotting assays. Correlations between genes and STAD survival were analyzed using bioinformatics. Results: Striking sympathetic nerve infiltration, elevations of NGF, TrkA, GAP43, TH, S100, NE, β2-AR, YKL-40, syndecan-1, MMP9, CD206, and CD31 were observed in the STAD tissues compared to the adjacent tissues. Activation of β2-AR in the two GC cell lines significantly amplified the expressions of NGF, YKL-40, MMP9, syndecan-1, p-STAT3 and p-ERK, and increased GC cell proliferation, migration and invasion. Bioinformatic analyses revealed positive correlations of NGF, β2-AR, syndecan-1, and macrophage infiltration, respectively, with low survival of STAD, of β2-AR respectively with STAT3, ERK1/2 (MAPK1/3), YKL-40, MMP9, and syndecan-1, and of YKL-40 with MMP9. Conclusion: Sympathetic nerves significantly infiltrated into human STAD tissues as a result of high NGF and TrkA expressions; elevated NE led to overactivation of β2-AR-STAT3/ERK-YKL-40 signaling pathway, and finally caused cancer cell growth and invasion, M2 macrophage infiltration, angiogenesis, matrix degradation and STAD metastasis and progression.

Plum (Prunus salicina Lindl.) is one of the most widely cultivated and important fruit trees in temperate and cold regions. Fruit color is a significant trait relating to fruit quality in plum. However, its development mechanism has not been studied from the aspects of transcriptional regulation and metabolomic progress. To reveal the mechanism of fruit color developments in plums, we selected the fruits of two plum cultivars, ‘Changli84’ (Ch84, red fruit) and ‘Dahuangganhe’ (D, yellow fruit) as plant materials for transcriptome sequencing and metabolomic analysis were performed. Based on the data of transcriptome and metabolome at three fruit developmental stages, young fruit stage, color-change stage, and maturation stage, we identified 2,492 differentially expressed genes (DEGs) and 54 differential metabolites (DMs). The KEGG analysis indicated that “Flavonoid biosynthesis” was significantly enriched during three fruit development stages. Some DEGs in the “Flavonoid biosynthesis” pathway, had opposite trends between Ch84 and D, including chalcone synthase (CHS), dihydroflavonol 4-reductase (DFR) and flavonol synthase (FLS). Also, the genes encoding MYB–bHLH–WD (MBW) protein complexes, especially MYBs and bHLHs, showed a close relationship with plum fruit color. In the current study, DMs like procyanidin B1, cyanidin 3-glucoside, and cyanidin-3-O-alpha-arabinopyranoside were key pigments (or precursors), while the carotene and carotenoids did not show key relationships with fruit color. In conclusion, the anthocyanins dominate the color change of plum fruit. Carotenes and carotenoids might be related to the color of plum fruit, but do not play a dominate role.

Ovarian cancer is among the most common malignant tumors in gynecology and is characterized by insidious onset, poor differentiation, high malignancy, and a high recurrence rate. Numerous studies have shown that poly ADP-ribose polymerase (PARP) inhibitors can improve progression-free survival (PFS) in patients with BRCA-mutated ovarian cancer. With the widespread use of BRCA mutation and PARP inhibitor (PARPi) combination therapy, the side effects associated with BRCA mutation and PARPi have garnered attention worldwide. Mutations in the BRCA gene increase KEAP1-NRF2 ubiquitination and reduce Nrf2 content and cellular antioxidant capacity, which subsequently produces side effects such as cardiovascular endothelial damage and atherosclerosis. PARPi has hematologic toxicity, producing thrombocytopenia, fatigue, nausea, and vomiting. These side effects not only reduce patients’ quality of life, but also affect their survival. Studies have shown that natural phytochemicals, a class of compounds with antitumor potential, can effectively prevent and treat the side effects of chemotherapy. Herein, we reviewed the role of natural phytochemicals in disease prevention and treatment in recent years, including sulforaphane, lycopene, catechin, and curcumin, and found that these phytochemicals have significant alleviating effects on atherosclerosis, nausea, and vomiting. Moreover, these mechanisms of action significantly correlated with the side-effect-producing mechanisms of BRCA mutations and PARPi. In conclusion, natural phytochemicals may be effective in alleviating the side effects of BRCA mutant ovarian cancer cells and PARP inhibitors.

Background: After anterior cruciate ligament reconstruction, some patients are not recommended to return to high-level physical activity because they fail to pass return-to-sports tests. The kinematic difference between these patients and those who pass the return-to-sports tests is unclear.Methods: Eighty-two patients who received anatomic single-bundle anterior cruciate ligament (ACL) reconstruction for unilateral ACL injury underwent return-to-sport tests during a hospital visit at a minimum of 9 months (9–11 months) of follow-up. Fifteen patients who passed the return-to-sports tests (RTS group) and fifteen patients who did not (NRTS group) were randomly selected to perform a treadmill walk under dual-fluoroscopic imaging system surveillance for a 6 degrees of freedom kinematic evaluation.Results: Of the 82 patients, 53 passed the return-to-sports tests 9 months after surgery, with a return-to-sports rate of 64.6%. In the stance phase, the NRTS group had a larger anterior tibial translation (1.00 ± 0.03 mm vs. 0.76 ± 0.03 mm, p = 0.001), a larger lateral tibial movement (1.61 ± 0.05 mm vs. 0.77 ± 0.05 mm, p < 0.001), a larger distal tibial displacement (−3.09 ± 0.05 mm vs. −2.69 ± 0.05 mm, p < 0.001), a smaller knee flexion angle (6.72 ± 0.07° vs. 8.34 ± 0.07°, p < 0.001), a larger varus angle (−0.40 ± 0.03°VS. -0.01 ± 0.03°, p < 0.001) and a larger external rotation angle (1.80 ± 0.05° vs. 1.77 ± 0.05°, p < 0.001) than the RTS group. The maximum anterior tibial translation of the NRTS group is also larger than that of the RTS group (3.64 ± 0.42 mm vs. 3.03 ± 0.59 mm, p = 0.003).Conclusion: Compared with patients passing RTS tests, those who fail to pass show significant anterior, lateral, and rotational instability; knee laxity; and reduced flexion angle of the knee in the support phase during walking, which may be the possible factors hindering a return to sports.

It is generally believed that the interaction between acid precipitation and asphalt has an effect on the performance of drainage asphalt pavement, but studies on the interface behavior characteristics from microscopic analysis are rare. Therefore, molecular dynamics (MD) was used to simulate the interfacial transition zone of precipitation (neutral and acid) and asphalt in the study, and the interfacial behavior characteristics of precipitation on asphalt surface were microscopically analyzed. Additionally, the composition of acid precipitation was configured in the laboratory, and the contact angles of precipitation solutions (SO42− and NO3−) on asphalt surface also verified the interface behavior characteristics between acid precipitation and asphalt. The results showed that the interaction of acid precipitation and asphalt is stronger than that of neutral precipitation, which makes it more difficult to remove from the surface of drainage asphalt pavement. With the increase of service temperature for drainage asphalt pavement, the interaction energy increases. Under the coupling effect of acid precipitation and low service temperature, water damage to the drainage asphalt pavement is more easily induced. The results revealed the micro-effect of acid precipitation and service temperature on drainage efficiency of an asphalt surface, which has certain theoretical significance and practical value for the application and exploration of drainage asphalt pavement. HIGHLIGHTS Interaction energy between acid precipitation and asphalt is stronger.; As the service temperature rises, the interface behavior of precipitation on an asphalt surface becomes more visibly active.; The coupling of acid precipitation and low temperature will further increase the influence of drainage asphalt pavement.; Acid precipitation has a smaller contact angle, that is, better wettability.;

Abstract Purpose To investigate the frailty status in Chinese cancer patients through establishing a novel prediction algorithm. Methods The percentage of frailty in various age groups, locations, and tumor types in Chinese cancer patients was investigated. The prediction capacity of frailty on mortality of Chinese cancer patients was analysed by the frailty index composing of routine laboratory data (FI‐LAB) accessible from a blood test and calculated as the ratio of abnormal factors to 22 total variables. The establishment of a novel algorithm, MCP (mortality of cancer patients), to predict the 5‐year mortality in Chinese cancer patients was accomplished and the algorithm's prediction capacity was tested in the training and validation sets using receiver operating characteristic (ROC) analysis. Results We found that the risk of death in cancer patients can be successfully identified through FI‐LAB. The univariable and multivariable Cox regression were used to evaluate the effect of frailty on death. In the 5‐year follow‐up, 20.6% of the 2959 participants (age = 55.8 ± 11.7 years; 43.5% female) died, while the mean FI‐LAB score in baseline was 0.23 (standard deviation = 0.13; range = 0–0.73). Frailty (after adjusting for gender, age, and other confounders) directly correlated with an increased risk of death, hazard ratio of 12.67 (95% confidence interval [CI]: 7.19, 22.31), compared to those without frailty. In addition, the MCP algorithm (MCP) = 3.678 × FI‐LAB + 1.575 × sex + 1.779 × first tumor node metastasis staging, presented an area under the ROC (AUC) of 0.691 (95% CI: 0.656–0.726) and 0.648 (95% CI: 0.613–0.684) in the training and validation sets, respectively. Conclusion Frailty as defined by FI‐LAB was common and indicated a significant death risk in cancer patients. Our novel developed algorithm MCP had a passable prediction capacity on 5‐year MCP.

BackgroundPopulation aging accompanied by multimorbidity imposes a great burden on households and the healthcare system. This study aimed to determine the incidence and determinants of catastrophic health expenditure (CHE) in the households of old people with multimorbidity in China.MethodsData were obtained from the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2018, with 3,511 old people (≥60 years) with multimorbidity responding to the survey on behalf of their households. CHE was identified using two thresholds: ≥10% of out-of-pocket (OOP) health spending in total household expenditure (THE) and ≥40% of OOP health spending in household capacity to pay (CTP) measured by non-food household expenditure. Logistic regression models were established to identify the individual and household characteristics associated with CHE incidence.ResultsThe median values of THE, OOP health spending, and CTP reached 19,900, 1,500, and 10,520 Yuan, respectively. The CHE incidence reached 31.5% using the ≥40% CTP threshold and 45.6% using the ≥10% THE threshold. It increased by the number of chronic conditions reported by the respondents (aOR = 1.293–1.855, p < 0.05) and decreased with increasing household economic status (aOR = 1.622–4.595 relative the highest quartile, p < 0.001). Hospital admissions over the past year (aOR = 6.707, 95% CI: 5.186 to 8.674) and outpatient visits over the past month (aOR = 4.891, 95% CI: 3.822 to 6.259) of the respondents were the strongest predictors of CHE incidence. The respondents who were male (aOR = 1.266, 95% CI: 1.054 to 1.521), married (OR = 1.502, 95% CI: 1.211 to 1.862), older than 70 years (aOR = 1.288–1.458 relative to 60–69 years, p < 0.05), completed primary (aOR = 1.328 relative to illiterate, 95% CI: 1.079 to 1.635) or secondary school education (aOR = 1.305 relative to illiterate, 95% CI: 1.002 to 1.701), lived in a small (≤2 members) household (aOR = 2.207, 95% CI: 1.825 to 2.669), and resided in the northeast region (aOR = 1.935 relative to eastern, 95% CI: 1.396 to 2.682) were more likely to incur CHE.ConclusionMultimorbidity is a significant risk of CHE. Household CHE incidence increases with the number of reported chronic conditions. Socioeconomic and regional disparities in CHE incidence persist in China.

Background: There are currently no well-established criteria to guide return to sports (RTS) after anterior cruciate ligament reconstruction (ACLR). In this study, a new test battery consisting of subjective and objective tests, especially multiplanar knee kinematics assessment, was developed to aid RTS decision making after ACLR.Methods: This study was conducted with 30 patients who were assessed a mean of 9.2 ± 0.5 months after ACLR. All patients underwent complete evaluations of both lower limbs with four objective assessments [isokinetic, hop, knee laxity, and 6–degree of freedom (6DOF, angle: flexion-extension, varus-valgus, internal-external rotation; translation: anteroposterior, proximodistal, mediolateral) knee kinematics tests] and two subjective assessments [International Knee Documentation Committee (IKDC) and Anterior Cruciate Ligament Return to Sport after Injury (ACL-RSI) questionnaires]. Limb symmetry indices (LSIs) of knee strength, hop distance, and range of motion (ROM) of knee kinematics were calculated. LSI ≥90%, IKDC scale score within the 15th percentile for healthy adults, and ACL-RSI score >56 were defined as RTS criteria.Results: Significant differences between affected and contralateral knees were observed in the quadriceps strength (p < 0.001), hamstring strength (p = 0.001), single hop distance (p < 0.001), triple hop distance (p < 0.001), and rotational ROM (p = 0.01). Only four patients fulfilled the overall RTS criteria. The percentages of patients fulfilling individual criteria were: quadriceps strength, 40%; hamstring strength, 40%; single hop distance, 30%; triple hop distance, 36.7%; knee ligament laxity, 80%; flexion-extension, 23.3%; varus-valgus rotation, 20%; internal-external rotation, 66.7%; anteroposterior translation, 20%; proximodistal translation, 33.3%; mediolateral translation, 26.7%; IKDC scale score, 53.3%; and ACL-RSI score, 33.3%.Conclusion: At an average of 9 months after ACLR, objectively and subjectively measured knee functional performance was generally unsatisfactory especially the recovery of knee kinematics, which is an important prerequisite for RTS.

Mental health is a kind of emotional state, a good psychological state can have a positive impact on a person, physical exercise can have a positive impact on the psychological state of college students, prevent the generation of negative emotions, improve the bad emotional state, and then promote the mental health of college students. Health is an inevitable requirement to promote the all-round development of people and a basic condition for economic and social development. Health education should be incorporated into the national education system to promote the national health of the people through sports. Young people are the main force and backbone of national and social development. In order to realize the Chinese dream of great rejuvenation, we must attach importance to the development of young people and the physical and mental health of young people. In the process of compulsory education, middle school and high school period is a key stage in the gradual formation and development of students' psychology and body, but due to the large audience of China's education, the competition is more intense, which inevitably causes a lot of students to focus on exam-oriented education and neglect physical health, especially in recent years, the mental health issues of increasing concern. Through the research situation of mental health in China and the concept of mental health quality, this paper analyzes the problems of sports and mental health, and puts forward some corresponding suggestions for the problems, which has reference significance for promoting students' mental health.

Bone age is the chronological age of human bones, which serves as a key indicator of the maturity of bone development and can more objectively reflect the extent of human growth and development. The prevalent viewpoint and research development direction now favor the employment of deep learning-based bone age detection algorithms to determine bone age. Although bone age detection accuracy has increased when compared to more established methods, more work needs to be conducted to raise it because bone age detection is primarily used in clinical medicine, forensic identification, and other critical and rigorous fields. Due to the symmetry of human hand bones, bone age detection can be performed on either the left hand or the right hand, and the results are the same. In other words, the bone age detection results of both hands are universal. In this regard, the left hand is chosen as the target of bone age detection in this paper. To accomplish this, the You Only Look Once-v5 (YOLOv5) and Residual Network-34 (ResNet34) integration techniques are combined in this paper to create an innovative bone age detection model (YARN), which is then combined with the RUS-CHN scoring method that applies to Chinese adolescent children to comprehensively assess bone age at multiple levels. In this study, the images in the hand bone dataset are first preprocessed with number enhancement, then YOLOv5 is used to train the hand bone dataset to identify and filter out the main 13 joints in the hand bone, and finally, ResNet34 is used to complete the classification of local joints and achieve the determination of the developmental level of the detected region, followed by the calculation of the bone age by combining with the RUS-CHN method. The bone age detection model based on YOLOv5 and ResNet34 can significantly improve the accuracy and efficiency of bone age detection, and the model has significant advantages in the deep feature extraction of key regions of hand bone joints, which can efficiently complete the task of bone age detection. This was discovered through experiments on the public dataset of Flying Paddle AI Studio.

Abstract Background A long-term of peritoneal dialysis (PD) using a hypertonic PD solution (PDS) leads to patient’s peritoneal membrane (PM) injury, resulting in ultrafiltration failure (UFF) and PD drop-out. Our previous study shows that PD effluent-derived mesenchymal stromal cells (pMSCs) prevent the PM injury in normal rats after repeated exposure of the peritoneal cavity to a PDS. This study was designed to compare the cytoprotection between pMSCs and umbilical cord-derived MSCs (UC-MSCs) in the treatment of both PM and kidney injury in uremic rats with chronic PD. Methods 5/6 nephrectomized (5/6Nx) Sprague Dawley rats were intraperitoneally (IP) injected Dianeal (4.25% dextrose, 10 mL/rat/day) and were treated with pMSCs or umbilical cord (UC)-MSCs (approximately 2 × 106/rat/week, IP). Ultrafiltration was determined by IP injection of 30 mL of Dianeal (4.25% dextrose) with 1.5-h dewell time, and kidney failure by serum creatinine (SCr) and blood urea nitrogen (BUN). The structure of the PM and kidneys was assessed using histology. Gene expression was examined using quantitative reverse transcription PCR, and protein levels using flow cytometric and Western blot analyses. Results We showed a slight difference in the morphology between pMSCs and UC-MSCs in plastic dishes, and significantly higher expression levels of stemness-related genes (NANOG, OCT4, SOX2, CCNA2, RAD21, and EXO1) and MSCs surface markers (CD29, CD44, CD90 and CD105) in UC-MSCs than those in pMSCs, but no difference in the differentiation to chondrocytes, osteocytes or adipocytes. pMSC treatment was more effective than UC-MSCs in the protection of the MP and remnant kidneys in 5/6Nx rats from PDS-induced injury, which was associated with higher resistance of pMSCs than UC-MSCs to uremic toxins in culture, and more reduction of peritoneal mesothelial cell death by the secretome from pMSCs than from UC-MSCs in response to PDS exposure. The secretome from both pMSCs and UC-MSCs similarly inactivated NOS2 in activated THP1 cells. Conclusions As compared to UC-MSCs, pMSCs may more potently prevent PDS-induced PM and remnant kidney injury in this uremic rat model of chronic PD, suggesting that autotransplantation of ex vivo-expanded pMSCs may become a promising therapy for UFF and deterioration of remnant kidney function in PD patients.

Abstract Crotonylation of proteins is a newly found type of post-translational modifications (PTMs) which occurs leadingly on the lysine residue, namely, lysine crotonylation (Kcr). Kcr is conserved and is regulated by a series of enzymes and co-enzymes including lysine crotonyltransferase (writer), lysine decrotonylase (eraser), certain YEATS proteins (reader), and crotonyl-coenzyme A (donor). Histone Kcr has been substantially studied since 2011, but the Kcr of non-histone proteins is just an emerging field since its finding in 2017. Recent advances in the identification and quantification of non-histone protein Kcr by mass spectrometry have increased our understanding of Kcr. In this review, we summarized the main proteomic characteristics of non-histone protein Kcr and discussed its biological functions, including gene transcription, DNA damage response, enzymes regulation, metabolic pathways, cell cycle, and localization of heterochromatin in cells. We further proposed the performance of non-histone protein Kcr in diseases and the prospect of Kcr manipulators as potential therapeutic candidates in the diseases.

Skeletal muscle is essential to physical activity and energy metabolism. Maintaining intact functions of skeletal muscle is crucial to health and wellbeing. Evolutionarily, skeletal muscle has developed a remarkable capacity to maintain homeostasis and to regenerate after injury, which indispensably relies on the resident muscle stem cells, satellite cells. Satellite cells are largely quiescent in the homeostatic steady state. They are activated in response to muscle injury. Activated satellite cells proliferate and differentiate into myoblasts. Myoblasts fuse to form myotubes which further grow and differentiate into mature myofibers. This process is tightly regulated by muscle microenvironment that consists of multiple cellular and molecular components, including macrophages. Present in both homeostatic and injured muscles, macrophages contain heterogeneous functional subtypes that play diverse roles in maintaining homeostasis and promoting injury repair. The spatial-temporal presence of different functional subtypes of macrophages and their interactions with myogenic cells are vital to the proper regeneration of skeletal muscle after injury. However, this well-coordinated process is often disrupted in a chronic muscle disease, such as muscular dystrophy, leading to asynchronous activation and differentiation of satellite cells and aberrant muscle regeneration. Understanding the precise cellular and molecular processes regulating interactions between macrophages and myogenic cells is critical to the development of therapeutic manipulation of macrophages to promote injury repair. Here, we review the current knowledge of the many roles played by macrophages in the regulation of myogenic cells in homeostatic, regenerating, and dystrophic skeletal muscles.