HIT 2.0: an enhanced platform for Herbal Ingredients' Targets.

Literature-described targets of herbal ingredients have been explored to facilitate the mechanistic study of herbs, as well as the new drug discovery. Though several databases provided similar information, the majority of them are limited to literatures before 2010 and need to be updated urgently. HIT 2.0 was here constructed as the latest curated dataset focusing on Herbal Ingredients' Targets covering PubMed literatures 2000-2020. Currently, HIT 2.0 hosts 10 031 compound-target activity pairs with quality indicators between 2208 targets and 1237 ingredients from more than 1250 reputable herbs. The molecular targets cover those genes/proteins being directly/indirectly activated/inhibited, protein binders, and enzymes substrates or products. Also included are those genes regulated under the treatment of individual ingredient. Crosslinks were made to databases of TTD, DrugBank, KEGG, PDB, UniProt, Pfam, NCBI, TCM-ID and others. More importantly, HIT enables automatic Target-mining and My-target curation from daily released PubMed literatures. Thus, users can retrieve and download the latest abstracts containing potential targets for interested compounds, even for those not yet covered in HIT. Further, users can log into 'My-target' system, to curate personal target-profiling on line based on retrieved abstracts. HIT can be accessible at http://hit2.badd-cao.net.

Metformin-Loaded Chitosan Hydrogels Suppress Bladder Tumor Growth in an Orthotopic Mouse Model via Intravesical Administration.

Our previous study found that the intravesical perfusion of metformin has excellent inhibitory effects against bladder cancer (BC). However, this administration route allows the drug to be diluted and excreted in urine. Therefore, increasing the adhesion of metformin to the bladder mucosal layer may prolong the retention time and increase the pharmacological activity. It is well known that chitosan (Cs) has a strong adhesion to the bladder mucosal layer. Thus, this study established a novel formulation of metformin to enhance its antitumor activity by extending its retention time. In this research, we prepared Cs freeze-dried powder and investigated the effect of metformin-loaded chitosan hydrogels (MLCH) in vitro and in vivo. The results showed that MLCH had a strong inhibitory effect against proliferation and colony formation in vitro. The reduction in BC weight and the expression of tumor biomarkers in orthotopic mice showed the robust antitumor activity of MLCH via intravesical administration in vivo. The non-toxic profile of MLCH was observed as well, using histological examinations. Mechanistically, MLCH showed stronger functional activation of the AMPKα/mTOR signaling pathway compared with metformin alone. These findings aim to make this novel formulation an efficient candidate for managing BC via intravesical administration.

TRIP13 knockdown inhibits the proliferation, migration, invasion, and promotes apoptosis by suppressing PI3K/AKT signaling pathway in U2OS cells.

BACKGROUND: Although osteosarcoma (OS) is the most common malignant bone tumor, the biological mechanism underlying its incidence and improvement remains unclear. This study investigated early diagnosis and treatment objectives using bioinformatics strategies and performed experimental verification. METHODS AND RESULTS: The top 10 OS hub genes-CCNA2, CCNB1, AURKA, TRIP13, RFC4, DLGAP5, NDC80, CDC20, CDK1, and KIF20A-were screened using bioinformatics methods. TRIP13 was chosen for validation after reviewing literature. TRIP13 was shown to be substantially expressed in OS tissues and cells, according to Western blotting (WB) and quantitative real-time polymerase chain reaction data. Subsequently, TRIP13 knockdown enhanced apoptosis and decreased proliferation, migration, and invasion in U2OS cells, as validated by the cell counting kit-8 test, Hoechst 33,258 staining, wound healing assay, and WB. In addition, the levels of p-PI3K/PI3K and p-AKT/AKT in U2OS cells markedly decreased after TRIP13 knockdown. Culturing U2OS cells, in which TRIP13 expression was downregulated, in a medium supplemented with a PI3K/AKT inhibitor further reduced their proliferation, migration, and invasion and increased their apoptosis. CONCLUSIONS: TRIP13 knockdown reduced U2OS cell proliferation, migration, and invasion via a possible mechanism involving the PI3K/AKT signaling pathway.

The mechanosensory and mechanotransductive processes mediated by ion channels and the impact on bone metabolism: A systematic review.

Mechanical environments were associated with alterations in bone metabolism. Ion channels present on bone cells are indispensable for bone metabolism and can be directly or indirectly activated by mechanical stimulation. This review aimed to discuss the literature reporting the mechanical regulatory effects of ion channels on bone cells and bone tissue. An electronic search was conducted in PubMed, Embase and Web of Science. Studies about mechanically induced alteration of bone cells and bone tissue by ion channels were included. Ion channels including TRP family channels, Ca2+ release-activated Ca2+ channels (CRACs), Piezo1/2 channels, purinergic receptors, NMDA receptors, voltage-sensitive calcium channels (VSCCs), TREK2 potassium channels, calcium- and voltage-dependent big conductance potassium (BKCa) channels, small conductance, calcium-activated potassium (SKCa) channels and epithelial sodium channels (ENaCs) present on bone cells and bone tissue participate in the mechanical regulation of bone development in addition to contributing to direct or indirect mechanotransduction such as altered membrane potential and ionic flux. Physiological (beneficial) mechanical stimulation could induce the anabolism of bone cells and bone tissue through ion channels, but abnormal (harmful) mechanical stimulation could also induce the catabolism of bone cells and bone tissue through ion channels. Functional expression of ion channels is vital for the mechanotransduction of bone cells. Mechanical activation (opening) of ion channels triggers ion influx and induces the activation of intracellular modulators that can influence bone metabolism. Therefore, mechanosensitive ion channels provide new insights into therapeutic targets for the treatment of bone-related diseases such as osteopenia and aseptic implant loosening.

Targeted therapy for intervertebral disc degeneration: inhibiting apoptosis is a promising treatment strategy.

Intervertebral disc (IVD) degeneration (IDD) is a multifactorial pathological process associated with low back pain (LBP). The pathogenesis is complicated, and the main pathological changes are IVD cell apoptosis and extracellular matrix (ECM) degradation. Apoptotic cell loss leads to ECM degradation, which plays an essential role in IDD pathogenesis. Apoptosis regulation may be a potential attractive therapeutic strategy for IDD. Previous studies have shown that IVD cell apoptosis is mainly induced by the death receptor pathway, mitochondrial pathway, and endoplasmic reticulum stress (ERS) pathway. This article mainly summarizes the factors that induce IDD and apoptosis, the relationship between the three apoptotic pathways and IDD, and potential therapeutic strategies. Preliminary animal and cell experiments show that targeting apoptotic pathway genes or drug inhibition can effectively inhibit IVD cell apoptosis and slow IDD progression. Targeted apoptotic pathway inhibition may be an effective strategy to alleviate IDD at the gene level. This manuscript provides new insights and ideas for IDD therapy.

Platelet-lymphocyte ratio as a potential prognostic factor in gynecologic cancers: a meta-analysis.

PURPOSE: Cancer-related inflammation plays an important role in tumor development and progression. Platelet-lymphocyte ratio (PLR) has been studied as a biomarker for prognosis in gynecologic cancers. But, the results of previous studies were controversial, so we performed this meta-analysis. METHODS: We searched the scientific database of PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure (CNKI) using free text and MeSH keywords. Crude HR (hazard ratio) with 95% confidence interval was used to evaluate the risk association between PLR and overall survival (OS) or progression-free survival (PFS) in gynecologic neoplasms. RESULTS: There totally 23 studies, including 6869 patients who were eligible, most of which are published after 2015 or later. PLR greater than the cut-off was associated with poorer survival prognosis in ovarian cancer [OS: HR 1.80 (95% CI 1.37-2.37), p = 0.000; PFS: HR 1.63 (95% CI 1.38-1.91), p = 0.000] and cervical cancer [OS: HR 1.36 (95% CI 1.10-1.68), p = 0.005; PFS: HR 1.40 (95% CI 1.16-1.70), p = 0.002], but not in endometrial cancer [OS: HR 1.95 (95% CI 0.65-5.84), p = 0.234]. CONCLUSIONS: The current meta-analysis revealed that pretreatment PLR was a simple, promising prognostic indicator for OS and PFS in ovarian and cervical cancers. But, its significance of prognosis did not agree with endometrial neoplasm. However, due to the limited number of original studies, future large-scale studies with more well-designed, high-quality studies are still needed.

N-Methyl-4-pyridinium Tetrazolate Zwitterion-Based Photochromic Materials.

N,N'-Disubstituted bipyridinium (viologen) and N-monosubstituted bipyridinium compounds are well known for their electron-transfer (ET) photochromic behavior. Their modification has exclusively focused on the N-substituents to date. For the first time, we have studied the photochromic behavior when one pyridyl ring of the bipyridinium is substituted with a multifunctional azole group, and have found that two new coordination compounds based on N-methyl-4-pyridinium tetrazolate (mptz) zwitterion, [Zn(mptz)2 Br2 ] (1) and [Cd3 (mptz)2 Cl6 ]n ⋅4n H2 O (2), exhibit typical ET photochromic behavior owing to photoinduced ET from halogen anion to the mptz ligand. This work demonstrates a new simple, neutral photoactive molecule with electron-accepting ability, which may act as a photoactive component for materials with potential photoswitching and photocatalysis applications.

[Apoptosis of hepatocellular induced by active ingredients of Zanthoxyli Radix by Raman spectroscopy].

The apoptosis of mono-hepatocellular induced by the active ingredients of the Zanthoxyli Radix was investigated using laser Raman spectroscopy. Hepatoma cells (BEL-7404) were treated with 10 mg•L⁻¹ nitidine chloride and 3 g•L⁻¹ the extracts of Zanthoxyli Radix, respectively, then were divided into two parts, one for fluorescence staining, the other for determination of Raman spectroscopy. The acquired spectra were then processed by background elimination, smoothing, and normalization. Fluorescence staining results showed that the nucleuses from untreated group were uniformly stained, while those from the group treated for 48 hours were densely stained and broken. The spectra results revealed that the intensity of peaks associated with nucleic acid and protein decreased after the cells were incubated with the extracts of Zanthoxyli Radix for 12, 24, 36 and 48 hours. The intensity of peaks at 785,1 002,1 175,1 660 cm⁻¹ was decreased with the time of the cells were incubated by the extracts of Zanthoxyli Radix. The results indicated that the extracts of Zanthoxyli Radix could induce the apoptosis of hepatoma cells and reduce the amount of nucleic acid and protein in the cells. There is a certain relevance between the drug treatment time and the efficacy. The above results suggest that Raman spectra can provide abundant information about the changes in biological macromolecules within the cells after incubated by the extracts of Zanthoxyli Radix and serve as an effective method for the real time measurement of apoptosis.

Valence tautomeric transitions of three one-dimensional cobalt complexes.

Three novel complexes, namely, [Co(III)(3,5-DBCat)(3,5-DBSq)(bpe)]·2CH3CN·2H2O (1·S), [Co(III)(3,5-DBCat)(3,5-DBSq)(azpy)]·2CH3CN·2H2O (2·S), and [Co(II)(3,5-DBSq)2(bpb)][Co(III)(3,5-DBCat)(3,5-DBSq)(bpb)]0.5·2CH3CN·2H2O (3·S), were synthesized and characterized by valence tautomeric (VT) X-ray diffraction and magnetic measurements [where 3,5-DBCatH2 = 3,5-di-tert-butyl-catechol, 3,5-DBSqH = 3,5-di-tert-butyl-semiquinone, bpe = trans-bis(4-pyridyl)ethylene, azpy = trans-4,4'-azopyridine, and bpb = 1,4-bis(4-pyridyl)benzene]. The three complexes have similar one-dimensional chain structure building from bidentate-bridging pyridine ligands and planar 3,5-DBCat/3,5-DBSq-fixed Co(II/III) entities. Complexes 1·S and 2·S could retain the crystallinity during desolvation, and the crystal structures of 1 and 2 were therefore able to be determined. Only when 1·S and 2·S desolvated above 310 K did the magnetic susceptibilities × temperatures values of the two complexes rise sharply, and then thermally induced complete, one-step VT transitions for 1 and 2 were available and repeatable. Complex 3·S showed an incomplete, one-step VT transition independent of solvent molecules. Among these complexes, only 1 was sensitive to photoexcitation at low temperature, its photoinduced metastable state relaxed with temperature-independent behavior at low temperature range (5-10 K) and with thermally assisted behavior at high temperature range (above 20 K), respectively.

Co-ligand and solvent effects on the spin-crossover behaviors of PtS-type porous coordination polymers.

In our previous work ( Chen , X.-Y. ; Chem. Commun. 2013 , 49 , 10977 - 10979 ), we have reported the crystal structure and spin-crossover properties of a compound [Fe(NCS)2(tppm)]·S [1·S, tppm = 4,4',4″,4‴-tetrakis(4-pyridylethen-2-yl)tetraphenylmethane, S = 5CH3OH·2CH2Cl2]. Here, its analogues [Fe(X)2(tppm)]·S [X = NCSe(-), NCBH3(-), and N(CN)2(-) for compounds 2·S, 3·S, and 4·S, respectively] have been synthesized and characterized by variable-temperature X-ray diffraction and magnetic measurements. The crystal structure analyses of 2·S and 3·S reveal that both compounds possess the same topologic framework (PtS-type) building from the tetrahedral ligand tppm and planar unit FeX2; the framework is two-fold self-interpenetrated to achieve one-dimensional open channels occupied by solvent molecules. Powder X-ray diffraction study indicates the same crystal structure for 4. The average values of Fe-N distances observed, respectively, at 100, 155, and 220 K for the Fe1/Fe2 centers are 1.969/2.011, 1.970/2.052, and 2.098/2.136 Å for 2·S, whereas those at 110, 175, and 220 K are 1.972/2.013, 1.974/2.056, and 2.100/2.150 Å for 3·S, indicating the presence of a two-step spin crossover in both compounds. Temperature-dependent magnetic susceptibilities (χMT) confirm the two-step spin-crossover behavior at 124 and 200 K in 2·S, 151 and 225 K in 3·S, and 51 and 126 K in 4·S, respectively. The frameworks of 2-4 are reproducible upon solvent exchange and thereafter undergo solvent-dependent spin-crossover behaviors.

Radioactive iodine therapy for thyroid cancer coexisting with hashimoto's thyroiditis: a systematic review and meta-analysis.

OBJECTIVES: To investigate the clinical character of differentiated thyroid cancer (DTC) coexisting with Hashimoto's thyroiditis (HT) and provide state-of-art evidence for personalized RAIT for patients coexisting with HT. METHODS: From January 2000 to January 2023, PubMed, Embase, Web of Science databases were searched for relevant original articles that published in English on the RAIT efficacy for DTC with HT. Revman 5.4 and Stata 17.0 were used for date analysis. RESULTS: Eleven studies involved 16,605 DTC patients (3,321 with HT) were included. HT were more frequent in female (OR: 2.90, 95% CI: 1.77 to 4.76, P < 0.00001). The size of tumor (MD: -0.20, 95% CI: -0.30 to -0.11), extrathyroidal extension rate (OR: 0.77, 95% CI: 0.67 to 0.90) and metastasis rate (OR: 0.18, 95% CI: 0.08 to 0.41) were less in HT, but TNM stage had no significant difference among HT and non-HT group. DFS rate (OR: 1.96, 95% CI : 1.57 to 2.44, P < 0.00001), 5-year and 10-year DFS (OR: 1.73, 95% CI: 1.04 to 2.89, P = 0.04; OR: 1.56, 95% CI: 1.17 to 2.09, P = 0.003, respectively) were higher in HT group. The recurrent (OR: 0.62, 95% CI: 0.45 to 0.83, P = 0.002), RAIT dosage (MD=-38.71, 95% CI: -60.86 to -16.56, P = 0.0006) and treatment (MD: -0.13, 95% CI: -0.22 to -0.03, P = 0.008) were less in HT group. CONCLUSIONS: DTC coexisting with HT was associated with less invasion. DFS of HT group was higher than non-HT group after RAIT. Low dose treatment did not impair the efficacy of RAIT in DTC with HT. ADVANCES IN KNOWLEDGE: Hashimoto's thyroiditis is a risk for DTC, but it minimalizes the progression of cancer and enhance the efficacy of RAIT, which should be considered in personalizing RAIT.

Tetrahedral framework nucleic acid-based small-molecule inhibitor delivery for ecological prevention of biofilm.

Biofilm formation constitutes the primary cause of various chronic infections, such as wound infections, gastrointestinal inflammation and dental caries. While preliminary achievement of biofilm inhibition is possible, the challenge lies in the difficulty of eliminating the bactericidal effects of current drugs that lead to microbiota imbalance. This study, utilizing in vitro and in vivo models of dental caries, aims to efficiently inhibit biofilm formation without inducing bactericidal effects, even against pathogenic bacteria. The tetrahedral framework nucleic acid (tFNA) was employed as a delivery vector for a small-molecule inhibitor (smI) specifically targeting the activity of glucosyltransferases C (GtfC). It was observed that tFNA loaded smI in a small-groove binding manner, efficiently transferring it into Streptococcus mutans, thereby inhibiting GtfC activity and extracellular polymeric substances formation without compromising bacterial survival. Furthermore, smI-loaded tFNA demonstrated a reduction in the severity of dental caries in vivo without adversely affecting oral microbial diversity and exhibited desirable topical and systemic biosafety. This study emphasizes the concept of 'ecological prevention of biofilm', which is anticipated to advance the optimization of biofilm prevention strategies and the clinical application of DNA nanocarrier-based drug formulations.

Burnout Prevalence and Associated Factors Among Palliative and Hospice Care Professionals During the COVID-19 Endemic: An Exploratory Survey.

BACKGROUND: Burnout is a significant issue for palliative and hospice professionals, exacerbated by the impact of Coronavirus Disease 2019 (COVID-19) on healthcare professionals. It is crucial to update our understanding of prevalence data, identify associated factors, and evaluate support resources during the COVID-19 pandemic. METHODS: We aimed to explore the prevalence of burnout among palliative and hospice care workers, 2 years into the COVID-19 pandemic by using the Maslach's Burnout Inventory; anxiety, using General Anxiety Disorder-7 (GAD-7), workload, risk perception of COVID-19, confidence in protective measures (personal, workplace, and government), and usage and perceived helpfulness of support resources. Univariate logistic regression analysis was conducted to analyse burnout against these factors. RESULTS: Of the 115 respondents encompassing doctors, nurses and social workers (76.5% female; average age 40.9), 48.7% experienced burnout. Burnout correlated with increased anxiety, higher COVID-19 risk perception, heavier workload, and reduced confidence in protective measures. Peer support, COVID information, and psychological programs were rated as the most effective for coping. CONCLUSION: The study indicates considerable levels of burnout among palliative and hospice care workers, linked to workload, anxiety, and perceived risk. Traditional mental health interventions had limited efficacy; respondents favoured peer support and organisational changes. The findings stress the need for a holistic approach, including diverse resources, workload management, and regular mental health assessments.

Artificial intelligence in liver imaging: methods and applications.

Liver disease is regarded as one of the major health threats to humans. Radiographic assessments hold promise in terms of addressing the current demands for precisely diagnosing and treating liver diseases, and artificial intelligence (AI), which excels at automatically making quantitative assessments of complex medical image characteristics, has made great strides regarding the qualitative interpretation of medical imaging by clinicians. Here, we review the current state of medical-imaging-based AI methodologies and their applications concerning the management of liver diseases. We summarize the representative AI methodologies in liver imaging with focusing on deep learning, and illustrate their promising clinical applications across the spectrum of precise liver disease detection, diagnosis and treatment. We also address the current challenges and future perspectives of AI in liver imaging, with an emphasis on feature interpretability, multimodal data integration and multicenter study. Taken together, it is revealed that AI methodologies, together with the large volume of available medical image data, might impact the future of liver disease care.

The walnut-derived peptide TW-7 improves mouse parthenogenetic embryo development of vitrified MII oocytes potentially by promoting histone lactylation.

BACKGROUND: Previous studies have shown that the vitrification of metaphase II (MII) oocytes significantly represses their developmental potential. Abnormally increased oxidative stress is the probable factor; however, the underlying mechanism remains unclear. The walnut-derived peptide TW-7 was initially isolated and purified from walnut protein hydrolysate. Accumulating evidences implied that TW-7 was a powerful antioxidant, while its prospective application in oocyte cryopreservation has not been reported. RESULT: Here, we found that parthenogenetic activation (PA) zygotes derived from vitrified MII oocytes showed elevated ROS level and delayed progression of pronucleus formation. Addition of 25 µmol/L TW-7 in warming, recovery, PA, and embryo culture medium could alleviate oxidative stress in PA zygotes from vitrified mouse MII oocytes, furtherly increase proteins related to histone lactylation such as LDHA, LDHB, and EP300 and finally improve histone lactylation in PA zygotes. The elevated histone lactylation facilitated the expression of minor zygotic genome activation (ZGA) genes and preimplantation embryo development. CONCLUSIONS: Our findings revealed the mechanism of oxidative stress inducing repressed development of PA embryos from vitrified mouse MII oocytes and found a potent and easy-obtained short peptide that could significantly rescue the decreased developmental potential of vitrified oocytes, which would potentially contribute to reproductive medicine, animal protection, and breeding.

ISR inhibition reverses pancreatic ß-cell failure in Wolfram syndrome models.

Pancreatic ß-cell failure by WFS1 deficiency is manifested in individuals with wolfram syndrome (WS). The lack of a suitable human model in WS has impeded progress in the development of new treatments. Here, human pluripotent stem cell derived pancreatic islets (SC-islets) harboring WFS1 deficiency and mouse model of ß cell specific Wfs1 knockout were applied to model ß-cell failure in WS. We charted a high-resolution roadmap with single-cell RNA-seq (scRNA-seq) to investigate pathogenesis for WS ß-cell failure, revealing two distinct cellular fates along pseudotime trajectory: maturation and stress branches. WFS1 deficiency disrupted ß-cell fate trajectory toward maturation and directed it towards stress trajectory, ultimately leading to ß-cell failure. Notably, further investigation of the stress trajectory identified activated integrated stress response (ISR) as a crucial mechanism underlying WS ß-cell failure, characterized by aberrant eIF2 signaling in WFS1-deficient SC-islets, along with elevated expression of genes in regulating stress granule formation. Significantly, we demonstrated that ISRIB, an ISR inhibitor, efficiently reversed ß-cell failure in WFS1-deficient SC-islets. We further validated therapeutic efficacy in vivo with ß-cell specific Wfs1 knockout mice. Altogether, our study provides novel insights into WS pathogenesis and offers a strategy targeting ISR to treat WS diabetes.

Preparation and Properties of a Novel Biodegradable Composite Hydrogel Derived from Gelatin/Chitosan and Polylactic Acid as Slow-Release N Fertilizer.

To improve the efficient use of nitrogen and decrease the environmental pollution of N losses, a novel and biodegradable composite hydrogel was prepared by chemical cross-linking synthesis using gelatin (Gel), chitosan (CS) and polylactic acid (PLA) as raw materials. Urea as the nitrogen source was loaded into this new biodegradable hydrogel using the solution immersion method. The chemical structures of the composite hydrogels were characterized and their properties were analyzed by XRD and XPS. The regulation of urea loading and the swelling behavior of the composite hydrogel under different temperature conditions were investigated; the release behavior and release model of the composite hydrogel in the aqueous phase was explored. The results show that the loading of urea is controllable in aqueous urea solution with different concentrations. In the water phase, it shows a three-stage sustained release behavior, that is, the initial release rate of urea is relatively fast, and the medium release rate of urea gradually slows down, and finally the nutrient release rate tends to be flat. The release behavior in the water phase fits to the Ritger-Peppas model. Within 10 min, 180 min and 900 min, the cumulative nutrient release rate of gelatin/chitosan/PLA-urea (GCPU) composite hydrogel is 20%, 70% and 86%, respectively. Compared with pure urea, The urea diffusion time of GCPU was extended by 1350-times. In addition, the GCPU also has good water absorption and water retention properties, in which average water content can reach as high as 4448%. All of the results in this work showed that GCPU hydrogel had good water absorption and retention and N slow-release properties, which are expected to be widely used in sustainable agriculture and forestry, especially in arid and degraded land.

Nanoscale Treatment of Intervertebral Disc Degeneration: Mesenchymal Stem Cell Exosome Transplantation.

A common surgical disease, intervertebral disc degeneration (IVDD), is increasing at an alarming rate in younger individuals. Repairing damaged intervertebral discs (IVDs) and promoting IVD tissue regeneration at the molecular level are important research goals.Exosomes are extracellular vesicles (EVs) secreted by cells and can be derived from most body fluids. Mesenchymal stem cell-derived exosomes (MSC-exos) have characteristics similar to those of the parental MSCs. These EVs can shuttle various macromolecular substances, such as proteins, messenger RNAs (mRNAs), and microRNAs (miRNAs) and regulate the activity of recipient cells through intercellular communication. Reducing inflammation and apoptosis can significantly promote IVD regeneration to facilitate the repair of the IVD. Compared with MSCs, exosomes are more convenient to store and transport, and the use of exosomes can prevent the risk of rejection with cell transplantation. Furthermore, MSC-exo-mediated treatment may be safer and more effective than MSC transplantation. In this review, we summarize the use of bone marrow mesenchymal stem cells (BMSCs), adipose-derived mesenchymal stem cells (AMSCs), nucleus pulposus mesenchymal stem cells (NPMSCs), and stem cells from other sources for tissue engineering and use in IVDD. Here, we aim to describe the role of exosomes in inhibiting IVDD, their potential therapeutic effects, the results of the most recent research, and their clinical application prospects to provide an overview for researchers seeking to explore new treatment strategies and improve the efficacy of IVDD treatment.

Charting a high-resolution roadmap for regeneration of pancreatic ß cells by in vivo transdifferentiation from adult acinar cells.

Adult mammals have limited capacity to regenerate functional cells. Promisingly, in vivo transdifferentiation heralds the possibility of regeneration by lineage reprogramming from other fully differentiated cells. However, the process of regeneration by in vivo transdifferentiation in mammals is poorly understood. Using pancreatic ß cell regeneration as a paradigm, we performed a single-cell transcriptomic study of in vivo transdifferentiation from adult mouse acinar cells to induced ß cells. Using unsupervised clustering analysis and lineage trajectory construction, we uncovered that the cell fate remodeling trajectory was linear at the initial stage and the reprogrammed cells either evolved to induced ß cells or toward a "dead-end" state after day 4.Moreover, functional analyses identified both p53 and Dnmt3a that acted as reprogramming barriers during the process of in vivo transdifferentiation. Collectively, we decipher a high-resolution roadmap of regeneration by in vivo transdifferentiation and provide a detailed molecular blueprint to facilitate mammalian regeneration.

Shareholder personal risk and firm risk: An empirical analysis of share pledges and firm debt policies.

The impact of personal risk caused by controlling shareholders' equity pledges on the company's debt policy is an issue worth exploring. Using Chinese A-share listed companies from 2006 to 2020, this paper studies the impact of ultimate owner equity pledges on firm debt size and debt maturity structure and explores the mechanism of ultimate owner personal leverage on firms. The results show that the increase in ultimate owner stock pledges leads to higher financial leverage and a longer debt maturity structure for the company. In addition, the study reveals that the high personal leverage of the ultimate owner of the pledged equity is an influential mechanism driving the transfer of personal risk to the firm. In particular, even if a company's actual debt ratio is higher than its target debt ratio, equity pledges can prompt listed companies to increase their debt ratios and debt maturities, causing them to take on excessive debt risk and transfer the risk to creditors. It follows that the tunneling effect is a driving force of equity pledging and corporate debt policies. These results remain robust after the robustness test and endogenous test. The conclusions of this paper not only emphasize the impact of shareholders' personal risk on the firm but also provide a reference for investors' perception of firm risk.