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Background: Hepatocellular carcinoma (HCC) poses a significant health burden globally, with high mortality rates despite various treatment options. Immunotherapy, particularly immune-checkpoint inhibitors (ICIs), has shown promise, but resistance and metastasis remain major challenges. Understanding the intricacies of the tumor microenvironment (TME) is imperative for optimizing HCC management strategies and enhancing patient prognosis. Methods: This study employed a comprehensive approach integrating multi-omics approaches, including single-cell RNA sequencing (scRNA-seq), bulk RNA sequencing (Bulk RNA-seq), and validation in clinical samples using spatial transcriptomics (ST) and multiplex immunohistochemistry (mIHC). The analysis aimed to identify key factors influencing the immunosuppressive microenvironment associated with HCC metastasis and immunotherapy resistance. Results: HMGB2 is significantly upregulated in HCCTrans, a transitional subgroup associated with aggressive metastasis. Furthermore, HMGB2 expression positively correlates with an immunosuppressive microenvironment, particularly evident in exhausted T cells. Notably, HMGB2 expression correlated positively with immunosuppressive markers and poor prognosis in HCC patients across multiple cohorts. ST combined with mIHC validated the spatial expression patterns of HMGB2 within the TME, providing additional evidence of its role in HCC progression and immune evasion. Conclusion: HMGB2 emerges as a critical player of HCC progression, metastasis, and immunosuppression. Its elevated expression correlates with aggressive tumor behavior and poor patient outcomes, suggesting its potential as both a therapeutic target and a prognostic indicator in HCC management. [ABSTRACT FROM AUTHOR]

Aims: It has been suggested that the triglyceride-glucose (TyG) index is a novel and reliable surrogate marker of insulin resistance (IR). However, its relationship with the risk of end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) remains uncertain. Accordingly, we sought to examine the relationship between the TyG index and ESRD risk in patients with T2DM and CKD. Methods: From January 2013 to December 2021, 1,936 patients with T2DM and CKD hospitalized at Peking University Third Hospital (Beijing, China) were enrolled into the study. The formula for calculating the TyG index was ln [fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. ESRD was defined as an estimated glomerular filtration rate of less than 15 mL/min/1.73 m2 or the commencement of dialysis or renal transplantation. The relationship between the TyG index and ESRD risk was analyzed using Cox proportional hazard regression. Results: 105 (5.42%) participants developed ESRD over a mean follow-up of 41 months. The unadjusted analysis revealed a 1.50-fold (95% confidence interval [CI] 1.17-1.93; P = 0.001) increased risk for ESRD per one unit rise in the TyG index, and the positive association remained stable in the fully adjusted model (hazard ratio, 1.49; 95% CI, 1.12-1.99; P = 0.006). Analysis using restricted cubic spline revealed a significant positive association between the TyG index and ESRD risk. In addition, Kaplan-Meier analysis revealed significant risk stratification with a TyG index cutoff value of 9.5 (P = 0.003). Conclusion: In individuals with T2DM and CKD, a significant and positive association was shown between an elevated TyG index and the risk of ESRD. This conclusion provides evidence for the clinical importance of the TyG index for evaluating renal function decline in individuals with T2DM and CKD. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a predominant contributor to endstage liver disease in the forthcoming decades. Polygonum perfoliatum L. (PPL) is an herbal medicine with anti-lipid peroxidation and anti-inflammatory properties. However, detailed hepatoprotective effects of PPL against NAFLD and its underlying mechanisms are not fully understood. Here, we found that PPL protects against high fat diet (HFD)-induced hepatic steatosis, lipid peroxidation, and glucose-lipid metabolism dysfunction in NAFLD mice. We therefore performed a label-free quantitative proteomic profiling analysis to determine the effect of PPL treatment on liver tissue proteomics and identified that activated PPARs/CPT1A/CPT2-mediated hepatic fatty acid β-oxidation (FAO) process was significantly altered. In vitro treatment of hepatocytes with PPL confirmed this altered process and FAO inhibitor etomoxir (ETO) attenuated the lipid-lowering activity of PPL in hepatocytes. Ultra-high-performance liquid chromatography/Q Exactive-HFX (UPLC/QE-HFX) was used to determine the material basis of anti-NAFLD activity of PPL. Our results have demonstrated the efficacy and potential mechanisms of PPL as an effective pharmacological therapy of NAFLD. [ABSTRACT FROM AUTHOR]

Ferroptosis contributes to the pathogenesis of atrial fibrillation (AF), although the mechanisms are still largely uncovered. The current study was designed to explore the pharmacological effects of icariin against ethanol-induced atrial remodeling, if any, and the mechanisms involved with a focus on SIRT1 signaling. Excessive ethanol-treated animals were administered with Ferrostatin-1, Erastin or icariin to evaluate the potential effects of icariin or ferroptosis. Then, the underling mechanisms was further explored in the in vitro experiments using HL-1 atrial myocytes. Excessive ethanol administration caused significant atrial damage as evidenced by increased susceptibility to AF, altered atrial conduction pattern, atrial enlargement, and enhanced fibrotic markers. These detrimental effects were reversed by Ferrostatin-1 or icariin treatment, while Erastin co-administration markedly abolished the beneficial actions conferred by icariin. Mechanistically, ethanol-treated atria exhibited markedly up-regulated pro-ferroptotic protein (PTGS2, ACSL4, P53) and suppressed anti-ferroptotic molecules (GPX4, FTH1). Icariin treatment inhibited ethanol-induced atrial ferroptosis by reducing atrial mitochondrial damage, ROS accumulation and iron overload. Interestingly, the in vivo and in vitro data showed that icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to AF. Icariin protects against atrial damage by inhibiting ferroptosis via SIRT1 signaling. Its role as a prophylactic/therapeutic drug deserves further clinical study. [ABSTRACT FROM AUTHOR]

Expression of DNA mismatch repair (MMR) protein (MLH1, PMS2, MSH2, and MSH6) in upper tract urothelial carcinoma (UTUC) has been explored in Western cohorts, but it is rarely reported in Eastern cohorts. We aimed to assess the loss of MMR protein expression among Chinese UTUC patients and study its clinicopathological implications. We enrolled 175 UTUC patients at our center and tested the expression of MMR proteins by immunohistochemistry. Then, we explored these patients' clinicopathological characteristics. We found loss of MMR proteins in 19 (10.9%) of 175 patients in our cohort (6 MSH2 and MSH6, 2 MSH6 alone, 6 MSH2 alone, 3 MLH1 and PMS2, and 2 PMS2 alone). Loss of MMR proteins was not a significant prognostic factor of relapse-free survival for these patients. In addition, patients with lower T stage or with bladder cancer history were more likely to have loss of MMR protein expression. At last, two metastatic patients (MSH2 and MSH6 loss; MSH2 loss) with loss of MMR protein experienced tumor recession after several cycles of anti-PD-1 immunotherapy. In conclusion, this is the largest Chinese UTUC cohort study to date that explores the loss of MMR protein expression. The rate of MMR loss observed was comparable to that in the Western UTUC cohort, supporting universal UTUC screening in China. Furthermore, a subset of advanced UTUCs with MMR protein loss are probably immunogenic, for whom single or combined immunotherapy may be potential therapeutic options in the future. [ABSTRACT FROM AUTHOR]

OBJECTIVES To analyze the differential expression of lipid spectrum between ST-segment elevated myocardial infarction (STEMI) and patients with emergency chest pain and excluded coronary artery disease (CAD), and establish the predictive model which could predict STEMI in the early stage. METHODS We conducted a single-center, nested case-control study using the emergency chest pain cohort of Peking University Third Hospital. Untargeted lipidomics were conducted while LASSO regression as well as XGBoost combined with greedy algorithm were used to select lipid molecules. RESULTS Fifty-two STEMI patients along with 52 controls were enrolled. A total of 1925 lipid molecules were detected. There were 93 lipid molecules in the positive ion mode which were differentially expressed between the STEMI and the control group, while in the negative ion mode, there were 73 differentially expressed lipid molecules. In the positive ion mode, the differentially expressed lipid subclasses were mainly diacylglycerol (DG), lysophophatidylcholine (LPC), acylcarnitine (CAR), lysophosphatidyl ethanolamine (LPE), and phosphatidylcholine (PC), while in the negative ion mode, significantly expressed lipid subclasses were mainly free fatty acid (FA), LPE, PC, phosphatidylethanolamine (PE), and phosphatidylinositol (PI). LASSO regression selected 22 lipids while XGBoost combined with greedy algorithm selected 10 lipids. PC (15: 0/18: 2), PI (19: 4), and LPI (20: 3) were the overlapping lipid molecules selected by the two feature screening methods. Logistic model established using the three lipids had excellent performance in discrimination and calibration both in the derivation set (AUC: 0.972) and an internal validation set (AUC: 0.967). In 19 STEMI patients with normal cardiac troponin, 18 patients were correctly diagnosed using lipid model. CONCLUSIONS The differentially expressed lipids were mainly DG, CAR, LPC, LPE, PC, PI, PE, and FA. Using lipid molecules selected by XGBoost combined with greedy algorithm and LASSO regression to establish model could accurately predict STEMI even in the more earlier stage. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the immunophenotype, differential diagnosis, and clinicopathological characteristics of signet‐ring cell carcinoma (SRCC) derived from gastric foveolar epithelium. Methods: Clinical characteristics, endoscopic findings, histopathological features, and follow‐up data of seven cases of SRCC derived from gastric foveolar epithelium with small intramucosal lesions were analyzed. Results: Seven patients with a mean age of 38.3 years were diagnosed with SRCC derived from gastric foveolar epithelium and small intramucosal lesions, all of them were negative for CDH‐1 germline mutation. The glands proliferated and expanded, and then morphologically transformed into signet‐ring cells and formed clonal hyperplastic SRCC, which expanded laterally along the gastric foveolar cells to a length of 3–6 mm. Periodic acid Schiff staining was positive, while CK7 and MUC6 were negative, in all cases. Ki‐67‐positive cells ranged 37%–60%. During a follow‐up period of 6–30 months, no patients experienced tumor recurrence or metastasis. Conclusions: SRCC derived from gastric foveolar epithelium is originated from the proliferative region of the bottom of the gastric pit and gland neck. It is easily missed diagnosed or misdiagnosed as it grows laterally along the gastric foveolar cells. Biological behavior, genetics, and etiology of such SRCC, as well as the clinicopathological characteristics, need to be further studied. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a complex clinical syndrome resulting from the impairment of ventricular filling or ejection of blood or both, leading to considerable morbidity and mortality. Based on left ventricular ejection fraction (LVEF), the 2016 European Society of Cardiology (ESC) guideline firstly classified patients with LVEF in the range of 40% to 49% into heart failure with mid-range ejection fraction. Since then, more and more clinical studies targeting HF with mid-range ejection fraction emerged, indicating that they may benefit from similar therapies to those with LVEF ≤40%. So the latest ESC guideline of HF changed the term 'heart failure with mid-range ejection fraction' to 'heart failure with mildly reduced ejection fraction' (HFmrEF). Simultaneously, burgeoning evidence indicating the emergence of novel technologies (such as speckle tracking echocardiography, cardiac magnetic resonance quantitative imaging), and new biomarkers were conducive to evaluating HF from different perspectives. In this review, we summarized the research progress of HFmrEF in clinical characteristics, prognosis, and treatment, hoping to help cardiologists better evaluate and treat patients of HFmrEF. [ABSTRACT FROM AUTHOR]

With the increase of CO2 greenhouse gas emissions, seeking new energy sources to build a low carbon society has become more urgent since the 21st century. The conversion of CO2 to valuable hydrocarbon fuel driven by solar energy is of great potential and promising to realize the global carbon balance. Exploring semiconductor materials is very important for the photoreduction of CO2. Therefore, it will be the main research direction to fabricate highly efficient photocatalysis materials. This paper reviews recent research on photocatalytic reduction of CO2 to the hydrocarbon fuels in our groups, mainly focusing on nanostructure and component regulations of semiconductor catalysts, including TiO2, V, W, Ge Ga based materials, C3N4 based and some other materials, for the photocatalytic reduction of CO2. [ABSTRACT FROM AUTHOR]

Targeting mitochondrial quality control with melatonin has been found promising for attenuating diabetic cardiomyopathy (DCM), although the underlying mechanisms remain largely undefined. Activation of SIRT6 and melatonin membrane receptors exerts cardioprotective effects while little is known about their roles during DCM. Using high‐fat diet‐streptozotocin‐induced diabetic rat model, we found that prolonged diabetes significantly decreased nocturnal circulatory melatonin and heart melatonin levels, reduced the expressions of cardiac melatonin membrane receptors, and decreased myocardial SIRT6 and AMPK‐PGC‐1α‐AKT signaling. 16 weeks of melatonin treatment inhibited the progression of DCM and the following myocardial ischemia‐reperfusion (MI/R) injury by reducing mitochondrial fission, enhancing mitochondrial biogenesis and mitophagy via re‐activating SIRT6 and AMPK‐PGC‐1α‐AKT signaling. After the induction of diabetes, adeno‐associated virus carrying SIRT6‐specific small hairpin RNA or luzindole was delivered to the animals. We showed that SIRT6 knockdown or antagonizing melatonin receptors abolished the protective effects of melatonin against mitochondrial dysfunction as evidenced by aggravated mitochondrial fission and reduced mitochondrial biogenesis and mitophagy. Additionally, SIRT6 shRNA or luzindole inhibited melatonin‐induced AMPK‐PGC‐1α‐AKT activation as well as its cardioprotective actions. Collectively, we demonstrated that long‐term melatonin treatment attenuated the progression of DCM and reduced myocardial vulnerability to MI/R injury through preserving mitochondrial quality control. Melatonin membrane receptor‐mediated SIRT6‐AMPK‐PGC‐1α‐AKT axis played a key role in this process. Targeting SIRT6 with melatonin treatment may be a promising strategy for attenuating DCM and reducing myocardial vulnerability to ischemia‐reperfusion injury in diabetic patients. [ABSTRACT FROM AUTHOR]

Vapour equilibrium technique (VET) is usually used to determine the water retention curve of soils. It is a suction-controlled technique where the soil specimen is allowed to reach the suction equilibrium in a desiccator where the relative humidity is controlled by a chemical solution. The suction equilibrium condition is deemed to have been reached when its soil moisture content does not change with time. Therefore, VET requires continuous monitoring for moisture content of the testing soil without disturbing the water vapour exchange process. The aim of this study is to present the electrical resistivity (ER) method that can be used to measure the moisture content of the specimen in VET without disturbance. The ER method is able to monitor the changes of soil moisture with time, and to successfully determine the time at which the soil moisture reaches the equilibrium state. The total suction equilibrium condition was validated independently with the suction measurements using a WP4C water potential meter. The results show good agreement between the total suction equilibrium condition determined by the proposed ER method and the WP4C measurements. [ABSTRACT FROM AUTHOR]

Haishengsu (HSS) is an active natural extract isolated from Tegillarca granosa, which has previously been demonstrated to inhibit the proliferation of several types of cancer cells in vitro. Our previous study indicated that HSS may induce apoptosis to suppress growth of human hepatocellular carcinoma BEL‑7402 cells by activating Fas pathway. The present study demonstrated that HSS treatment induces the in vitro apoptosis of BEL‑7402 cells via the mitochondrial‑mediated apoptotic pathway detected by DNA fragmentation assay, caspase activity assay and transmission electron microscopy assay, and inhibits tumor xenograft growth in vivo. Alterations in apoptotic regulatory proteins were detected, including decreased expression of B‑cell lymphoma2 (Bcl‑2), upregulation of Bcl‑2‑associated X protein and mitochondrial cytochrome c release, and downstream activation of apoptotic signaling. Furthermore, apoptotic induction was caspase‑dependent, as indicated by cleavage of the caspase substrate, poly (ADP‑ribose) polymerase. Oral administration of 62.5‑250 mg/kg HSS markedly educed the growth of hepatocellular carcinoma tumor xenografts in nude mice. In addition, immunohistochemical staining for caspase‑3 protein and transmission electron microscopy further indicated the induction of apoptosis in these tumor tissues. Taken together, the present study demonstrated that HSS may effectively induce apoptosis to suppress the growth of BEL‑7402 cells in vitro and in vivo, and therefore may hold promise for further development as a novel cancer therapy. [ABSTRACT FROM AUTHOR]

Objective Biocompatible polymer everolimus-eluting stents (EES) are associated with risk of stent thrombosis (ST); biodegradable polymer drugeluting stents (BP-DES) were designed to reduce these risks. However, the long-term benefits are not completely clear. Method We undertook a meta-analysis of randomized studies identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database. Primary outcome was the risk of ST. Results Twelve studies (11,692 patients) were included. Overall, compared with EES, BP-DES were associated with a broadly equivalent risk of defi- nite and probable ST (OR, 0.91; 95% CI, 0.55 to 1.50; P = 0.71; I² = 0.0%), early ST (OR, 2.25; 95% CI, 0.78 to 6.47; P = 0.13; I² = 0.0%), late ST (OR, 3.57; 95% CI, 0.42 to 30.58; P = 0.25; I² = 0.0%) and very late ST (OR, 0.50; 95% CI, 0.05 to 5.52; P = 0.57). Meanwhile, there was no significant difference in all-cause mortality (OR, 1.07; 95% CI, 0.86 to 1.32; P = 0.54; I² = 0.0%), myocardial infarction (OR, 1.07; 95% CI, 0.88 to 1.30; P = 0.47; I² = 0.0%), target vessel revascularization (OR, 1.02; 95% CI, 0.86 to 1.21; P = 0.80; I² = 12.0%), and major adverse cardiac events (OR, 1.04; 95% CI, 0.93 to 1.16; P = 0.53; I² = 0.0%). Furthermore, angiographic data showed that in-stent and in-segment late luminal loss were similar between the two groups. Conclusions Compared with biocompatible polymer EES, biodegradable polymer stents appear to have equivalent clinical benefits. [ABSTRACT FROM AUTHOR]

In order to run CFD codes more efficiently on large scales, the parallel computing has to be employed. For example, in industrial scales, it usually uses tens of thousands of mesh cells to capture the details of complex geometries. How to distribute thesemesh cells among the multiprocessors for obtaining a good parallel computing performance (HPC) is really a challenge. Due to dealing with the massive mesh cells, it is difficult for the CFD codes without parallel optimizations to handle this kind of large-scale computing. Some of the open source mesh partitioning software packages, such as Metis, ParMetis, Scotch, PT-Scotch, and Zoltan, are able to deal with the distribution of large number of mesh cells. Therefore they were employed as the parallel optimization tools ported into Code Saturne, an open source CFD code, for testing if they can solve the issue of dealing with massive mesh cells for CFD codes. Through the studies, it was found that the mesh partitioning optimization software packages can help CFD codes not only deal with massive mesh cells but also have a good HPC. [ABSTRACT FROM AUTHOR]

To observe the effects of Tongguan Capsule (通冠胶囊, TGC) on post-myocardial infarction ventricular remodeling and heart function in rats. A rat model of acute myocardial infarction (AMI) was established by coronary ligation. Experimental rats were randomized to 4 groups including three model groups (Group A: captopril 5 mg/kg · day, n=7; Group B: TGC 10 g/kg · day, n=7; and Group C: placebo, n=8), and a sham-control group (Group D: blank control, n=6). Animals were treated for 4 weeks. The cardiac function of rats was assessed at the end of the experiment based on left ventricular ejection fraction (LVEF) and left ventricular short axis fractional shortening (LVFS) detected by colored echocardiography; meanwhile, the condition of ventricular remodeling was observed through the levels of left ventricular mass (LVM), plasma aldosterone (ALD), myocardial angiotensin II (Ang II) and myocardial collagen measurements. At the end of the experiment, LVEF and LVFS in Group A and B were improved significantly, while those in Group C were unchanged, the LVEF in Group A, B, C, and D was 0.57±0.46, 0.61±0.08, 0.36±0.55 and 0.76±0.02, respectively; and their LVFS was 0.31±0.52, 0.34±0.04, 0.23±0.57 and 0.45±0.03, respectively. The difference was statistically significant when comparing the two indexes in Group A and B with those in Group C and D ( P<0.05). LVM, levels of plasma ALD and myocardial Ang II were lower in Group A and B than in Group C, but a comparison between Group A and B showed an insignificant difference in lowering LVM and ALD, while the lowering of Ang II was more significant in Group B than in Group A (754.7 ± 18.7 pg/mL vs 952.6±17.6 pg/mL, P<0.05). Morphological examination showed that in Group A and B the swollen myocardial cells had shrunk, with regularly arranged myocardial fibers and decreased collagen proliferation, but the improvements in Group B were more significant. TGC could markedly improve the post-infarction ventricular remodeling and cardiac function in rats, showing that the efficacy was better than or equal to that of captopril. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical efficacy of Qianlie'an (QLA) suppository via anal route administration in treating chronic prostatitis syndrome. Methods: A randomized open-labelled prospective controlled trial was carried out. The total of 120 patients with chronic prostatitis syndrome were randomly divided into 2 groups: 60 patients in the treated group who were treated with QLA suppository combined with ofloxacin, and the other 60 patients in the control group who were given ofloxacin alone. The efficacy was evaluated by WBC count in the expressed prostatic secretion (EPS) and the Chronic Prostatitis Symptom Index (CPSI) made by the National Institute of Health (NIH). The clinical effects were also observed in a 4-week follow-up. Results: All but six cases completed the trial and the follow-up. It showed that in the treated group recovery rate was 17. 2%, markedly effective rate 34. 5%, effective rate 32. 8%, total markedly effective rate 51. 7%, and total effective rate 84. 5%, all of which were superior to those in the control group (total markedly effective rate 32.1% and total effective rate 66.1%, respectively), P < 0.01. Conclusion: Administration of QLA suppository via anal route combined with oral antibiotics is an effective therapy for chronic prostatitis syndrome. It can relieve the symptoms of chronic prostatitis syndrome markedly and rapidly. It is a new choice for treatment of the disease. [ABSTRACT FROM AUTHOR]

We have fabricated and characterized GaN-based vertical cavity surface emitting lasers (VCSELs) with a unique active region structure, in which three sets of InGaN asymmetric coupled quantum wells are placed in a half-wavelength (0.5λ) length. Lasing action was achieved under optical pumping at room temperature with a threshold pumping energy density of about 6.5 mJ/cm2. The laser emitted a blue light at 449.5 nm with a narrow linewidth below 0.1 nm and had a high spontaneous emission factor of about 3.0×10-2. The results indicate that this active region structure is useful in reducing the process difficulties and improving the threshold characteristics of GaN-based VCSELs. [ABSTRACT FROM AUTHOR]