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Abstract Background Nutrition and its associated inflammation have been acknowledged as vital factors in the etiopathogenesis of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. The nutritional risk index (NRI) has been widely recognized as a valid indicator of nutritional status in several diseases, including osteoporosis and cardiovascular disease. However, the role of NRI in NAFLD and liver fibrosis remains unclear. Methods Participants were selected from the National Health and Nutrition Examination Survey data for the 2017–2018 cycle. Association between NRI and both NAFLD and liver fibrosis was evaluated using multiple logistic regression and restricted cubic spline (RCS) analysis. Mediation analysis was employed to assess the influence of inflammation on the association between NRI and both NAFLD and liver fibrosis. Results Compared to their respective control groups, individuals with NAFLD and liver fibrosis exhibited higher NRI levels. Multiple logistic regression analyses indicated that NRI was positively associated with the odds of NAFLD and liver fibrosis across both continuous scales and quantile groups, with adjustments for relevant covariables. The RCS model demonstrated a dose-response effect between NRI and the odds of NAFLD, but not with liver fibrosis. Receiver operating characteristic (ROC) analysis revealed the area under the ROC curves of 0.798 and 0.775 for NAFLD and liver fibrosis, respectively. Mediation analysis showed that inflammation accounted for 3.139% of the effect of NRI on the odds of NAFLD, suggesting inflammation might partially mediate the impact of NRI on NAFLD. Conclusions Our findings indicate that NRI may serve as a potential associated marker for these liver diseases, underscoring the importance of nutritional status in their etiopathogenesis.

ObjectivesTo explore the effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) on motor function and cortical excitability in stroke patients with different motor evoked potential (MEP) status.MethodsA total of 80 stroke patients were enrolled in this randomized controlled trial and divided into two groups according to MEP status (− or +) of lesioned hemisphere. Then, each group was randomly assigned to receive either active or sham LF-rTMS. In addition to conventional rehabilitation, all participants received 20 sessions of rTMS at 1 Hz frequency through the active or the sham coil over 4 weeks. Fugl-Meyer Assessment (FMA), National Institutes of Health Stroke Scale (NIHSS), Shoulder Abduction Finger Extension (SAFE) and Barthel Index (BI), bilateral resting motor threshold (rMT), amplitude of Motor evoked potential (MEP) and Central Motor Conduction Time (CMCT), and Interhemispheric asymmetry (IHA) were blindly assessed at baseline, 4 weeks and 8 weeks after treatment, respectively.ResultsAt 4 weeks after intervention, FMA and NIHSS changed scores in 1 Hz MEP(+) group were significantly higher than those in the other three groups (p

This manuscript addresses the issue of electromagnetic radiation interference experienced by secondary equipment in ultra-high voltage (UHV) fixed series capacitors (FSCs) under electromagnetic transient overvoltage conditions, which cannot be easily determined. To tackle this, a simulation and analysis method for the electromagnetic interference characteristics of secondary equipment is proposed. First, a primary system simulation model of UHV FSC is established, including modeling the platform’s multi-conductor system. The electromagnetic transient overvoltage signals between the low-voltage busbar and the high-potential platform are then simulated and analyzed under two conditions: spark gap triggering and disconnector operation. Next, a finite element model of secondary equipment is created to simulate and analyze the electric field distribution of different materials in the area of the measuring box. The shielding effectiveness of the measuring box is calculated using the overvoltage signals at the measuring box location as excitation. This method allows for the simulation of the electric field distribution in the measuring box area for different materials and calculates the shielding efficiency of the measuring box. It effectively simulates the complex electromagnetic environment of secondary equipment, assesses the electromagnetic shielding efficiency of the measuring box, and provides a theoretical basis for analyzing and improving the anti-interference characteristics of the measuring box.

Treatment of osteochondral (OC) defects is still an immense challenge in clinic due to lack of satisfactory strategy to simultaneously regenerate both cartilage and subchondral bone. Herein, we propose an effective bottom-up strategy by developing a type of multifunctional chitosan-based nanocomposite microgels as the building blocks to repair OC defects. The microgels are biocompatible, and biodegradable, and have a hierarchical nanofibrous structure, mimicking the structural feature of extracellular matrix (ECM) to facilitate cell attachment and proliferation. Additionally, β-tricalcium phosphate (β-TCP) nanoparticles are incorporated in the microgels not only to promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), but also to facilitate the loading of transforming growth factor beta 1 (TGF-β1). For reconstructing OC defects, pure microgels are implanted at the bottom layer of the OC defects in rat knee joints to promote osteogenesis, while the microgels loaded with TGF-β1 are implanted at the top layer of the OC defects to promote cartilage regeneration. This modular microgel system results in simultaneous regeneration of cartilage and subchondral bone in OC defects, which is expected as a promising way for repairing other complex tissue defects in the field of tissue engineering.

This study aims to increase our understanding regarding the use of rituals as the prevention and management strategies for the external consequences resulting from sexual harassment in the workplace during the COVID-19 crisis. We conducted a qualitative study through semi-structured interviews (N = 30) with employees in five hospitals and analyzed the data with a grounded theory approach. The results indicated that rituals could positively influence reputation repair and legitimacy construction. Moreover, interaction patterns between organizations and stakeholders mediated the relationships between rituals and prevention and management results heterogeneously. Managerial perceptions, ritual factors and cultural factors influence rituals to achieve more effective results in terms of prevention and management. By presenting a process model illustrating rituals’ unique capacity to prevent and manage the threats of workplace sexual harassment, we contribute to the literature on workplace sexual harassment and rituals in three ways. First, we extend the workplace sexual harassment literature by exploring prevention and management strategies for external consequence/reputation threats. Second, we present a process model to illustrate how rituals impact the results of sexual harassment prevention and management strategies. Third, we illustrate the mediating and moderating factors and their contributions toward developing better rituals that function in such prevention and management strategies.

Abstract The second polar body (PB2) transfer in assisted reproductive technology is regarded as the most promising mitochondrial replacement scheme for preventing the mitochondrial disease inheritance owing to its less mitochondrial carryover and stronger operability. However, the mitochondrial carryover was still detectable in the reconstructed oocyte in conventional second polar body transfer scheme. Moreover, the delayed operating time would increase the second polar body DNA damage. In this study, we established a spindle‐protrusion‐retained second polar body separation technique, which allowed us to perform earlier second polar body transfer to avoid DNA damage accumulation. We could also locate the fusion site after the transfer through the spindle protrusion. Then, we further eliminated the mitochondrial carryover in the reconstructed oocytes through a physically based residue removal method. The results showed that our scheme could produce a nearly normal proportion of normal‐karyotype blastocysts with further reduced mitochondrial carryover, both in mice and humans. Additionally, we also obtained mouse embryonic stem cells and healthy live‐born mice with almost undetectable mitochondrial carryover. These findings indicate that our improvement in the second polar body transfer is conducive to the development and further mitochondria carryover elimination of reconstructed embryos, which provides a valuable choice for future clinical applications of mitochondrial replacement.

Hypoxia induces mitochondrial clearance and autophagy, although the upstream mechanisms are not well defined. Here, the authors identify that oxygen-sensitive methylation of the key autophagy regulator ULK1 promotes ULK1 activation and subsequent autophagosome formation and mitochondrial clearance.

Abstract Exposure to radiation causes DNA damage; hence, continuous surveillance and timely DNA repair are important for genome stability. Epigenetic modifications alter the chromatin architecture, thereby affecting the efficiency of DNA repair. However, how epigenetic modifiers coordinate with the DNA repair machinery to modulate cellular radiosensitivity is relatively unknown. Here, we report that loss of the demethylase ribosomal oxygenase 1 (RIOX1) restores cell proliferation and reduces cell death after exposure to ionizing radiation. Furthermore, RIOX1 depletion enhances homologous recombination (HR) repair but not nonhomologous end-joining (NHEJ) repair in irradiated bone marrow cells and oral mucosal epithelial cells. Mechanistic study demonstrates that RIOX1 removes monomethylation at K491 of cyclic GMP-AMP synthase (cGAS) to release cGAS from its interaction with the methyl-lysine reader protein SAGA complex-associated factor 29 (SGF29), which subsequently enables cGAS to interact with poly(ADP-ribosyl)ated poly(ADP-ribose) polymerase 1 (PARP1) at DNA break sites, thereby blocking PARP1-mediated recruitment of Timeless. High expression of RIOX1 maintains cGAS K491me at a low level, which impedes HR repair and reduces cellular tolerance to ionizing radiation. This study highlights a novel RIOX1-dependent mechanism involved in the non-immune function of cGAS that is essential for the regulation of ionizing radiation-elicited HR repair.

The gut microbiota, as a ‘new organ’ of humans, has been identified to affect many biological processes, including immunity, inflammatory response, gut-brain neural circuits, and energy metabolism. Profound dysbiosis of the gut microbiome could change the metabolic pattern, aggravate systemic inflammation and insulin resistance, and exacerbate metabolic disturbance and the progression of type 2 diabetes (T2D). The aim of this review is to focus on the potential roles and functional mechanisms of gut microbiota in the antidiabetic therapy. In general, antidiabetic drugs (α-glucosidase inhibitor, biguanides, incretin-based agents, and traditional Chinese medicine) induce the alteration of microbial diversity and composition, and the levels of bacterial component and derived metabolites, such as lipopolysaccharide (LPS), short chain fatty acids (SCFAs), bile acids and indoles. The altered microbial metabolites are involved in the regulation of gut barrier, inflammation response, insulin resistance and glucose homeostasis. Furthermore, we summarize the new strategies for antidiabetic treatment based on microbial regulation, such as pro/prebiotics administration and fecal microbiota transplantation, and discuss the need for more basic and clinical researches to evaluate the feasibility and efficacy of the new therapies for diabetes.

Broadband dual‐comb spectroscopy has attracted increasing interests due to its unique advantages in high spectral resolution, fast detection, and so on. Although the dual‐comb technique is relatively mature in the infrared wavelengths, it is, currently, not commercially capable of practical applications in the terahertz regime due to the lack of high‐performance broadband terahertz dual‐comb sources. In the terahertz frequency range, the electrically pumped quantum cascade laser (QCL) is a suitable candidate for the dual‐comb operation. Although the resonant microwave injection locking is widely used to broaden the emission spectra of terahertz QCLs, it is challenging to be employed to obtain broadband dual‐comb sources that can fully exploit the laser gain bandwidth due to the large phase noise induced by the resonant injection and nonideal microwave circuits. Herein, an off‐resonant microwave injection to significantly broaden the dual‐comb bandwidth of a terahertz QCL dual‐comb source is used. The measured optical dual‐comb bandwidth is broadened from 147 GHz in free running to >450 GHz under the off‐resonant injection. By performing a numerical analysis based on a rate equation model, the broadband dual‐comb operation under the off‐resonant microwave injection can result from a wider lasing bandwidth and a higher degree of phase matching.

Radiation-induced oral mucositis is the most common complication for patients who receive head/neck radiotherapy. Nicotinamide adenine dinucleotide (NAD+) is vital for DNA damage repair under ionizing radiation, through functioning as either the substrate for protein poly(ADP-ribosyl)ation at DNA break sites or the cofactor for multiple DNA repair-related enzymes, which therefore can result in a significant consumption of cellular NAD+ during DNA repair. Mammalian cells produce NAD+ mainly by recycling nicotinamide via the salvage pathway, in which the rate-limiting step is governed by nicotinamide phosphoribosyltransferase (NAMPT). However, whether NAMPT is co-opted under ionizing radiation to timely fine-tune NAD+ homeostasis remains elusive. Here we show that ionizing radiation evokes NAMPT activation within 30 min without apparent changes in its protein expression. AMPK rapidly phosphorylates NAMPT at S314 under ionizing radiation, which reinforces the enzymatic activity of NAMPT by increasing NAMPT binding with its substrate phosphoribosyl pyrophosphate (PRPP). AMPK-mediated NAMPT S314 phosphorylation substantially restores NAD+ level in the irradiated cells and facilitates DNA repair and cell viability. Our findings demonstrate a new post-translational modification-based signalling route, by which cells can rapidly orchestrate NAD+ metabolism to support DNA repair, thereby highlighting NAMPT as a potential target for the prevention of ionizing radiation-induced injuries.

Abstract Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide, and with 354 864 new cases each year. Cancer metastasis, recurrence, and drug resistance are the main causes to cripples and deaths of OSCC patients. As potent growth factors, fibroblast growth factors (FGFs) are frequently susceptible to being hijacked by cancer cells. In this study, we show that FGF8 is upregulated in OSCC tissues and high FGF8 expression is related with a set of clinicopathologic parameters, including age, drinking, and survival time. FGF8 treatment enhances the invasive capability of OSCC cells. Lentivirus-based FGF8 expression promotes OSCC metastasis in a mouse lung metastasis model. Further, mechanistic study demonstrates that FGF8 induces epithelial–mesenchymal transition (EMT) in OSCC cells. These results highlight a pro-metastatic function of FGF8, and underscore the role of FGF8 in OSCC development.

Ecological carrying capacity (ECC) is a key indicator for assessing the sustainable development capacity of a region. A comprehensive assessment of regional ECC and the influencing factors has scientific and practical significance for promoting functional and sustainable regional development. The Driver-Pressure-State-Impact-Response-Management (DPSIRM) framwork and subjective-objective combination method were used to develop a framework to establish an ECC evaluation index system. In this study, six internal and six external factors from the perspectives of nature, topography, society, and landscape patterns were selected from the Dongliao River Basin (DRB) in the Jilin province, China. Geographically weighted regression, redundancy analysis, and multiple linear regression models were used to reveal the coupling relationships among the internal and external factors. The results showed that the ECC in the study area was spatially heterogeneous with higher ECC in the southeast and northwest areas of the DRB and lower ECC in the central of DRB had a low carrying capacity. ECC showed a gradual upward trend from 2005 to 2018, which was attributed to the implementation of the ecological environment protection policy in DRB. Primary internal factors that influenced the ECC were precipitation, temperature, altitude, and slope. Precipitation had a positive effect on ECC by influencing Shannon’s diversity and landscape shape, while temperature, altitude, and slope had a negative effect on ECC by affecting aggregation and patch density. The methods used herein and the presented results are instructive to sustainable development and ecological restoration in the DRB and other similar areas.

Background: Increasing evidence indicates that the gut microbiota contributes to the occurrence and development of metabolic diseases. However, little is known about the effects of commonly used antidiabetic agents on the gut microbiota. In this study, we investigated the roles of dipeptidyl peptidase-4 inhibitors (DPP-4i) and α-glucosidase inhibitor in modulating the gut microbiota. Methods: 16S-rDNA sequencing was performed to analyse the effects of DPP-4i and acarbose on the gut microbiota in mice fed a high-fat diet (HFD). Fecal microbiota transplantation (FMT) from type 2 diabetes patients to germ-free mice was performed to investigate the contribution of the altered microbiome to antidiabetic effects of the drugs. Fecal metabolomics was also analysed by untargeted and targeted GC–MS systems. Findings: Although DPP-4i and α-glucosidase inhibitor both altered the gut microbial composition, only the microbiome modulation of DPP-4i contributed to its hypoglycemic effect. Specifically, the changes of 68.6% genera induced by HFD were rescued by DPP-4i. FMT showed that the DPP-4i-altered microbiome improved glucose tolerance in colonized mice, while acarbose did not. Moreover, DPP-4i increased the abundance of Bacteroidetes, and also promoted a functional shift in the gut microbiome, especially increasing the production of succinate. Interpretation: Our findings demonstrate an important effect of DPP-4i on the gut microbiota, revealing a new hypoglycemic mechanism and an additional benefit of it. Furthermore, modulating the microbial composition, and the functional shift arising from changes in the microbiome, might be a potential strategy for improving glucose homeostasis. Fund: This work was supported by grants from the National Natural Science Foundation of China (No. 81700757, No. 81471039, No. 81700714 and No. 81770434), the National Key R&D Program of China (No. 2017YFC1309602, No. 2016YFC1101100, No. 2017YFD0500503 and No. 2017YFD0501001), and the Natural Science Foundation of Chongqing (No. cstc2014jcyjjq10006, No. cstc2016jcyjA0093 and No. cstc2016jcyjA0518). Keywords: DPP-4i, Gut microbiota, Glucose tolerance, GF mice

Objective: To investigate the correlation between the left arcuate fasciculus (AF) segments and acute/subacute post-stroke aphasia (PSA). Methods: Twenty-six patients underwent language assessment and MRI scanning. The integrity of the AF based on a three-segment model was evaluated using diffusion tensor imaging. All patients were classified into three groups according to the reconstruction of the left AF: completely reconstructed (group A, 8 cases), non-reconstructed (group B, 6 cases), and partially reconstructed (group C, 12 cases). The correlations and intergroup differences in language performance and diffusion indices were comprehensively estimated. Results: A correlation analyses showed that the lesion load of the language areas and diffusion indices on the left AF posterior and long segments was significantly related to some language subsets, respectively. When controlled lesion load was variable, significant correlations between diffusion indices on the posterior and long segments and comprehension, repetition, naming, and aphasia quotient were retained. Multiple comparison tests revealed intergroup differences in diffusion indices on the left AF posterior and long segments, as well as these language subsets. No significant correlation was found between the anterior segment and language performance. Conclusions: The integrity of the left AF segments, particularly the posterior segment, is crucial for the residual comprehension and repetition abilities in individuals with acute/subacute PSA, and lesion load in cortical language areas is an important factor that should be taken into account when illustrating the contributions of damage to special fiber tracts to language impairments.

Abstract While adult mammalian skeletal muscle is stable due to its post‐mitotic nature, muscle regeneration is still essential throughout life for maintaining functional fitness. During certain diseases, such as the modern pandemics of obesity and diabetes, the regeneration process becomes impaired, which leads to the loss of muscle function and contributes to the global burden of these diseases. However, the underlying mechanisms of the impairment are not well defined. Here, we identify mGPDH as a critical regulator of skeletal muscle regeneration. Specifically, it regulates myogenic markers and myoblast differentiation by controlling mitochondrial biogenesis via CaMKKβ/AMPK. mGPDH−/− attenuated skeletal muscle regeneration in vitro and in vivo, while mGPDH overexpression ameliorated dystrophic pathology in mdx mice. Moreover, in patients and animal models of obesity and diabetes, mGPDH expression in skeletal muscle was reduced, further suggesting a direct correlation between its abundance and muscular regeneration capability. Rescuing mGPDH expression in obese and diabetic mice led to a significant improvement in their muscle regeneration. Our study provides a potential therapeutic target for skeletal muscle regeneration impairment during obesity and diabetes.

Background. High levels of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) were associated with an increased risk of hyperglycemia and the onset of diabetes. This study is aimed at assessing circulating valine concentrations in subjects with type 2 diabetes (T2D) and in T2D patients and high-fat diet- (HFD-) fed mice treated with the hypoglycemic agent sitagliptin (Sit) and analyzing the association of valine concentrations with metabolic parameters. Methods. Metabolomics in HFD-fed mice were analyzed by gas chromatography-mass spectrometry (GC-MS) systems. Plasma valine concentrations were detected with a commercial kit in 53 subjects with normal glucose levels (n=19), newly diagnosed T2D (n=20), placebo-treated T2D (n=7), or Sit-treated T2D (n=7). Biochemical parameters were also assessed in all participants. Results. Sit treatment markedly changed the pattern of amino acid in HFD-fed mice, especially by reducing the level of the BCAA valine. Compared with the healthy controls, the plasma valine concentrations were significantly higher in the T2D patients (p

This study explores the effect of the overseas growth experiences of successors in family businesses on corporate risk-taking. We theorize that successors in family businesses, influenced by psychological characteristics imprinted during their overseas experiences, are more inclined to undertake risky strategic decisions. However, due to considerations related to social emotional wealth, family businesses may intervene in the successors’ risk-taking decisions. Therefore, family control may positively or negatively moderate the relationship between successors’ overseas growth experiences and corporate risk-taking. Our theoretical expectations are tested using a matched sample of Chinese-listed family firms from 2012 to 2021. With supportive empirical results, we contribute to the literature on risk-taking by This study explores the effect of the overseas growth experiences of successors in family businesses on corporate risk-taking by exploring the predecessors of corporate risk-taking and enriching SEW theory by bringing in the insights of imprinting theory. [ABSTRACT FROM AUTHOR]

The electrically-pumped terahertz quantum cascade laser (QCL) is characterized by high power emission, compact, broad frequency coverage, and so on, which shows abilities for frequency comb operations. Although free running QCLs can work as frequency combs by designing the laser structure with small group velocity dispersions and/or inserting mirrors to compensate laser intrinsic dispersions, the ideal comb operation can only be obtained by firmly locking the repetition frequency and carrier frequency of a laser. In this work, we have reported a repetition frequency locking of a terahertz QCL emitting around 4.2 THz. When the 6-mm-long laser is operated in continuous wave mode without any locking techniques, the repetition frequency is measured to be ~6.15 GHz with a linewidth of hundred kilohertz. Once a phase lock loop (PLL) is applied to dynamically control the drive current of the QCL, we have demonstrated a successful repetition frequency locking of the laser with a signal to noise ratio of 80 dB. This technique can be employed for the frequency comb and dual-comb operations of terahertz QCLs for high-resolution applications. [ABSTRACT FROM AUTHOR]

As a part of the power system, the stability of the enclosed isolated-phase bus bar (EIPB) plays an important role in the working safety of the power system. Usually, the dynamic-thermal stability of EIPB is analyzed by the theoretical analysis or the finite-element method (FEM). The dynamic stability can be calculated by 2-D model. For the complex structure and huge size of EIPB, large synchronous generator-side EIPB in power system is rarely analyzed. In this paper, a new co-simulation method of EIPB is studied. The subsegments EIPB model based on FEM is established, and the temperature distribution in joint surfaces is transmitted. The method is applied to a certain type of EIPB in power system. The FEM model is simulated. The temperature distribution of EIPB under certain cooling condition is also calculated. Based on the thermal results, the dynamic stability of EIPB is calculated to analyze the electrodynamic force under short-circuit condition. In addition, the feasibility and the validity of the method are proved by the test EIPB. [ABSTRACT FROM AUTHOR]

The article presents research on the acceleration of tumor metastasis through the nuclear factor E2 (NRF2) activation caused by the antioxidant antidiabetic agents. Topics discussed include the association of common type 2 diabetes mellitus drugs with the increased tumor metastasis risk, the correlation of increased NRF2 expression with the metastasis, and eh caution for drug administration among patients.