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One of the crucial issues confronting China is high carbon dioxide (CO2) emissions. Despite the numerous measures outlined to promote the country’s carbon neutrality target, CO2 emissions in the nation continue to increase. This means that more policy options are needed to help improve environmental sustainability (ES) in the nation. Hence, examining the relationship between financial development (FD), foreign direct investment, industrialization, and environmental sustainability in China to provide proper recommendations to drive the carbon neutrality agenda of the nation is deemed fitting. In attaining this goal, time-series data from the period 1990 to 2018 is employed. According to the results, foreign direct investment deteriorates environmental sustainability by promoting more CO2 emissions. This validates the pollution haven hypothesis (PHH). In addition, industrialization and financial development are not friendly to the nation’s environmental quality. Furthermore, economic growth and urbanization escalate environmental pollution in the nation. In addition, the interactions between financial development and foreign direct investment and between financial development and industrialization deteriorate the environment in China. Moreover, foreign direct investment and financial development have an inverted U-shaped association with environmental degradation, but industrialization and environmental pollution are not nonlinearly related. The study advocated for the implementation of measures that could help advance the carbon-neutrality targets of the nation.

PurposeInvestigate the clinical/hematological characteristics of children infected with the Omicron variant of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and identify an effective indicator to distinguish coronavirus disease 2019 (COVID-19) severity in children.MethodsA retrospective study was conducted through electronic medical records from pediatric patients. The demographic, clinical, and routine blood test (RBT) features of children diagnosed by real-time PCR for SARS-CoV-2 were collected.ResultsData of 261 patients were analyzed. The most common abnormality shown by RBTs was increased monocyte count (68%). Children had “mild-moderate” or “severe” forms of COVID-19. Prevalence of abnormal neutrophil count (p = 0.048), eosinophil count (p = 0.006), mean corpuscular volume (p = 0.033), mean platelet volume (p = 0.006), platelet-large cell ratio (p = 0.043), and red blood cell distribution width-standard deviation (p = 0.031) were significantly different in the two types. A combination of the neutrophil: lymphocyte ratio (NLR) and eosinophil count for diagnosing severe COVID-19 presented the largest AUC (0.688, 95% CI = 0.599–0.777; p

ObjectiveTo develop a CT-based nomogram to predict the response of advanced esophageal squamous cell carcinoma (ESCC) to neoadjuvant chemotherapy plus immunotherapy.MethodsIn this retrospective study, 158 consecutive patients with advanced ESCC receiving contrast-enhanced CT before neoadjuvant chemotherapy plus immunotherapy were randomized to a training cohort (TC, n = 121) and a validation cohort (VC, n = 37). Response to treatment was assessed with response evaluation criteria in solid tumors. Patients in the TC were divided into the responder (n = 69) and non-responder (n = 52) groups. For the TC, univariate analyses were performed to confirm factors associated with response prediction, and binary analyses were performed to identify independent variables to develop a nomogram. In both the TC and VC, the nomogram performance was assessed by area under the receiver operating characteristic curve (AUC), calibration slope, and decision curve analysis (DCA).ResultsIn the TC, univariate analysis showed that cT stage, cN stage, gross tumor volume, gross volume of all enlarged lymph nodes, and tumor length were associated with the response (all P < 0.05). Binary analysis demonstrated that cT stage, cN stage, and tumor length were independent predictors. The independent factors were imported into the R software to construct a nomogram, showing the discriminatory ability with an AUC of 0.813 (95% confidence interval: 0.735–0.890), and the calibration curve and DCA showed that the predictive ability of the nomogram was in good agreement with the actual observation.ConclusionThis study provides an accurate nomogram to predict the response of advanced ESCC to neoadjuvant chemotherapy plus immunotherapy.

B cells and the humoral immunity are important players in the pathogenesis of autoimmune diseases. BAFF (also known as BLYS) and a proliferation-inducing ligand APRIL are required for the maintenance of the B-cell pool and humoral immunity. BAFF and APRIL can promote B-cell differentiation, maturation, and plasma cell antibody secretion. BAFF/APRIL overexpression has been identified in several autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, IgA nephropathy, etc. Telitacicept, a novel fully human TACI-Fc fusion protein that binds both BAFF and APRIL, was approved in China in March 2021 for the treatment of systemic lupus erythematosus at a recommended dose of 160 mg/w subcutaneously and is in clinical trials for the treatment of multiple indications in other autoimmune diseases. In this review, we explored telitacicept’s mechanism of action and clinical data. In addition, the immune features of autoimmune nephropathy were discussed, emphasizing lupus nephritis, IgA nephropathy, and membranous nephropathy.

Macrophage infiltration into adipose tissue is a key pathological factor inducing adipose tissue dysfunction and contributing to obesity-induced inflammation and metabolic disorders. In this review, we aim to present the most recent research on macrophage heterogeneity in adipose tissue, with a focus on the molecular targets applied to macrophages as potential therapeutics for metabolic diseases. We begin by discussing the recruitment of macrophages and their roles in adipose tissue. While resident adipose tissue macrophages display an anti-inflammatory phenotype and promote the development of metabolically favorable beige adipose tissue, an increase in pro-inflammatory macrophages in adipose tissue has negative effects on adipose tissue function, including inhibition of adipogenesis, promotion of inflammation, insulin resistance, and fibrosis. Then, we presented the identities of the newly discovered adipose tissue macrophage subtypes (e.g. metabolically activated macrophages, CD9+ macrophages, lipid-associated macrophages, DARC+ macrophages, and MFehi macrophages), the majority of which are located in crown-like structures within adipose tissue during obesity. Finally, we discussed macrophage-targeting strategies to ameliorate obesity-related inflammation and metabolic abnormalities, with a focus on transcriptional factors such as PPARγ, KLF4, NFATc3, and HoxA5, which promote macrophage anti-inflammatory M2 polarization, as well as TLR4/NF-κB-mediated inflammatory pathways that activate pro-inflammatory M1 macrophages. In addition, a number of intracellular metabolic pathways closely associated with glucose metabolism, oxidative stress, nutrient sensing, and circadian clock regulation were examined. Understanding the complexities of macrophage plasticity and functionality may open up new avenues for the development of macrophage-based treatments for obesity and other metabolic diseases.

Ectopic secretion of parathyroid hormone (PTH) is a rare cause of hypercalcemia in malignancy patients. A 56-year-old woman with life-threatening hypercalcemia was caused by poorly-differentiated endometrial carcinoma secreting PTH with concomitant nodular goiter mimic parathyroid tumors. The elevated level of PTH and calcium decreased immediately after cytoreductive surgery (CRS). The pathology confirmed mismatch repair (MMR)-deficient endometrial carcinoma with PTH expression. The patient received four-course chemotherapy and one-course immunotherapy after CRS. The disease progression led to multiple organ failure and death about five months after CRS. To our knowledge, this is the first case of hypercalcemia caused by MMR-deficient endometrial carcinoma with ectopic PTH secreting and the first report of malignancy associated hypercalcemia complicated with nodular goiter.

PurposeTo determine whether gross tumor volume (GTV) of adenocarcinoma of esophagogastric junction (AEG) corresponding to cT and cN stages measured on CT could help quantitatively determine resectability.Materials and methods343 consecutive patients with AEG, including 279 and 64 randomly enrolled in training cohort (TC) and validation cohort (VC), respectively, underwent preoperative contrast-enhanced CT. Univariate and multivariate analyses for TC were performed to determine factors associated with resectability. Receiver operating characteristic (ROC) analyses were to determine if GTV corresponding to cT and cN stages could help determine resectability. For VC, Cohen’s Kappa tests were to assess performances of the ROC models.ResultscT stage, cN stage and GTV were independently associated with resectability of AEG with odds ratios of 4.715, 4.534 and 1.107, respectively. For differentiating resectable and unresectable AEG, ROC analyses showed that cutoff GTV of 32.77 cm3 in stage cT1-4N0-3 with an area under the ROC curve (AUC) of 0.901. Particularly, cutoffs of 27.67 and 32.77 cm3 in stages cT3 and cT4 obtained AUC values of 0.860 and 0.890, respectively; and cutoffs of 27.09, 33.32 and 37.39 cm3 in stages cN1, cN2 and cN3 obtained AUC values of 0.852, 0.821 and 0.902, respectively. In VC, Cohen’s Kappa tests verified that the ROC models had good performance in distinguishing between resectable and unresectable AEG (all Cohen’s K values > 0.72).ConclusionsGTV, cT and cN stages could be independent determinants of resectability of AEG. And GTV corresponding to cT and cN stages can help quantitatively determine resectability.

Ginseng is an important medicinal plant benefiting human health for thousands of years. Root disease is the main cause of ginseng yield loss. It is difficult to detect ginseng root disease by manual observation on the changes of leaves, as it takes a long time until symptoms appear on leaves after the infection on roots. In order to detect root diseases at early stages and limit their further spread, an efficient and non-destructive testing (NDT) method is urgently needed. Hyperspectral remote sensing technology was performed in this study to discern whether ginseng roots were diseased. Hyperspectral reflectance of leaves at 325-1,075 nm were collected from the ginsengs with no symptoms on leaves at visual. These spectra were divided into healthy and diseased groups according to the symptoms on roots after harvest. The hyperspectral data were used to construct machine learning classification models including random forest, extreme random tree (ET), adaptive boosting and gradient boosting decision tree respectively to identify diseased ginsengs, while calculating the vegetation indices and analyzing the region of specific spectral bands. The precision rates of the ET model preprocessed by savitzky golay method for the identification of healthy and diseased ginsengs reached 99% and 98%, respectively. Combined with the preliminary analysis of band importance, vegetation indices and physiological characteristics, 690-726 nm was screened out as a specific band for early detection of ginseng root diseases. Therefore, underground root diseases can be effectively detected at an early stage by leaf hyperspectral reflectance. The NDT method for early detection of ginsengs root diseases is proposed in this study. The method is helpful in the prevention and control of root diseases of ginsengs to prevent the reduction of ginseng yield.

PurposeTo develop and validate a quantitative model based on gross tumor volume (GTV) of gastric adenocarcinoma (GA) corresponding to N-stage measured at multidetector computed tomography (CT) for preoperative determination of resectabilityMaterials and methods493 consecutive patients with confirmed GA undergoing contrast-enhanced CT two weeks before treatments were randomly enrolled into the training cohort (TC, n = 271), internal validation cohort (IVC, n = 107) and external validation cohort (EVC, n = 115). GTV was measured on CT by multiplying sums of all tumor areas by section thickness. In TC, univariate and multivariate analyses were performed to select factors associated with resectability. Receiver operating characteristic (ROC) analysis was to determine if N-stage based GTV could identify resectability. In IVC and EVC, unweighted Cohen’s Kappa tests were to evaluate performances of the ROC models.ResultsAccording to univariate analysis, age, cT stage, cN stage and GTV were related to resectability in TC (all P-values < 0.05), and multivariate analysis suggested that cN stage and GTV were independent risk factors with odds ratios of 1.594 (95% confidence interval [CI]: 1.105–2.301) and 1.055 (95%CI: 1.035–1.076), respectively. ROC analysis in TC revealed the cutoffs of 21.81, 21.70 and 36.93 cm3 to differentiate between resectable and unresectable cancers in stages cN0-3, cN2 and cN3 with areas under the curves of more than 0.8, respectively, which was validated in IVC and EVC with average Cohen k-values of more than 0.72.ConclusionsGTV and cN stage can be independent risk factors of unresectable GA, and N-stage based GTV can help determine resectability.

Chronic low-grade inflammation in adipose tissue (AT) is a hallmark of obesity and contributes to various metabolic disorders, such as type 2 diabetes and cardiovascular diseases. Inflammation in ATs is characterized by macrophage infiltration and the activation of inflammatory pathways mediated by NF-κB, JNK, and NLRP3 inflammasomes. Adipokines, hepatokines and myokines — proteins secreted from AT, the liver and skeletal muscle play regulatory roles in AT inflammation via endocrine, paracrine, and autocrine pathways. For example, obesity is associated with elevated levels of pro-inflammatory adipokines (e.g., leptin, resistin, chemerin, progranulin, RBP4, WISP1, FABP4, PAI-1, Follistatin-like1, MCP-1, SPARC, SPARCL1, and SAA) and reduced levels of anti-inflammatory adipokines such as adiponectin, omentin, ZAG, SFRP5, CTRP3, vaspin, and IL-10. Moreover, some hepatokines (Fetuin A, DPP4, FGF21, GDF15, and MANF) and myokines (irisin, IL-6, and DEL-1) also play pro- or anti-inflammatory roles in AT inflammation. This review aims to provide an updated understanding of these organokines and their role in AT inflammation and related metabolic abnormalities. It serves to highlight the molecular mechanisms underlying the effects of these organokines and their clinical significance. Insights into the roles and mechanisms of these organokines could provide novel and potential therapeutic targets for obesity-induced inflammation.

Epigenetic regulations on the maintenance of neural stem cells (NSCs) are complicated and far from been fully understood. Our previous findings have shown that after blocking Notch signaling in NSCs in vivo, the stemness of NSCs decreases, accompanied by the downregulated expression of miR-582-5p. In the current study, we further investigated the function and mechanism of miR-582-5p in the maintenance of NSCs in vitro and in vivo. After transfecting a mimic of miR-582-5p, the formation of neurospheres and proliferation of NSCs and intermediate progenitor cells (NS/PCs) were enhanced, and the expression of stemness markers such as Sox2, Nestin, and Pax6 also increased. The results were reversed after transfection of an inhibitor of miR-582-5p. We further generated miR-582 knock-out (KO) mice to investigate its function in vivo, and we found that the number of NSCs in the subventricular zone (SVZ) region decreased and the number of neuroblasts increased in miR-582 deficient mice, indicating reduced stemness and enhanced neurogenesis of NSCs. Moreover, RNA-sequencing and molecular biological analysis revealed that miR-582-5p regulates the stemness and proliferation of NSCs by inhibiting secretory protein FAM19A1. In summary, our research uncovered a new epigenetic mechanism that regulates the maintenance of NSCs, therefore providing novel targets to amplify NSCs in vitro and to promote neurogenesis in vivo during brain pathology and aging.

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a malignancy characterized by the aberrant accumulation of immature B-cell precursors in bone marrow and other lymphoid organs. Although several intrinsic regulatory signals participating in BCP-ALL have been clarified, detailed intrinsic and extrinsic mechanisms that regulate BCP-ALL progression have not been fully understood. In the current study, we report that miR-582 is downregulated in BCP-ALL cells compared with normal B cells. Forced overexpression of miR-582 attenuated BCP-ALL cell proliferation and survival. We found that miR-582 overexpression disturbed the mitochondrial metabolism of BCP-ALL cells, leading to less ATP but more ROS production. Mechanistically, we identified PPTC7 as a direct target of miR-582. MiR-582 overexpression inhibited the activity of CoQ10, which is downstream of PPTC7 and played an important positive regulatory role in mitochondrial electron transportation. Finally, we found that overexpression of miR-582 upregulated the expression of immune checkpoint molecule CD276 and reduced NK cell-mediated cytotoxicity against BCP-ALL cells. CD276 blockade significantly increased NK cell-mediated cytotoxicity against miR-582-overexpressing BCP-ALL cells. Together, our research demonstrates that miR-582 acts as a negative regulator of BCP-ALL cells by reducing proliferation and survival, but protects BCP-ALL cells from NK cell-mediated cytotoxicity, suggesting that miR-582 may be a new therapeutic biomarker for BCP-ALL with CD276 blocker.

ObjectiveTo investigate relationship of tumor stage-based gross tumor volume (GTV) of esophageal squamous cell carcinoma (ESCC) measured on computed tomography (CT) with early recurrence (ER) after esophagectomy.Materials and MethodsTwo hundred and four consecutive patients with resectable ESCC including 159 patients enrolled in the training cohort (TC) and 45 patients in validation cohort (VC) underwent contrast-enhanced CT less than 2 weeks before esophagectomy. GTV was retrospectively measured by multiplying sums of all tumor areas by section thickness. For the TC, univariate and multivariate analyses were performed to determine factors associated with ER. Mann-Whitney U test was conducted to compare GTV in patients with and without ER. Receiver operating characteristic (ROC) analysis was performed to determine if tumor stage-based GTV could predict ER. For the VC, unweighted Cohen’s Kappa tests were used to evaluate the performances of the previous ROC predictive models.ResultsER occurred in 63 of 159 patients (39.6%) in the TC. According to the univariate analysis, histologic differentiation, cT stage, cN stage, and GTV were associated with ER after esophagectomy (all P-values < 0.05). Multivariate analysis revealed that cT stage and GTV were independent risk factors with hazard ratios of 3.382 [95% confidence interval (CI): 1.533–7.459] and 1.222 (95% CI: 1.125–1.327), respectively (all P-values < 0.05). Mann-Whitney U tests showed that GTV could help differentiate between ESCC with and without ER in stages cT1-4a, cT2, and cT3 (all P-values < 0.001), and the ROC analysis demonstrated the corresponding cutoffs of 13.31, 17.22, and 17.83 cm3 with areas under the curve of more than 0.8, respectively. In the VC, the Kappa tests validated that the ROC predictive models had good performances for differentiating between ESCC with and without ER in stages cT1-4a, cT2, and cT3 with Cohen k of 0.696 (95% CI, 0.498–0.894), 0.733 (95% CI, 0.386–1.080), and 0.862 (95% CI, 0.603–1.121), respectively.ConclusionGTV and cT stage can be independent risk factors of ER in ESCC after esophagectomy, and tumor stage-based GTV measured on CT can help predict ER.

As chemical analysis for quality control (QC) of traditional Chinese medicine (TCM) formula is difficult to guarantee the effectiveness, a bioassay method that combines QC with evaluation of therapeutic effects has been developed to assess the TCM quality. Here, we chose a thirteen-component TCM formula, Lianhua Qingwen capsule (LHQW), as a representative sample, to explore the pivotal biomarkers for a bioassay and to investigate close association between QC and pharmacological actions. Initially, our results showed that chemical fingerprinting could not effectively distinguish batches of LHQW. Pharmacological experiments indicated that LHQW could treat influenza A virus (H1N1) infection in the H1N1 mouse model, as claimed in clinical trials, by improving pathologic alterations and bodyweight loss, and decreasing virus replication, lung lesions and inflammation. Furthermore, by using serum metabolomics analysis, we identified two important metabolites, prostaglandin F2α and arachidonic acid, and their metabolic pathway, arachidonic acid metabolism, as vital indicators of LHQW in treatment of influenza. Subsequently, macrophages transcriptomics highlighted the prominent role of cyclooxygenase-2 (COX-2) as the major rate-limiting enzyme in the arachidonic acid metabolism pathway. Finally, COX-2 was validated by in vivo gene expression and in vitro enzymatic activity with 43 batches of LHQW as a viable pharmacological biomarker for the establishment of bioassay-based QC. Our study provides systematic methodology in the pharmacological biomarker exploration for establishing the bioassay-based QC of LHQW or other TCM formulas relating to their pharmacological activities and mechanism.

Novel inhibitors are urgently needed for use as targeted therapies to improve the overall survival (OS) of patients with ovarian cancer. Here, we show that cell division cycle 25B (CDC25B) is over-expressed in ovarian tumors and associated with poor patient prognosis. All previously reported CDC25B inhibitors have been identified by their ability to reversibly inhibit the catalytic dephosphorylation activity of CDC25B in vitro; however, none of these compounds have entered clinical trials for ovarian cancer therapy. In this study, we synthesized a novel small molecule compound, WG-391D, that potently down-regulates CDC25B expression without affecting its catalytic dephosphorylation activity. The inhibition of CDC25B by WG-391D is irreversible, and WG-391D should therefore exhibit potent antitumor activity against ovarian cancer. WG-391D induces cell cycle progression arrest at the G2/M phase. Half maximal inhibitory concentration (IC50) values of WG-391D for inhibition of the proliferation and migration of eight representative ovarian cancer cell lines (SKOV3, ES2, OVCAR8, OVTOKO, A2780, IGROV1, HO8910PM, and MCAS) and five primary ovarian tumor cell lines (GFY004, GFY005, CZ001, CZ006, and CZ008) were lower than 10 and 1 μM, respectively. WG-391D inhibited tumor growth in nude mice inoculated with SKOV3 cells or a patient-derived xenograft (PDX). The underlying mechanisms were associated with the down-regulation of CDC25B and subsequent inactivation of cell division cycle 2 (CDC2) and the serine/threonine kinase, AKT. In conclusion, this study demonstrates that WG-391D exhibits strong antitumor activity against ovarian cancer and indicates that the down-regulation of CDC25B by inhibitors could provide a rationale for ovarian cancer therapy.

Currently, numerous liver injury cases related to a famous Chinese herb- Polygonum Multiflorum (Heshouwu in Chinese) have attracted great attention in many countries. Our previous work showed that Heshouwu-induced hepatotoxicity belonged to idiosyncratic drug-induced liver injury (IDILI). Unfortunately, the components and mechanisms attributed to IDILI of Heshouwu are difficult to determine and thus remain unknown. Attempts to explore puzzles, we prepared the chloroform (CH)-, ethyl acetate (EA)-, and residue (RE) extracts of Heshouwu to investigate IDILI constituents and underlying mechanisms，using biochemistry, histopathology, and metabolomics examinations. The results showed that co-treatment with non-toxic dose of lipopolysaccharide (LPS) and EA extract could result in evident liver injury, indicated by the significant elevation of plasma alanine aminotransferase (ALT)and aspartate aminotransferase (AST) activities, as well as obvious liver histologic damage; whereas other two separated fractions, CH and RE extracts, failed to induce observable liver injury. Furthermore, 21 potential metabolomic biomarkers that differentially expressed in LPS/EA group compared with other groups without liver injury were identified by untargeted metabolomics, mainly involved two pathways: tricarboxylic acid cycle and sphingolipid metabolism. This work illustrated EA extract had close association with the idiosyncratic hepatotoxicity of Heshouwu and provided a metabolomic insight into IDILI of different extracts from Heshouwu.

The hepatotoxicity induced by Polygoni Multiflori Radix Praeparata (PM) has been worldwide reported. Hence, it is worthwhile to find herbs with detoxification based on the compatibility of traditional Chinese medicine. In this work, rat model with PM/LPS-stimulated idiosyncratic liver injury was used. The effects of Poria, Licorice and Panax notoginseng on rats of PM/LPS-induced liver injury were investigated, respectively, hoping to find the most effective herbal medicine to reduce the hepatotoxicity. The biochemical and histological tests showed that PM induced the idiosyncratic hepatotoxicity of rats with modest inflammation triggered by non-injurious dose of LPS. We found that the combined use of Poria and PM in the ratio of 1:2 could significantly ameliorate the PM/LPS-induced liver injury and systemic inflammation. Furthermore, UPLC/QTOF-MS-based metabolomics was performed to identify possible biomarkers and underling biological pathways. Ten metabolites were expressed differentially among LPS, PM/LPS and detoxification-treated groups by PCA and OPLS-DA analysis, which could be potential biomarkers. MetaboAnalyst and pathway enrichment analysis revealed that alterations of these metabolites were primarily involved in three pathways: arginine and proline metabolism, primary bile acid biosynthesis and sphingolipid metabolism. This research provides systematic experimental basis for the hepatoprotective effects of Poria against PM/LPS-induced liver injury for the first time, and these findings may help better understand the mechanisms of underlying pathophysiologic processes.

Background: TAF1B (TATA Box Binding Protein (TBP)-Associated Factor) is an RNA polymerase regulating rDNA activity, stress response, and cell cycle. However, the function of TAF1B in the progression of hepatocellular carcinoma (HCC) is unknown. Objective: In this study, we intended to characterize the crucial role and molecular mechanisms of TAF1B in modulating nucleolar stress in HCC. Methods: We analyzed the differential expression and prognostic value of TAF1B in hepatocellular carcinoma based on The Cancer Genome Atlas (TCGA) database, tumor and paraneoplastic tissue samples from clinical hepatocellular carcinoma patients, and typical hepatocellular carcinoma. We detected cell proliferation and apoptosis by lentiviral knockdown of TAF1B expression levels in HepG2 and SMMC-7721 cells using clone formation, apoptosis, and Western blotting (WB) detection of apoptosis marker proteins. Simultaneously, we investigated the influence of TAF1B knockdown on the function of the preinitiation complex (PIC) by WB, and co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) assays verified the interaction between the complexes and the effect on rDNA activity. Immunofluorescence assays measured the expression of marker proteins of nucleolus stress, fluorescence in situ hybridization (FISH) assays checked the rDNA activity, and qRT-PCR assays tested the pre-rRNA levels. Regarding molecular mechanisms, we investigated the role of p53 and miR-101 in modulating nucleolar stress and apoptosis. Finally, the impact of TAF1B knockdown on tumor growth, apoptosis, and p53 expression was observed in xenograft tumors. Result: We identified that TAF1B was highly expressed in hepatocellular carcinoma and associated with poor prognosis in HCC patients. TAF1B depletion modulated nucleolar stress and apoptosis in hepatocellular carcinoma cells through positive and negative feedback from p53-miR-101. RNA polymerase I transcription repression triggered post-transcriptional activation of miR-101 in a p53-dependent manner. In turn, miR-101 negatively feeds back through direct inhibition of the p53-mediated PARP pathway. Conclusion: These findings broaden our comprehension of the function of TAF1B-mediated nucleolar stress in hepatocellular carcinoma and may offer new biomarkers for exploring prospective therapeutic targets in HCC. [ABSTRACT FROM AUTHOR]

Currently, numerous liver injury cases related to a famous Chinese herb- Polygonum Multiflorum (Heshouwu in Chinese) have attracted great attention in many countries. Our previous work showed that Heshouwu-induced hepatotoxicity belonged to idiosyncratic drug-induced liver injury (IDILI). Unfortunately, the components and mechanisms attributed to IDILI of Heshouwu are difficult to determine and thus remain unknown. Attempts to explore puzzles, we prepared the chloroform (CH)-, ethyl acetate (EA)-, and residue (RE) extracts of Heshouwu to investigate IDILI constituents and underlying mechanisms,using biochemistry, histopathology, and metabolomics examinations. The results showed that co-treatment with non-toxic dose of lipopolysaccharide (LPS) and EA extract could result in evident liver injury, indicated by the significant elevation of plasma alanine aminotransferase and aspartate aminotransferase activities, as well as obvious liver histologic damage; whereas other two separated fractions, CH and RE extracts, failed to induce observable liver injury. Furthermore, 21 potential metabolomic biomarkers that differentially expressed in LPS/EA group compared with other groups without liver injury were identified by untargeted metabolomics, mainly involved two pathways: tricarboxylic acid cycle and sphingolipid metabolism. This work illustrated EA extract had close association with the idiosyncratic hepatotoxicity of Heshouwu and provided a metabolomic insight into IDILI of different extracts from Heshouwu. [ABSTRACT FROM AUTHOR]

The shape transformation characteristics of four-dimensional (4D)-printed bone structures can meet the individual bone regeneration needs, while their structure can be programmed to cross-link or reassemble by stimulating responsive materials. At the same time, it can be used to design vascularized bone structures that help establish a bionic microenvironment, thus influencing cellular behavior and enhancing stem cell differentiation in the postprinting phase. These developments significantly improve conventional three-dimensional (3D)-printed bone structures with enhanced functional adaptability, providing theoretical support to fabricate bone structures to adapt to defective areas dynamically. The printing inks used are stimulus-responsive materials that enable spatiotemporal distribution, maintenance of bioactivity and cellular release for bone, vascular and neural tissue regeneration. This paper discusses the limitations of current bone defect therapies, 4D printing materials used to stimulate bone tissue engineering (e.g., hydrogels), the printing process, the printing classification and their value for clinical applications. We focus on summarizing the technical challenges faced to provide novel therapeutic implications for bone defect repair.

Objective: The aim of this study is to investigate, in ovulatory patients, whether there is a difference in reproductive outcomes following frozen-thawed embryo transfer (FET) in natural cycles (NC) compared to modified natural cycles (mNC).Methods: This retrospective cohort study, performed at the public tertiary fertility clinic, involved all infertile patients undergoing endometrial preparation prior to FET in NC and mNC from January, 2017 to November, 2020. One thousand hundred and sixty-two patients were divided into two groups: mNC group (n = 248) had FET in a NC after ovulation triggering with human chorionic gonadotropin (hCG); NC group (n = 914) had FET in a NC after spontaneous ovulation were observed. The primary outcome was live birth rate. All pregnancy outcomes were analyzed by propensity score matching (PSM) and multivariable logistic regression analyses.Results: The NC group showed a higher live birth rate [344/914 (37.6%) vs. 68/248 (27.4%), P = 0.003; 87/240 (36.3%) vs. 66/240 (27.5%), P = 0.040] than the mNC group before and after PSM analysis. Multivariable analysis also showed mNC to be associated with a decreased likelihood of live birth compared with NC [odds ratio (OR) 95% confidence interval (CI) 0.71 (0.51–0.98), P = 0.039].Conclusion: For women with regular menstrual cycles, NC-FET may have a higher chance of live birth than that in the mNC-FET cycles. As a consequence, it's critical to avoid hCG triggering as much as possible when FETs utilize a natural cycle strategy for endometrial preparation. Nevertheless, further more well-designed randomized clinical trials are still needed to determine this finding.

ObjectiveThe primary objective of the study was to assess traditional Chinese formula DKP supplementation in terms of efficacy and safety on reproductive outcomes of expected poor ovarian responder (POR, POSEIDON Group 4) undergoing in vitro fertilization-embryo transfer (IVF-ET).Design, Setting, and ParticipantsWomen eligible for IVF-ET were invited to participate in this randomized, double-blind, placebo-controlled, superiority trial at academic fertility centers of ten public hospitals in Chinese Mainland. A total of 462 patients (35–44 years) equally divided between DKP and placebo groups with antral follicle count (AFC)