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Introduction: Lecithin cholesterol acyltransferase (LCAT) plays a crucial role in acyl-esterifying cholesterol in plasma, which is essential for reverse cholesterol transport (RCT). Previous studies indicated that its activity on both α and β lipoproteins interpret its effects on lipoproteins for many controversial investigations of atherosclerosis. Objectives: To better understand the relationship between LCAT, diet-induced dyslipidemia and atherosclerosis, we developed a double knockout (LCAT−/−&LDLR−/−, DKO) hamster model to evaluate the specific role of LCAT independent of LDL clearance effects. Methods: Plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and free cholesterol (FC) levels were measured using biochemical reagent kits. FPLC was performed to analyze the components of lipoproteins. Apolipoprotein content was assessed using western blotting (WB). The hamsters were fed a high cholesterol/high fat diet (HCHFD) to induce atherosclerosis. Oil Red O staining was employed to detect plaque formation. Peritoneal macrophages were studied to investigate the effects of LCAT on cholesterol uptake and efflux. Results: On HCHFD, DKO hamsters exhibited significantly elevated levels of TG and FC, while HDL-C was nearly undetectable without affecting TC levels, as compared to low-density lipoprotein receptor (LDLR)-deficient (LDLR−/−, LKO) hamsters. Lipoprotein profiling revealed a marked increase in plasma chylomicron/very low-density lipoprotein (CM/VLDL) fractions, along with an unexpected reduction in LDL fraction in DKO hamsters. Furthermore, DKO hamsters displayed aggravated atherosclerotic lesions in the aorta, aortic root, and coronary artery relative to LKO hamsters, attributed to a pro-atherogenic lipoprotein profile and impaired cholesterol efflux in macrophages. Conclusions: Our study demonstrates the beneficial role of LCAT in inhibiting atherosclerotic development and highlights the distinctive lipid metabolism characteristics in hamsters with familial hypercholesterolemia.

Abstract The collective modes of the superconducting order parameter fluctuation can provide key insights into the nature of the superconductor. Recently, a family of superconductors has emerged in non-magnetic kagome materials AV3Sb5 (A = K, Rb, Cs), exhibiting fertile emergent phenomenology. However, the collective behaviors of Cooper pairs have not been studied. Here, we report a distinct collective mode in CsV3-x Ta x Sb5 using scanning tunneling microscope/spectroscopy. The spectral line-shape is well-described by one isotropic and one anisotropic superconducting gap, and a bosonic mode due to electron-mode coupling. With increasing x, the two gaps move closer in energy, merge into two isotropic gaps of equal amplitude, and then increase synchronously. The mode energy decreases monotonically to well below $${{2}}{{\Delta }}$$ 2 Δ and survives even after the charge density wave order is suppressed. We propose the interpretation of this collective mode as Leggett mode between different superconducting components or the Bardasis-Schrieffer mode due to a subleading superconducting component.

Abstract Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.

Abstract Background Type 2 diabetes mellitus (T2DM) increases the risk of liver cancer among people living with hepatitis B virus (HBV). Our study aimed to estimate the global burden and trends of liver cancer attributable to comorbid T2DM among people living with HBV from 1990 to 2019. Methods We calculated the population attributable fractions (PAFs) of liver cancer attributable to comorbid T2DM among the burden of HBV-related liver cancer. We applied the PAFs to the burden of HBV-related liver cancer derived from the Global Burden of Disease (GBD) 2019 database to obtain the burden of liver cancer attributable to HBV–T2DM comorbidity. The prevalence, disability-adjusted life year (DALY), and deaths of liver cancer attributable to the comorbidity were assessed at the global, regional, and country levels and then stratified by the sociodemographic index (SDI), sex, and age group. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends. Results In 2019, the global age-standardized prevalence and DALY rates of liver cancer attributable to HBV–T2DM comorbidity were 9.9 (8.4–11.5) and 182.4 (154.9–212.7) per 10,000,000 individuals, respectively. High-income Asia Pacific and East Asia had the highest age-standardized prevalence and DALY rates of liver cancer attributable to HBV–T2DM comorbidity, respectively. From 1990 to 2019, age-standardized prevalence and DALY rates increased in 16 out of 21 GBD regions. High-income North America had the largest annual increases in both age-standardized prevalence rates (EAPC = 6.07; 95% UI, 5.59 to 6.56) and DALY rates (EAPC = 4.77; 95% UI, 4.35 to 5.20), followed by Australasia and Central Asia. Across all SDI regions, the high SDI region exhibited the most rapid increase in age-standardized prevalence and DALY rates from 1990 to 2019. Additionally, men had consistently higher disease burdens than women across all age groups. The patterns of mortality burden and trends are similar to those of DALYs. Conclusions The burden of liver cancer attributable to comorbid T2DM among people living with HBV has exhibited an increasing trend across most regions over the last three decades. Tailored prevention strategies targeting T2DM should be implemented among individuals living with HBV.

Abstract Background Bone marrow mesenchymal stem cells (BMSCs) can undergo inadequate osteogenesis or excessive adipogenesis as they age due to changes in the bone microenvironment, ultimately resulting in decreased bone density and elevated risk of fractures in senile osteoporosis. This study aims to investigate the effects of osteocyte senescence on the bone microenvironment and its influence on BMSCs during aging. Results Primary osteocytes were isolated from 2-month-old and 16-month-old mice to obtain young osteocyte-derived extracellular vesicles (YO-EVs) and senescent osteocyte-derived EVs (SO-EVs), respectively. YO-EVs were found to significantly increase alkaline phosphatase activity, mineralization deposition, and the expression of osteogenesis-related genes in BMSCs, while SO-EVs promoted BMSC adipogenesis. Neither YO-EVs nor SO-EVs exerted an effect on the osteoclastogenesis of primary macrophages/monocytes. Our constructed transgenic mice, designed to trace osteocyte-derived EV distribution, revealed abundant osteocyte-derived EVs embedded in the bone matrix. Moreover, mature osteoclasts were found to release osteocyte-derived EVs from bone slices, playing a pivotal role in regulating the functions of the surrounding culture medium. Following intravenous injection into young and elderly mouse models, YO-EVs demonstrated a significant enhancement of bone mass and biomechanical strength compared to SO-EVs. Immunostaining of bone sections revealed that YO-EV treatment augmented the number of osteoblasts on the bone surface, while SO-EV treatment promoted adipocyte formation in the bone marrow. Proteomics analysis of YO-EVs and SO-EVs showed that tropomyosin-1 (TPM1) was enriched in YO-EVs, which increased the matrix stiffness of BMSCs, consequently promoting osteogenesis. Specifically, the siRNA-mediated depletion of Tpm1 eliminated pro-osteogenic activity of YO-EVs both in vitro and in vivo. Conclusions Our findings suggested that YO-EVs played a crucial role in maintaining the balance between bone resorption and formation, and their pro-osteogenic activity declining with aging. Therefore, YO-EVs and the delivered TPM1 hold potential as therapeutic targets for senile osteoporosis. Graphical abstract

BackgroundLimited epidemiological evidence suggests that exposure to trace elements adversely impacts the development of gastric precancerous lesions (GPL) and gastric cancer (GC). This study aimed to estimate the association of individual urinary exposure to multiple elements with GPL and GC.MethodsA case-control investigation was conducted in Anhui Province from March 2021 to December 2022. A total of 528 subjects (randomly sampled from 1,020 patients with GPL, 200 patients with GC, and 762 normal controls) were included in our study. Urinary levels of iron (Fe), copper (Cu), zinc (Zn), nickel (Ni), strontium (Sr), and Cesium (Cs) were measured using inductively coupled plasma mass spectrometry (ICP-MS). Four different statistical approaches were employed to explore the risk of GPL and GC with mixed exposure, including multivariate logistic regression, weighted quantile regression (WQS), quantile g-computation (Qgcomp), and the Bayesian kernel machine regression (BKMR) model.ResultsThe WQS model indicated that urinary exposure to a mixture of elements is positively correlated with both GPL and GC, with ORs for the mixture exposure of 1.34 (95% CI: 1.34-1.61) for GPL and 1.38 (95% CI: 1.27-1.50) for GC. The Qgcomp and BKMR models also demonstrated a statistically significant positive correlation between the mixture and both GPL and GC.ConclusionConsidering the limitations of case-control studies, future prospective studies are warranted to elucidate the combined effects and mechanisms of trace elements exposure on human health.

Background: The potential for residential greenness to improve cardiovascular health through both physical and psychological mechanisms is well recognized. However, evidence from rapidly urbanizing developing countries and cohort-based causal inference approaches, remains limited. We aim to examine the effect of residential greenness and time to cardiovascular mortality in South China. Methods: We utilized data from a community-based population survey involving 748,209 participants at baseline from 2009 to 2015, followed up until 2020. Residential greenness exposure was assessed by the annual Normalized Difference Vegetation Index (NDVI) in the 500 m radius of each participant’s residence. We used time-varying proportional hazard Cox models coupled with inverse probability weighting to fit marginal structural models and obtain hazard ratios (HRs) for cardiovascular disease (CVD) mortality after adjusting for confounders. Multiple effect modifiers on both additive and multiplicative scales were further explored. Results: A total of 15,139 CVD-related deaths were identified during a median of 7.9 years of follow-up. A protective effect was found between higher greenness exposure and reduced CVD mortality, with a 9.3 % lower rate of total CVD mortality (HR 0.907, 95 % CI 0.859–0.957) based on a 0.1 increase in annual average NDVI. Demographic (age, marital status) and lifestyle factors (smoking, drinking status) were found to modify the association between residential greenness and CVD mortality (all P interaction values

Background: Nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor, is critically involved in the regulation of oxidative stress and inflammation. However, the role of endothelial Nrf2 in atherogenesis has yet to be defined. In addition, how endothelial Nrf2 is activated and whether Nrf2 can be targeted for the prevention and treatment of atherosclerosis is not explored. Methods: RNA-sequencing and single-cell RNA sequencing analysis of mouse atherosclerotic aortas were used to identify the differentially expressed genes. In vivo endothelial cell (EC)-specific activation of Nrf2 was achieved by injecting adeno-associated viruses into ApoE−/− mice, while EC-specific knockdown of Nrf2 was generated in Cdh5CreCas9floxed-stopApoE−/− mice. Results: Endothelial inflammation appeared as early as on day 3 after feeding of a high cholesterol diet (HCD) in ApoE−/− mice, as reflected by mRNA levels, immunostaining and global mRNA profiling, while the immunosignal of the end-product of lipid peroxidation (LPO), 4-hydroxynonenal (4-HNE), started to increase on day 10. TNF-α, 4-HNE, and erastin (LPO inducer), activated Nrf2 signaling in human ECs by increasing the mRNA and protein expression of Nrf2 target genes. Knockdown of endothelial Nrf2 resulted in augmented endothelial inflammation and LPO, and accelerated atherosclerosis in Cdh5CreCas9floxed-stopApoE−/− mice. By contrast, both EC-specific and pharmacological activation of Nrf2 inhibited endothelial inflammation, LPO, and atherogenesis. Conclusions: Upon HCD feeding in ApoE−/− mice, endothelial inflammation is an earliest event, followed by the appearance of LPO. EC-specific activation of Nrf2 inhibits atherosclerosis while EC-specific knockdown of Nrf2 results in the opposite effect. Pharmacological activators of endothelial Nrf2 may represent a novel therapeutic strategy for the treatment of atherosclerosis.

Introduction Postoperative radiotherapy in patients with breast cancer with one to three lymph node metastases, particularly within the pT1–2N1M0 cohort with a low clinical risk of local–regional recurrence (LRR), has incited a discourse surrounding personalised treatment strategies. Multigene testing for Recurrence Index (RecurIndex) model capably differentiates patients based on their level of LRR risk. This research aims to validate whether a more aggressive treatment approach can enhance clinical outcomes in N1 patients who possess a clinically low risk of LRR, yet a high RecurIndex-determined risk of LRR. Specifically, this entails postoperative whole breast irradiation combined with regional lymph node irradiation (RNI) following breast-conserving surgery or chest wall irradiation with RNI after mastectomy.Methods and analysis The RIGAIN (RecurIndex-Guided postoperative radiotherapy with or without Avoidance of Irradiation of regional Nodes in 1–3 node-positive breast cancer) Study is a multicentre, prospective, randomised, open-label, phase III clinical trial that is being conducted in China. In this study, patients with low clinical LRR risk but high RecurIndex-LRR risk are randomly assigned in a 1:1 ratio to the experimental group or the control group. In the experimental group, RNI is performed and the control group omits RNI. Efficacy and safety analyses will be conducted, enrolling a total of 540 patients (270 per group). The primary endpoint is invasive disease-free survival, and secondary endpoints include any first recurrence, LRR-free survival, distant metastasis-free survival, recurrence-free survival, overall survival, disease-free survival, breast cancer-specific mortality and assessment of patient quality of life. The study began in April 2023 and with a follow-up period of 60 months after the last participant completes radiation therapy.Ethics and dissemination The study was approved by the Ethics Committee of Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University (SYSKY-2022-097-02, V.3.1). It adheres to the Helsinki Declaration and Good Clinical Practice. Research findings will be submitted for publication in peer-reviewed journals.Trial registration number NCT04069884.

Chimeric antigen receptor T-cell (CAR-T) therapy, which has demonstrated notable efficacy against B-cell malignancies and is approved by the US Food and Drug Administration for clinical use in this context, represents a significant milestone in cancer immunotherapy. However, the efficacy of CAR-T therapy for the treatment of acute myeloid leukemia (AML) is poor. The challenges associated with the application of CAR-T therapy for the clinical treatment of AML include, but are not limited to, nonspecific distribution of AML therapeutic targets, difficulties in the production of CAR-T cells, AML blast cell heterogeneity, the immunosuppressive microenvironment in AML, and treatment-related adverse events. In this review, we summarize the recent findings regarding various therapeutic targets for AML (CD33, CD123, CLL1, CD7, etc.) and the results of the latest clinical studies on these targets. Thereafter, we also discuss the challenges related to CAR-T therapy for AML and some promising strategies for overcoming these challenges, including novel approaches such as gene editing and advances in CAR design.

The mechanical stress environment in the temporomandibular joint (TMJ) is constantly changing due to daily mandibular movements. Therefore, TMJ tissues, such as condylar cartilage, the synovial membrane and discs, are influenced by different magnitudes of mechanical stimulation. Moderate mechanical stimulation is beneficial for maintaining homeostasis, whereas abnormal mechanical stimulation leads to degeneration and ultimately contributes to the development of temporomandibular joint osteoarthritis (TMJOA), which involves changes in critical signaling molecules. Under abnormal mechanical stimulation, compensatory molecules may prevent degenerative changes while decompensatory molecules aggravate. In this review, we summarize the critical signaling molecules that are stimulated by moderate or abnormal mechanical loading in TMJ tissues, mainly in condylar cartilage. Furthermore, we classify abnormal mechanical stimulation-induced molecules into compensatory or decompensatory molecules. Our aim is to understand the pathophysiological mechanism of TMJ dysfunction more deeply in the ever-changing mechanical environment, and then provide new ideas for discovering effective diagnostic and therapeutic targets in TMJOA.

Abstract Purpose The purpose of this study was to investigate immunological variations between a group that received the hepatitis B vaccine and a non-vaccine group. We focused on a cohort that achieved HBsAg seroclearance after Peg-IFNα treatment of CHB. Methods We enrolled twenty-eight individuals who achieved HBsAg seroclearance after Peg-IFNα treatment. They were divided into two groups: a vaccine group (n = 14) and a non-vaccine group (n = 14). We assessed lymphocyte subpopulations, B cell- and T cell-surface costimulatory/inhibitory factors, cytokines and immunoglobulin levels were detected at different time points to explore immune-function differences between both groups. Results The seroconversion rate in the vaccine group at 24 weeks post-vaccination was 100%, which was significantly higher (p = 0.006) than that of the non-vaccine group (50%). Additionally, more individuals in the vaccine group exhibited anti-HBs levels exceeding 100 IUs/L and 300 IUs/L compared to the non-vaccine group (p 0.05). Total IgG increased significantly in the vaccine group, and IL-2, IL-5, and IL-6 concentrations increased significantly at week 24 (p 0.05). Anti-HBs titers positively correlated with Th1/Th2 cells at 24 weeks (r = 0.448 and 0.458, respectively, p = 0.022 and 0.019, respectively), and negatively with CD24+CD38highBreg cells (r = -0.402, p = 0.042). Conclusions After achieving HBsAg seroclearance through Peg-IFNα treatment for CHB, administering the hepatitis B vaccine significantly increased anti-HBs-seroconversion rates and antibody levels. We also observed significant immunological differences between the vaccine and non-vaccine groups. Specifically, the vaccine group exhibited significant increases in B cells, plasma cells, and Tfh cells, while Breg levels was significantly lower. These immunological changes are likely conducive to the production of anti-HBs antibodies. However, in the non-vaccine group, the observed changes were not significantlly significant.

Abstract The oncogenic role of circRNA in cancers including esophageal cancer (EC) has been well studied. However, whether and how circRNAs are involved in cancer cell metabolic processes remains largely unknown. Here, we reported that circRNA, circHIPK3, is highly expressed in ESCC cell lines and tissues. Knockdown of circHIPK3 significantly restrained cell proliferation, colony formation, migration, and invasion in vitro and inhibited tumor growth in vivo. Mechanistically, circHIPK3 was found to act as a ceRNA by sponging miR-637 to regulate FASN expression and fatty acid metabolism in ESCC cells. Anti-sense oligonucleotide (ASO) targeting circHIPK3 substantially inhibited ESCC both in vitro and in vivo. Therefore, these results uncover a modulatory axis constituting of circHIPK3/miR-637/FASN may be a potential biomarker and therapeutic target for ESCC in the clinic.

Hyperbaric oxygen therapy characterized by fewer side effects and simple operation has been explored as a potential therapy for depression. This article provides a review of researches relevant to current clinical application and mechanism of hyperbaric oxygen therapy for depression， aiming to provide valuable references for the formulation of new strategies for the treatment of depression. Hyperbaric oxygen therapy has been demonstrated to be useful as an adjunctive therapy for depression， which can effectively alleviate depression by regulating the homeostasis of hypothalamus-pituitary-adrenal axis， inhibiting inflammation and enhancing synaptic plasticity. And hyperbaric oxygen therapy as adjuvant to antidepressants for depression can contribute to increasing the treatment effectiveness to some extent.

Abstract Anisotropic planar polaritons - hybrid electromagnetic modes mediated by phonons, plasmons, or excitons - in biaxial two-dimensional (2D) van der Waals crystals have attracted significant attention due to their fundamental physics and potential nanophotonic applications. In this Perspective, we review the properties of planar hyperbolic polaritons and the variety of methods that can be used to experimentally tune them. We argue that such natural, planar hyperbolic media should be fairly common in biaxial and uniaxial 2D and 1D van der Waals crystals, and identify the untapped opportunities they could enable for functional (i.e. ferromagnetic, ferroelectric, and piezoelectric) polaritons. Lastly, we provide our perspectives on the technological applications of such planar hyperbolic polaritons.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS–USP25 protein–protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS–USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APCmin/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS–USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Summary: Background: A variety of symptoms, particularly cognitive, psychiatric and neurological symptoms, may persist for a long time among individuals recovering from COVID-19. However, the underlying mechanism of these brain abnormalities remains unclear. This study aimed to investigate the long-term neuroimaging effects of COVID-19 infection on brain functional activities using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Fifty-two survivors 27 months after infection (mild-moderate group: 25 participants, severe-critical: 27 participants), from our previous community participants, along with 35 healthy controls, were recruited to undergo fMRI scans and comprehensive cognitive function measurements. Participants were evaluated by subjective assessment of Cognitive Failures Questionnaire-14 (CFQ-14) and Fatigue Scale-14 (FS-14), and objective assessment of Montreal Cognitive Assessment (MoCA), N-back, and Simple Reaction Time (SRT). Each had rs-fMRI at 3T. Measures such as the amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) were calculated. Findings: Compared with healthy controls, survivors of mild-moderate acute symptoms group and severe-critical group had a significantly higher score of cognitive complains involving cognitive failure and mental fatigue. However, there was no difference of cognitive complaints between two groups of COVID-19 survivors. The performance of three groups was similar on the score of MoCA, N-back and SRT. The rs-fMRI results showed that COVID-19 survivors exhibited significantly increased ALFF values in the left putamen (PUT.L), right inferior temporal gyrus (ITG.R) and right pallidum (PAL.R), while decreased ALFF values were observed in the right superior parietal gyrus (SPG.R) and left superior temporal gyrus (STG.L). Additionally, decreased ReHo values in the right precentral gyrus (PreCG.R), left postcentral gyrus (PoCG.L), left calcarine fissure and surrounding cortex (CAL.L) and left superior temporal gyrus (STG.L). Furthermore, significant negative correlations between the ReHo values in the STG.L, and CFQ-14 and mental fatigue were found. Interpretation: This long-term study suggests that individuals recovering from COVID-19 continue to experience cognitive complaints, psychiatric and neurological symptoms, and brain functional alteration. The rs-fMRI results indicated that the changes in brain function in regions such as the putamen, temporal lobe, and superior parietal gyrus may contribute to cognitive complaints in individuals with long COVID even after 2-year infection. Funding: The National Programs for Brain Science and Brain-like Intelligence Technology of China, the National Natural Science Foundation of China, Natural Science Foundation of Beijing Municipality of China, and the National Key Research and Development Program of China.

Background: and purpose: Radiotherapy (RT) is an effective treatment for most malignant chest tumors. However, radiation-induced myocardial fibrosis (RIMF) is a serious side effect of RT. Currently, due to the mechanism of RIMF has not been fully elucidated, there is a lack of effective therapeutic approach. In this study, we aimed to investigate the role and possible mechanisms of bone marrow mesenchymal stem cells (BMSCs) in the therapy of RIMF. Materials and methods: Twenty-four New Zealand white rabbits were allotted into four groups (n = 6). Rabbits in the Control group received neither irradiation nor treatment. A single dose of 20 Gy heart X-irradiation was applied to the RT group, RT + PBS group and RT + BMSCs group. Rabbits in the RT + PBS group and RT + BMSCs group were injected with 200 μL PBS or 2 × 106 cells via pericardium puncture 24 h following irradiation, respectively. Echocardiography was used to test the cardiac function; Then the heart samples were collected, and processed for histopathological, Western blot and immunohistochemistry investigations. Results: It was observed that BMSCs have therapeutic effect on RIMF. Compared with the Control group, inflammatory mediators, oxidative stress and apoptosis were significantly increased, meanwhile, cardiac function was remarkably decreased in the RT group and RT + PBS group. However, in the BMSCs group, BMSCs significantly improved cardiac function, decreased inflammatory mediators, oxidative stress and apoptosis. Furthermore, BMSCs remarkably reduced the expression level of TGF-β1 and the phosphorylated-Smad2/3. Conclusions: In conclusion, our research indicates BMSCs have the potential to alleviate RIMF through TGF-β1/Smad2/3 and would be a new therapeutic approach for patients with myocardial fibrosis.

Abstract Phase retrieval in holographic data storage by expanded spectrum combined with dynamic sampling method is proposed, which serves to both reduce media consumption and to shorten the iterative number of phase code retrieval. Generally, high-fidelity phase retrieval requires twice Nyquist frequency in phase-modulated holographic data storage. To increase storage density, we only recorded and captured the signal with Nyquist size and used the frequency expanded method to realize high-fidelity phase retrieval. In the decoding process, the iterative Fourier transform algorithm is used to retrieve the phase information of the reconstructed beam. The expanded spectrum is dynamically sampled, which can provide a faster convergence path for the phase retrieval. We aimed to demonstrate the possibility of integrating various methods on the Fourier domain and providing a potential way to improve the performance of holographic data storage systems. The simulation and experimental results proved the combination of processing methods in frequency spectrum was benefit.

To further investigate the impact of layered deposition process on the magnetic properties of sintered Nd–Fe–B magnets, the multicomponent Tb–Cu films with different deposition sequences were designed through magnetron sputtering system. We first examined the effects of heat treatment, pure Cu and pure Tb diffusion on the magnetic properties of original magnets. For multicomponent Tb–Cu diffused magnets, we found that the deposition amount of Cu was an important factor in studying the diffusion mechanism of Tb–Cu films during grain boundary diffusion process. The deposition of Cu in moderation could significantly increase the diffusion depth of Tb due to the reduction in the enrichment of Tb near the surface. The deposition of excessive Cu reduced the diffusion efficiency of Tb, even lower than that of Tb in pure Tb diffused magnet. The results showed that the sequence of Tb deposition followed by Cu deposition in moderation was the optimal deposition order to achieve higher synthetical magnetic properties. Moreover, we investigated the negative impact of the Tb-rich zone on magnetic properties and proposed structural models for different diffused magnets.

In this study, the current noise situation in eight hospitals in central and northern Taiwan was investigated and analyzed. Recording equipment was utilized to measure environmental noise levels at the busiest points in the hospital lobby, specifically the pricing and medicine waiting areas. Furthermore, the acoustic data of the recorded audio samples were analyzed to determine the psychoacoustic parameter, namely, loudness. Subsequently, correlation analysis was performed between the analyzed data spectrum and the subjective psychological noise value. Ultimately, it was found that the mid-frequency band (MF) had a greater impact on the subjects compared to the other two frequency bands. When comparing the correlation coefficient analysis with the prior factor analysis, the primary sources of intrusive noise affecting the subjects were identified. The mid-frequency band is predominantly attributed to footsteps and conversations, and the high-frequency band is predominantly attributed to broadcast sound.

In the past, comprehensive information was imperative for image processing, prompting a preference for high-depth cameras. However, in our research, we discovered that the abundance of image details may impede phase retrieval. Consequently, this paper presents an iterative phase retrieval method based on a low bit depth. Through simulations and experiments, this approach has proven effective in evidently enhancing phase retrieval outcomes. Furthermore, the concept of low bit depth holds promise for broader application across diverse domains within the field of image retrieval.

Abstract In recent decades, ecological niche models (ENMs) have been widely used to predict suitable habitats for species. However, for invasive organisms, the prediction accuracy is unclear. In this study, we employed the most widely used maximum entropy (MaxEnt) model and ensemble model (EM) Biomod2 and verified the practical effectiveness of the ENM in predicting the distribution areas of invasive insects based on the true occurrence of Hyphantria cunea in China. The results showed that when only limited data of invasive areas were used, the two ENMs could not effectively predict the distribution of suitable habitats of H. cunea, although the use of global data can greatly improve the prediction accuracy of ENMs. When analyzing the same data, Biomod2's prediction accuracy was significantly better than that of MaxEnt. For long‐term predictions, the area of suitable habitat predicted by the ENMs was much greater than the occurrence area; for short‐term predictions, the accuracy of the predicted area was significantly improved. Under the current conditions, the area of suitable habitat for H. cunea in China is 118 × 104 km2, of which 59.32% is moderately or highly suitable habitat. Future climate change could significantly increase the suitable habitat area of H. cunea in China, and the predicted area of suitable habitats in all climate scenarios exceeded 355 × 104 km2, accounting for 36.98% of the total land area in China. This study demonstrates the use of ENMs to study invasive insects and provides a reference for the management of H. cunea in China.

This study, which considers the exchange that occurs between civilisations, attempts to re-examine the question pertaining to the authenticity of sutra. The Guanjing [Guan Wulingshou jing 觀無量壽經 Skt. Amitāyur Dhyāna Sūtra; Contemplation Sūtra], which is an influential Buddhist text, immensely facilitated the first transmission of Zen Buddhism that occurred during the Middle Ages, and it promoted the spread of the Pure Land thought. Because of the modern academic research on the Chinese Buddhist Apocrypha, the discussion pertaining to the authenticity of the Guanjing has become prominent, and for more than half a century, issues pertaining to the place in which it was compiled, the time of its establishment and the absence of the Sanskrit and Tibetan texts have received research attention. Buddhist texts have spread from India to China. If a general literature and linguistics perspective is adopted, the availability of a sutra in the original Indian language becomes a criterion for determining its reliability and authenticity. In addition, the translator, the place in which the translation occurred, the time of translation and the relationship with similar scriptures are all significant factors that can determine whether a sutra is an allegedly forged manuscript. Contribution: This article contributes to the understanding of the authenticity and counterfeit nature of Guanjing through a civilisational exchange perspective. This study differs from previous thinking only in terms of Sinicized sects, and the article analyses the possible Indian and Central Asian sources of the text, pointing out the forms in which the Guanjing and Ajātaśatru are reflected.

The rapid increase in e-commerce and the emergence of combined passenger/freight systems in urban areas have raised the question of how best to integrate public transport services into door-to-door deliveries. This paper develops a variant of the pickup and delivery problem, called the two-echelon pickup and delivery problem using public transport (2E-PDP-PT). In the 2E-PDP-PT, the transportation network is split into two echelons. Different vehicles are utilized across the first and second echelons to ensure distribution efficiency. Parcels are delivered by public transport with free capacity or via trucks between satellites in the first echelon, and logistics vehicles are operated in the second echelon. The satellites are located at the echelon borders to transfer commodities between echelons. The 2E-PDP-PT aims to minimize total delivery costs and improve public transport capacity utilization. We formulate a new mathematical model based on a space-time network and adopt an adaptive large neighborhood search (ALNS) algorithm for the 2E-PDP-PT. The effectiveness of the ALNS algorithm is validated using newly generated small-scale instances. Furthermore, we investigate large-scale instances based on the Beijing Yizhuang transportation network. The computations show that an average total delivery cost savings of 4.5% is feasible. In addition, we analyze the impact of demand distributions and compare the ALNS algorithm and the LNS algorithm. Finally, we conclude that dynamically integrating public transport into freight transport services can benefit both logistics companies and public transport operators.

Osteoarthritis (OA) is a major cause of disability, characterized by chronic pain, irreversible destruction, and loss of function of the articular cartilage. The integrity and arrangement of the composition and structure of the extracellular matrix (ECM) are essential for maintaining the elasticity, integrity, and mechanical support function of the cartilage tissue. Osteoarthritis causes substantial changes in the ECM, driving the progression of the disease. Recent studies have shown that the ECM plays a critical role in the development of cartilage tissue as well as the occurrence and development of osteoarthritis by directly or indirectly regulating chondrocyte proliferation, apoptosis, differentiation, and gene expression. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs derived from large transcripts. Mutations and disorders of lncRNAs are closely related to the development of osteoarthritis. Abnormal expression of lncRNAs in osteoarthritic cartilage regulates the synthesis and decomposition of the cartilaginous ECM. Therefore, the use of lncRNAs as nucleic acid drugs that regulate their targets may reduce ECM degradation, thereby delaying the pathological progression of osteoarthritis. In this review, the regulatory effects of lncRNAs on ECM in different cell behaviors related to OA are summarized. The roles of lncRNAs in the proliferation, apoptosis, differentiation, and ECM-related gene activity of chondrocytes, as well as the application of lncRNAs as potential gene therapy drugs for the repair and regeneration of osteoarthritic tissue, are also reviewed. A better understanding of the roles of lncRNAs in guiding chondrocyte behavior and ECM metabolism is critical for their future applications in osteoarthritis therapy and regenerative medicine.

Abstract The coexistence of electric dipoles and itinerant electrons in a solid was postulated decades ago, before being experimentally established in several ‘polar metals’ during the last decade. Here, we report a concentration-driven polar-to-nonpolar phase transition in electron-doped BaTiO3. Comparing our case with other polar metals, we find a particular threshold concentration (n *) linked to the dipole density (n d). The universal ratio $$\frac{{n}_{{{{\rm{d}}}}}}{{n}^{* }}\approx 8.0(6)$$ n d n * ≈ 8.0 ( 6 ) suggests a common mechanism across different polar systems, possibly explained by a dipolar Ruderman-Kittel-Kasuya-Yosida theory. Moreover, in BaTiO3, we observe enhanced thermopower and upturn on resistivity at low temperatures near n *, resembling the Kondo effect. We argue that local electric dipoles act as two-level-systems, whose fluctuations couple with surrounding electron clouds, giving rise to a potential dipolar-counterpart of the Kondo effect. Our findings unveil a mostly uncharted territory for exploring emerging physics associated with electron-dipole correlations, encouraging further theoretical work on dipolar-RKKY and Kondo interactions.

Abstract Background Porcine epidemic diarrhea virus (PEDV) and porcine delta-coronavirus (PDCoV) are economically important pathogens that cause diarrhea in sows and acute death of newborn piglets. Moreover, the emerging PDCoV was reported to infect children. The current situation is that vaccine prevention has not met expectations, and emergency containment strategies following outbreaks cannot prevent the damages and losses already incurred. Therefore, a more sensitive detection method, that is both convenient and enables accurate and effective sequencing, that will provide early warning of PEDV and PDCoV is necessary. This will enable active, effective, and comprehensive prevention and control, which will possibly reduce disease occurrences. Results Duplex nested RT-PCR (dnRT-PCR) is an ideal method to achieve early warning and monitoring of PEDV and PDCoV diseases, and to additionally investigate any molecular epidemiological characteristics. In this study, two pairs of primers were designed for each virus based upon the highly conserved N protein sequences of both PEDV and PDCoV strains retrieved from the NCBI Genbank. After optimization of the reaction conditions, the dnRT-PCR assay amplified a 749-bp fragment specific to PEDV and a 344-bp fragment specific to PDCoV. Meanwhile, the specificity and sensitivity of the primers and clinical samples were tested to verify and establish this dnRT-PCR method. The limit of detection (LoD)for both PEDV and PDCoV was 10 copies/µL. The results showed that among 251 samples, 1 sample contained PEDV infection, 19 samples contained a PDCoV infection, and 8 samples were infected with both viruses, following the use of dnRT-PCR. Subsequently, the positive samples were sent for sequencing, and the sequencing results confirmed that they were all positive for the viruses detected using dnRT-PCR, and conventional RT-PCR detection was conducted again after the onset of disease. As these results were consistent with previous results, a detection method for PEDV and PDCoV using dnRT-PCR was successfully established. In conclusion, the dnRT-PCR method established in this study was able to detect both PEDV and PDCoV, concomitantly. Conclusions The duplex nested RT-PCR method represents a convenient, reliable, specific, sensitive and anti-interference technique for detecting PEDV and PDCoV, and can additionally be used to simultaneously determine the molecular epidemiological background.

Abstract Vascular calcification often occurs in patients with chronic renal failure (CRF), which significantly increases the incidence of cardiovascular events in CRF patients. Our previous studies identified the crosstalk between the endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and the paracrine effect of VSMCs, which regulate the calcification of VSMCs. Herein, we aim to investigate the effects of exosomes secreted by high phosphorus (HPi) -induced adventitial fibroblasts (AFs) on the calcification of VSMCs and the underlying mechanism, which will further elucidate the important role of AFs in high phosphorus vascular wall microenvironment. The conditioned medium of HPi-induced AFs promotes the calcification of VSMCs, which is partially abrogated by GW4869, a blocker of exosomes biogenesis or release. Exosomes secreted by high phosphorus-induced AFs (AFsHPi-Exos) show similar effects on VSMCs. miR-21-5p is enriched in AFsHPi-Exos, and miR-21-5p enhances osteoblast-like differentiation of VSMCs by downregulating cysteine-rich motor neuron 1 (Crim1) expression. AFsHPi-Exos and exosomes secreted by AFs with overexpression of miR-21-5p (AFsmiR21M-Exos) significantly accelerate vascular calcification in CRF mice. In general, AFsHPi-Exos promote the calcification of VSMCs and vascular calcification by delivering miR-21-5p to VSMCs and subsequently inhibiting the expression of Crim1. Combined with our previous studies, the present experiment supports the theory of vascular wall microenvironment. Graphical Abstract

The bacterial trialkyl-substituted aromatic polyketides are structurally featured with the unusual aromatic core in the middle of polyketide chain such as TM-123 (1), veramycin A (2), NFAT-133 (3) and benwamycin I (4), which were discovered from Streptomyces species and demonstrated with antidiabetic and immunosuppressant activities. Though the biosynthetic pathway of 1−3 was reported as a type I polyketide synthase (PKS), the PKS assembly line was interpreted inconsistently, and it remains a mystery how the compound 3 was generated. Herein, the PKS assembly logic of 1−4 was revised by site-mutagenetic analysis of the PKS dehydratase domains. Based on gene deletion and complementation, the putative P450 monooxygenase nftE1 and metallo-beta-lactamase (MBL) fold hydrolase nftF1 were verified as essential genes for the biosynthesis of 1−4. The absence of nftE1 led to abolishment of 1−4 and accumulation of new products (5−8). Structural elucidation reveals 5−8 as the non-aromatic analogs of 1, suggesting the NftE1-catalyzed aromatic core formation. Deletion of nftF1 resulted in disappearance of 3 and 4 with the compounds 1 and 2 unaffected. As a rare MBL-fold hydrolase from type I PKSs, NftF1 potentially generates the compound 3 through two strategies: catalyze premature chain-offloading as a trans-acting thioesterase or hydrolyze the lactone-bond of compound 1 as an esterase.

Abstract Kagome-lattice materials possess attractive properties for quantum computing applications, but their synthesis remains challenging. Herein, based on the compelling identification of the two cleavable surfaces of Co3Sn2S2, we show surface kagome electronic states (SKESs) on a Sn-terminated triangular Co3Sn2S2 surface. Such SKESs are imprinted by vertical p-d electronic hybridization between the surface Sn (subsurface S) atoms and the buried Co kagome-lattice network in the Co3Sn layer under the surface. Owing to the subsequent lateral hybridization of the Sn and S atoms in a corner-sharing manner, the kagome symmetry and topological electronic properties of the Co3Sn layer is proximate to the Sn surface. The SKESs and both hybridizations were verified via qPlus non-contact atomic force microscopy (nc-AFM) and density functional theory calculations. The construction of SKESs with tunable properties can be achieved by the atomic substitution of surface Sn (subsurface S) with other group III-V elements (Se or Te), which was demonstrated theoretically. This work exhibits the powerful capacity of nc-AFM in characterizing localized topological states and reveals the strategy for synthesis of large-area transition-metal-based kagome-lattice materials using conventional surface deposition techniques.

Abstract Introduction Ischemic stroke accounts for 70–80% of all stroke cases, leading to over two million people dying every year. Poor diagnosis and late detection are the major causes of the high death and disability rate. Methods In the present study, we used the middle cerebral artery occlusion (MCAO) rat model and applied comparative transcriptomic analysis, followed by a systematic advanced bioinformatic analysis, including gene ontology enrichment analysis and Ingenuity Pathway Analysis (IPA). We aimed to identify novel biomarkers for the early detection of ischemic stroke. In addition, we aimed to delineate the molecular mechanisms underlying the development of ischemic stroke, in which we hoped to identify novel therapeutic targets for treating ischemic stroke. Results In the comparative transcriptomic analysis, we identified 2657 differentially expressed genes (DEGs) in the brain tissue of the MCAO model. The gene enrichment analysis highlighted the importance of these DEGs in oxygen regulation, neural functions, and inflammatory and immune responses. We identified the elevation of angiopoietin-2 and leptin receptor as potential novel biomarkers for early detection of ischemic stroke. Furthermore, the result of IPA suggested targeting the inflammasome pathway, integrin-linked kinase signaling pathway, and Th1 signaling pathway for treating ischemic stroke. Conclusion The results of the present study provide novel insight into the biomarkers and therapeutic targets as potential treatments of ischemic stroke.

Abstract Medial arterial calcification (MAC), a systemic vascular disease different from atherosclerosis, is associated with an increased incidence of cardiovascular events. Several studies have demonstrated that ambient temperature is one of the most important factors affecting cardiovascular events. However, there has been limited research on the effect of different ambient temperatures on MAC. In the present study, we showed that cold temperature exposure (CT) in mice slowed down the formation of vitamin D (VD)-induced vascular calcification compared with room temperature exposure (RT). To investigate the mechanism involved, we isolated plasma-derived exosomes from mice subjected to CT or RT for 30 days (CT-Exo or RT-Exo, respectively). Compared with RT-Exo, CT-Exo remarkably alleviated the calcification/senescence formation of vascular smooth muscle cells (VSMCs) and promoted autophagy by activating the phosphorylation of AMP-activated protein kinase (p-AMPK) and inhibiting phosphorylation of mammalian target of rapamycin (p-mTOR). At the same time, CT-Exo promoted autophagy in β-glycerophosphate (β-GP)-induced VSMCs. The number of autophagosomes and the expression of autophagy-related proteins ATG5 and LC3B increased, while the expression of p62 decreased. Based on a microRNA chip microarray assay and real-time polymerase chain reaction, miR-320a-3p was highly enriched in CT-Exo as well as thoracic aortic vessels in CT mice. miR-320a-3p downregulation in CT-Exo using AntagomiR-320a-3p inhibited autophagy and blunted its anti-calcification protective effect on VSMCs. Moreover, we identified that programmed cell death 4 (PDCD4) is a target of miR-320a-3p, and silencing PDCD4 increased autophagy and decreased calcification in VSMCs. Treatment with CT-Exo alleviated the formation of MAC in VD-treated mice, while these effects were partially reversed by GW4869. Furthermore, the anti-arterial calcification protective effects of CT-Exo were largely abolished by AntagomiR-320a-3p in VD-induced mice. In summary, we have highlighted that prolonged cold may be a good way to reduce the incidence of MAC. Specifically, miR-320a-3p from CT-Exo could protect against the initiation and progression of MAC via the AMPK/mTOR autophagy pathway. Graphic Abstract

Abstract Background With the rise of reported mental disorders and behavioral issues after the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, psychiatrists and mental health care are urgently needed more than ever before. The psychiatric career carries a high emotional burden and stressful demands, which bring issues on psychiatrists’ mental health and well-being into question. To investigate the prevalence and risk factors of depression, anxiety, and work burnout among psychiatrists in Beijing during the COVID-19 pandemic. Methods This cross-sectional survey was conducted from January 6 to January 30, 2022, two years after COVID-19 was declared a global pandemic. Recruitment was performed using a convenience sample approach by sending online questionnaires to psychiatrists in Beijing. The symptoms of depression, anxiety, and burnout were evaluated using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Maslach Burnout Inventory-General Survey (MBI-GS). The perceived stress and social support were measured by the Chinese Perceived Stress Scale (CPSS) and Social Support Rating Scale (SSRS), respectively. Results The data of 564 psychiatrists (median [interquartile range] age, 37 [30–43] years old) of all 1532 in Beijing were included in the statistical analysis. The prevalence of symptoms of depression, anxiety and burnout were 33.2% (95% CI, 29.3-37.1%, PHQ-9 ≥ 5), 25.4% (95% CI, 21.8-29.0%, GAD-7 ≥ 5) and 40.6% (95% CI, 36.5-44.7%, MBI-GS ≥ 3 in each of the three subdimensions), respectively. The psychiatrist with a higher score on perceived stress was more likely to suffer from depressive symptoms (adjusted odds ratios [ORs]: 4.431 [95%CI, 2.907–6.752]); the anxiety symptoms (adjusted ORs: 8.280 [95%CI, 5.255–13.049]), and the burnout conditions (adjusted ORs: 9.102 [95%CI, 5.795–14.298]). Receiving high social support was an independent protective factor against symptoms of depression (adjusted ORs: 0.176 [95%CI, [0.080–0.386]), anxiety (adjusted ORs: 0.265 [95%CI, 0.111–0.630]) and burnout (adjusted ORs: 0.319 [95%CI, 0.148–0.686]). Conclusions Our data suggest a considerable proportion of psychiatrists also suffer from depression, anxiety, and burnout. Perceived stress and social support influence depression, anxiety, and burnout. For public health, we must work together to reduce the pressure and increase social support to mitigate mental health risks in psychiatrists.

Silkworm (Bombyx mori) pupae are popular edible insects with high nutritional and therapeutic value. Currently, there is growing interest in the comprehensive application of silkworm pupae. In this study, peptides that exhibited anti-photoaging activity were obtained from silkworm pupae protein, aiming to investigate the protective effects and potential mechanisms of silkworm pupae peptides (SPPs) on skin photoaging. The results showed that SPPs were composed of 900 short peptides and could effectively alleviate skin photoaging progression. They significantly eliminated excessive production of ROS and MDA; meanwhile, they also renovated the antioxidant enzyme activities. The biomarkers related to collagen synthesis and degradation, including hydroxyproline, interstitial collagenase, and gelatinase, demonstrated that SPPs could suppress collagen degradation. Histopathological results showed that SPPs could reduce the inflammatory infiltrate and the thickness of the dermis and epidermis, as well as increase the collagen bundles and muscle fibers. The histopathological and biochemical results confirmed that SPPs could alleviate photoaging by inhibiting abnormal skin changes, reducing oxidative stress, and immune suppression. Overall, these data prove the protective effects of SPPs against the photoaging process, suggesting their potential as an active ingredient in skin photoaging prevention and therapy.

Four new cyclic pentapeptides, avellanins D–G (1–4), together with four known compounds (5–8), were isolated from a mangrove-derived Aspergillus fumigatus GXIMD 03099 fungus from Acanthus ilicifolius L. Their structures were elucidated by analysis of HRESIMS, NMR, and ESI-MS/MS data. Their absolute configurations were determined by X-ray diffraction analysis and Marfey’s method. Compounds 1–8 were screened for insecticidal and antibacterial activities. Compound 2 showed insecticidal activity against newly hatched larvae of Culex quinquefasciatus with an LC50 value of 86.6 µM; compound 4 had weak activity against Vibrio harveyi with an MIC value of 5.85 µM.

In this paper, we delve into the dynamics of two and three coupled SRRs models, exploring their nonlinear properties such as stability, periodicity, or chaos. Additionally, we examine the energy function Hamilton within the context of these models. Numerical examples are provided to illustrate the obtained results and demonstrate the applicability of our findings.

Phenanthrenequinone-doped poly(methyl methacrylate) (PQ/PMMA) photopolymers are potential holographic storage media owing to their high-density storage capacities, low costs, high stability, and negligible shrinkage in volume holographic permanent memory. However, because of the limitations of the substrate, conventional Plexiglas materials do not exhibit a good performance in terms of photosensitivity and molding. In this study, the crosslinked structure of PMMA was modified by introducing a dendrimer monomer, pentaerythritol tetraacrylate (PETA), which increases the photosensitivity of the material 2 times (from ~0.58 cm/J to ~1.18 cm/J), and the diffraction efficiency is increased 1.6 times (from ~50% to ~80%). In addition, the modified material has a superior ability to mold compared to conventional materials. Moreover, the holographic performance enhancement was evaluated in conjunction with a quantum chemical analysis. The doping of PETA resulted in an overall decrease in the energy required for the reaction system of the material, and the activation energy decreased by ~0.5 KJ/mol in the photoreaction stage.

Stem cells (SCs) undergo asymmetric division, producing transit-amplifying cells (TACs) with increased proliferative potential that move into tissues and ultimately differentiate into a specialized cell type. Thus, TACs represent an intermediary state between stem cells and differentiated cells. In the cornea, a population of stem cells resides in the limbal region, named the limbal epithelial stem cells (LESCs). As LESCs proliferate, they generate TACs that move centripetally into the cornea and differentiate into corneal epithelial cells. Upon limbal injury, research suggests a population of progenitor-like cells that exists within the cornea can move centrifugally into the limbus, where they dedifferentiate into LESCs. Herein, we summarize recent advances made in understanding the mechanism that governs the differentiation of LESCs into TACs, and thereafter, into corneal epithelial cells. We also outline the evidence in support of the existence of progenitor-like cells in the cornea and whether TACs could represent a population of cells with progenitor-like capabilities within the cornea. Furthermore, to gain further insights into the dynamics of TACs in the cornea, we outline the most recent findings in other organ systems that support the hypothesis that TACs can dedifferentiate into SCs.

Abstract Background Thyroid disorders (TD) is a common complication of pegylated-interferon alpha (Peg-IFNα) therapy. Few studies have investigated the relationship between TD and the efficacy of interferon therapy for chronic hepatitis B (CHB). Therefore, we analyzed the clinical characteristics of TD in patients with CHB treated with Peg-IFNα, and evaluated the correlation between TD and Peg-IFNα treatment efficacy. Methods In this retrospective study, the clinical data of 146 patients with CHB receiving Peg-IFNα therapy were collected and analyzed. Results During the course of Peg-IFNα therapy, positive conversion of thyroid autoantibodies and TD occurred in 7.3% (85/1158) and 8.8% (105/1187) patients, respectively, and was diagnosed more often in women. The most common thyroid disorder was hyperthyroidism (53.3%), followed by subclinical hypothyroidism (34.3%). We found that thyroid function returned to normal in 78.7% of patients with CHB, and thyroid antibody levels returned to the negative range in approximately 50% of patients after interferon treatment cessation. Only 25% of patients with clinical TD required treatment. Compared with patients with hypothyroidism/subclinical hypothyroidism, patients with hyperthyroidism/subclinical hyperthyroidism showed greater reduction and seroclearance of hepatitis B surface antigen (HBsAg) levels. Conclusions TD are not an absolute contraindication for interferon therapy; however, patients should be monitored closely during interferon therapy. In pursuit of functional cure, a balance between efficacy and safety must be achieved.

Background: Millions of COVID-19 pediatric survivors are facing the risk of long COVID after recovery from acute COVID-19. The primary objective of this study was to systematically review the available literature and determine the pooled prevalence of, and risk factors for long COVID among the pediatric survivors. Methods: Studies that assessed the prevalence of, or risk factors associated with long COVID among pediatric COVID-19 survivors were systematically searched in PubMed, Embase, and Cochrane Library up to December 11th, 2022. Random effects model was performed to estimate the pooled prevalence of long COVID among pediatric COVID-19 patients. Subgroup analyses and meta-regression on the estimated prevalence of long COVID were performed by stratification with follow-up duration, mean age, sex ratio, percentage of multisystem inflammatory syndrome, hospitalization rate at baseline, and percentage of severe illness. Results: Based on 40 studies with 12,424 individuals, the pooled prevalence of any long COVID was 23.36 % ([95 % CI 15.27–32.53]). The generalized symptom (19.57 %, [95 % CI 9.85–31.52]) was reported most commonly, followed by respiratory (14.76 %, [95 % CI 7.22–24.27]), neurologic (13.51 %, [95 % CI 6.52–22.40]), and psychiatric (12.30 %, [95% CI 5.38–21.37]). Dyspnea (22.75 %, [95% CI 9.38–39.54]), fatigue (20.22 %, [95% CI 9.19–34.09]), and headache (15.88 %, [95 % CI 6.85–27.57]) were most widely reported specific symptoms. The prevalence of any symptom during 3–6, 6–12, and> 12 months were 26.41 % ([95 % CI 14.33–40.59]), 20.64 % ([95 % CI 17.06–24.46]), and 14.89 % ([95 % CI 6.09–26.51]), respectively. Individuals with aged over ten years, multisystem inflammatory syndrome, or had severe clinical symptoms exhibited higher prevalence of long COVID in multi-systems. Factors such as older age, female, poor physical or mental health, or had severe infection or more symptoms were more likely to have long COVID in pediatric survivors. Conclusions: Nearly one quarter of pediatric survivors suffered multisystem long COVID, even at 1 year after infection. Ongoing monitoring, comprehensive prevention and intervention is warranted for pediatric survivors, especially for individuals with high risk factors.

This study aimed to analyze the effect of lipid peroxidation on the allergenicity and functional properties of soybean β-conglycinin (7S) and glycinin (11S). Oxidation complexes were determined using the lipid peroxidation method. Functional properties were analyzed based on emulsifying and foaming properties. The potential allergenicity was evaluated by in vitro and in vivo methods. The results found that oxidation altered structures of the proteins and resulted in the formation of cross-linked protein polymers. The emulsion and foaming properties of the proteins were improved after oxidation. The IgE-binding capacity of 7S and 11S reduced after oxidation. KU812 cell assays showed that both histamine and IL-4 release decreased after oxidation treatment. A mouse model showed that oxidation reduced the IgE, IgG, and IgG1 levels, as well as reduced histamine and mMCP-1 release in serum, which might suppress the allergic reaction. In conclusion, the lipid peroxidation treatment likely causes changes to the functional properties of soybean, decreasing the potential allergenicity of 7S and 11S.

Background Although biologics improve the quality of life of psoriasis patients, they also impose a substantial economic burden. There is a lack of research addressing the economic and humanistic impact of biologics in China. Objective This cross-sectional investigation aims to assess the economic cost, quality of life, and patient satisfaction among individuals with psoriasis treated with biologics and non-biologics. Methods From July 2021 to December 2022, eligible patients with psoriasis were recruited through both on-site and online questionnaire completion. The questionnaires collected sociodemographic data, clinical characteristics of psoriasis, economic costs associated with treatment, and the Dermatological Life Quality Index (DLQI). Results 481 patients with a mean age of 40.8 ± 13.4 years old were included and classified into a non-biologic (n = 195) and biologic (n = 286) treatment group. The direct medical cost for non-biologics patients was 7,249 CNY, accounting for 70.0% of the total cost, while biologics patients incurred 15,176 CNY, making up 94.3% of the total cost. The non-biologic group had higher costs related to hospitalization, self-purchase of drugs, and indirect costs than the biologic treatment group. Additionally, DLQI scores were higher in the non-biologic group. Conclusion Patients in the biologic group experienced a higher economic burden and better quality of life than those in the non-biologic group.

Hepatitis B Surface Antigen (HBsAg) seroclearance is the highest treatment goal recommended by the current guidelines for hepatitis B. Levels of antibodies to HBsAg (anti-HBs) are strongly associated with HBsAg recurrence, but hepatitis B vaccination may increase the anti-HBs seroconversion rate and reduce recurrence. We conducted a retrospective clinical study to ascertain the effect of this vaccination on the seroconversion rate and levels of protective anti-HBs after HBsAg. In this retrospective study, we distributed a questionnaire through an online survey platform to collect information related to hepatitis B vaccination in patients with functional cure of hepatitis B with Interferon-α (IFNα) therapy. We enrolled 320 patients who achieved functional cure from IFNα therapy. Of these, 219 patients had received hepatitis B vaccination according to their personal preference and drug accessibility after HBsAg seroclearance, whereas the remaining 101 patients did not receive hepatitis B vaccination. The anti-HBs seroconversion rate of 78.1% in the vaccinated group was significantly greater than that in the unvaccinated group (41.6%) (p < 0.001). Stratified comparisons with anti-HBs of ≥ 100 IU/L and ≥ 300 IU/L showed that both proportions in the vaccinated group were greater than those in the unvaccinated group (71.2% vs. 32.7% and 56.2% vs. 17.8%, respectively, all p-values < 0.001). Logistic regression analysis showed that the odds ratio of vaccination was 4.427, which was the strongest influencing factor for anti-HBs, reaching 100 IU/L or higher. Hepatitis B vaccination in patients after HBsAg seroclearance not only increased the anti-HBs seroconversion rate but also significantly increased antibody levels, with good safety, indicating the clinical value of vaccine therapy for patients with functional cure.

Background To investigate the optimal radiotherapy plans for synchronous bilateral breast cancer (SBBC) patients receiving postmastectomy radiotherapy (PMRT), including regional lymph node irradiation (RNI). Methods For 10 SBBC patients who underwent bilateral mastectomy and received bilateral PMRT with RNI, 3 integrally optimized plans with a single isocenter were designed for each patient in this retrospective study: intensity-modulated radiation therapy (IMRT) with 9 fixed beams (9F-IMRT), volumetric-modulated arc therapy (VMAT) with 2 pairs of half arcs (2F-VMAT), VMAT with 2 pairs of outer tangential arcs and 1 pair of 200-degree arcs (3F-VMAT). The paired t -test (in the case of normal variables) and Friedman's test (in the case of nonnormal variables) were applied to compare the planning target volumes (PTVs) and organs at risk (OARs) values of the 3 techniques. Results The 3 techniques provided adequate target dose coverage and comparable results for PTVs. For OARs, 3F-VMAT yielded the lowest mean or median values of the left lung (15.02 ± 1.57 Gy) and right lung (14.91 ± 1.14 Gy), heart (6.19 (1.96) Gy), coronary artery (15.96 ± 5.76 Gy) and liver (8.10 ± 2.70 Gy) which were significantly different from those of 9F-IMRT and 2F-VMAT. The percentages of volume at various doses ( V 5 , V 10 , V 20 , and V 30 ) of 3F-VMAT plans were also lower than or comparable with those of 9F-IMRT and 2F-VMAT. The monitor units (MUs) of 3F-VMAT were 31% higher than those of 9F-IMRT and comparable with those of 2F-VMAT; however, there were time savings and halved beam-on times (BOTs) compared to 9F-IMRT. Conclusions The 3F-VMAT plan yielded comparable target coverage compared with 9F-IMRT and 2F-VMAT, was superior in dose sparing of normal tissues and enabled shorter BOTs, improving treatment efficiency. In our research, 3F-VMAT was the optimal radiotherapy technique for SBBC patients receiving PMRT including RNI.

BackgroundIn the era of anti-HER2 targeted therapy, the potential clinical feasibility of considering HER2-overexpressing breast cancer cases presenting with 1-3 positive axillary lymph nodes as low-risk, and thereby contemplating postoperative radiotherapy reduction, remains an important subject for in-depth examination. The aim of this retrospective study was to evaluate the effectiveness of de-escalated radiotherapy in T1-2N1M0 HER2-overexpressing breast cancer patients receiving anti-HER2 targeted therapy. Specifically, omitting regional lymph node irradiation (RNI) after breast-conserving surgery and only performing whole-breast irradiation or omitting postmastectomy radiation therapy.MethodsA retrospective analysis was conducted on 429 patients with stage T1-2N1M0 primary invasive HER2-overexpressing breast cancer from our center between 2004 and 2018. Patients who received anti-HER2 targeted therapy were divided into an RNI group and a no RNI group to assess the role of RNI. The prognostic role of RNI was investigated via the Kaplan-Meier method and Cox proportional hazards modeling.ResultsThe median follow-up time was 46.8 months (range 7.1–225.8 months). In the anti-HER2 targeted therapy group RNI yielded no significant improvements in invasive disease-free survival (IDFS) (p = 0.940), local-regional recurrence-free survival (p = 0.380), distant metastases-free survival (p = 0.698), or overall survival (p = 0.403). Estrogen receptor (ER) status (hazard ratio [HR] 0.105, 95% confidence interval [CI] 0.023–0.749, p = 0.004) and lymph vascular invasion status (LVI) (HR 5.721, 95% CI 1.586–20.633, p = 0.008) were identified as independent prognostic factors for IDFS, and ER-positive and LVI-negative patients exhibited better prognoses.ConclusionOmitting RNI may be a safe option in T1-2N1 HER2-overexpressing breast cancer patients receiving standardized anti-HER2 targeted therapy; particularly in ER-positive or LVI-negative subgroups.