Predictive value of the controlling nutritional status (CONUT) score to assess long-term mortality (10 Years) in patients with hypertension.

BACKGROUND AND AIMS: Malnutrition is associated with poor outcomes in patients with chronic diseases. The aim of this study is to investigate the prevalence of malnutrition in patients with hypertension and relationship between malnutrition severity and long-term mortality in these patients. METHODS AND RESULTS: The study included 11,278 patients with hypertension from the National Health and Nutrition Examination Survey database. The degree of malnutrition was assessed using the Controlled Nutritional Status score, with patients divided into normal, mild, and moderate-to-severe groups. After 10 years of follow-up, the results showed that patients who died had higher CONUT scores, poorer nutritional status, and lower albumin, total cholesterol, and lymphocytes than those who survived (P < 0.05). The Kaplan-Meier analysis revealed that patients with poor nutritional status had a significantly higher risk of all-cause death. In the Non-Lipid Lowering Drugs group, the CONUT score (hazard ratio (HR): 1.225; 95% confidence interval (CI): 1.162-1.292; P < 0.0001), as well as mild (HR: 1.532; 95% CI 1.340-1.751; P < 0.0001) and moderate-to-severe malnutrition (HR: 2.797; 95% CI: 1.441-5.428; P = 0.0024), were independent predictors of long-term mortality. The competing risk regression models showed that cardiovascular and cerebrovascular mortality increased with increasing CONUT scores. The results were robust in both subgroup and sensitivity analyses. CONCLUSIONS: Malnutrition significantly impacts long-term mortality in hypertensive patients. The CONUT score may be a useful tool for assessing the nutritional status of patients with hypertension in the non-lipid-lowering population and for predicting their long-term mortality.

Structurally diverse alkaloids from the Buxus sinica and their cytotoxicity.

Extensive phytochemical study of the methanol extract of twigs and leaves of Buxus sinica resulted in the identification of forty-one Buxus alkaloids, including twenty undescribed ones, namely cyclobuxusinines A-I (1-7, 16 and 20), as well as secobuxusinines A-K (8-15 and 17-19). Their structures were delineated by detailed analysis using various spectroscopic techniques. cyclobuxusinines B (2) was the first Buxus alkaloid, whose CH3-18 was oxidized, implying the presence of special oxidative enzymes in this plant. Secobuxusinines C (10), D (11), and E (12), whose C-12 or C-19 have an OH group substitution, enriched the substituent pattern in Buxus alkaloid and suggested more structurally diverse alkaloids in the Buxus spp. In the assessment of their bioactivities, some of them exhibited significant cytotoxic effects on two human tumor ovarian cancer cell lines. Notably, compound 36 displayed more potent cytotoxic effect against ES2 and A2780 cell lines with the IC50 value of 1.33 µM and 0.48 µM, respectively.

Novel PLCZ1 mutation caused polyspermy during in vitro fertilization.

Failure of oocyte activation, including polyspermy and defects in pronuclear (PN) formation, triggers early embryonic developmental arrest. Many studies have shown that phospholipase C zeta 1 ( PLCZ1 ) mutations cause failure of PN formation following intracytoplasmic sperm injection (ICSI); however, whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization (IVF) remains unknown. Whole-exome sequencing (WES) was performed to identify candidate mutations in couples with primary infertility. Sanger sequencing was used to validate the mutations. Multiple PLCZ1 -mutated sperm were injected into human and mouse oocytes to explore whether PN formation was induced. Assisted oocyte activation (AOA) after ICSI was performed to overcome the failure of oocyte activation. We identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles, including a novel missense mutation c.1154C>T, p.R385Q. PN formation failure was observed during the ICSI cycle. However, injection of multiple PLCZ1- mutated sperm induced PN formation, suggesting that the Ca 2+ oscillations induced by the sperm exceeded the necessary threshold for PN formation. AOA after ICSI enabled normal fertilization, and all patients achieved successful pregnancies. These findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking polyspermy. Furthermore, this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.

Efficacy and safety of tolvaptan in cirrhotic patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Tolvaptan has been approved for the management of cirrhosis-related complications according to the Japanese and Chinese practice guidelines, but not the European or American practice guidelines in view of FDA warning about its hepatotoxicity. This study aimed to systematically evaluate its efficacy and safety in cirrhosis. METHODS: The PubMed, EMBASE, and Cochrane library databases were searched to identify randomized controlled trials (RCTs) evaluating the efficacy and/or safety of tolvaptan in cirrhosis. Risk ratios (RRs) and weight mean differences (WMDs) were calculated. The incidence of common adverse events (AEs) was pooled. RESULTS: Eight RCTs were included. Tolvaptan was significantly associated with higher rates of improvement of ascites (RR = 1.49, P < 0.001) and hyponatremia (RR = 1.80, P = 0.005) and incidence of any AEs (RR = 1.18, P = 0.003), but not serious AEs (RR = 0.86, P = 0.410). Tolvaptan was significantly associated with reductions in body weight (WMD = -1.30 kg, P < 0.001) and abdominal circumference (WMD = -1.71 cm, P < 0.001), and increases in daily urine volume (WMD = 1299.84 mL, P < 0.001) and serum sodium concentration (WMD = 2.57 mmol/L, P < 0.001). The pooled incidences of dry mouth, thirst, constipation, and pollakiuria were 16%, 24%, 6%, and 17%, respectively. CONCLUSION: Short-term use of tolvaptan may be considered in cirrhotic patients with ascites who have inadequate response to conventional diuretics and those with hyponatremia.

[Figure: see text].

Risk of Bleeding in Liver Cirrhosis Receiving Direct Oral Anticoagulants: A Systematic Review and Meta-analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) are effective for the management of thromboembolic disorders. However, bleeding remains a major concern in cirrhotic patients receiving DOACs. METHODS: PubMed, EMBASE, and Cochrane Library databases were searched. The incidence of bleeding episodes in cirrhotic patients receiving DOACs was pooled. Odds ratios (ORs) were calculated to compare the incidence of bleeding episodes in cirrhotic patients who received DOACs versus those who received conventional anticoagulants and did not receive anticoagulants. RESULTS: Twenty-nine studies were included. All bleeding, major bleeding, fatal bleeding, gastrointestinal bleeding, and intracranial hemorrhage episodes were observed in 310/2,469, 100/1,388, 2/611, 166/1,886, and 5/1,147 cirrhotic patients receiving DOACs, respectively. Their pooled incidences were 13, 6, 0, 8, and 0%, respectively. They became higher in subgroup analyses of studies with advanced age, a longer treatment duration, and Child-Turcotte-Pugh class C. Compared with conventional anticoagulants, DOACs were associated with lower incidences of all bleeding (OR = 0.71, 95% confidence interval [CI] = 0.52-0.98) and major bleeding (OR = 0.55, 95% CI = 0.37-0.83) in cirrhotic patients, but not those of fatal bleeding (OR = 0.21, 95% CI = 0.04-1.28), gastrointestinal bleeding (OR = 0.78, 95% CI = 0.52-1.17), or intracranial hemorrhage (OR = 0.36, 95% CI = 0.12-1.12). The incidences of all bleeding (OR = 1.04, 95% CI = 0.22-4.79) and major bleeding (OR = 0.96, 95% CI = 0.26-3.61) did not significantly differ between cirrhotic patients with portal vein thrombosis (PVT) who received DOACs and those who did not receive anticoagulants. CONCLUSION: DOACs carry a low risk of bleeding in liver cirrhosis. Age, treatment duration, and Child-Turcotte-Pugh class may be associated with bleeding in cirrhotic patients receiving DOACs. The risk of bleeding is not increased by DOACs in cirrhotic patients with PVT.

Ni(II)-Mediated Photochemical Oxidative Esterification of Aldehydes with Phenols.

The photopromoted, Ni-catalyzed acceptorless dehydrogenation esterification of phenols and aromatic aldehydes has been achieved in an oxidant- and external photosensitizer-free manner. This reliable and atom-economical transformation was tolerant to a wide range of functional groups and proceeded efficiently to give various aryl benzoates in moderate to high yields. Additionally, this photocatalytic system displayed high activity for the hydrogen-evolution cross coupling of aliphatic aldehydes and phenols employing dual nickel and aromatic aldehyde catalysis.

Synthetic augmentation for semantic segmentation of class imbalanced biomedical images: A data pair generative adversarial network approach.

In recent years, deep learning (DL) has been recognized very useful in the semantic segmentation of biomedical images. Such an application, however, is significantly hindered by the lack of pixel-wise annotations. In this work, we propose a data pair generative adversarial network (DPGAN) for the purpose of synthesizing concurrently the diverse biomedical images and the segmentation labels from random latent vectors. First, a hierarchical structure is constructed consisting of three variational auto-encoder generative adversarial networks (VAEGANs) with an extra discriminator. Subsequently, to alleviate the influence from the imbalance between lesions and non-lesions areas in biomedical segmentation data sets, we divide the DPGAN into three stages, namely, background stage, mask stage and advanced stage, with each stage deploying a VAEGAN. In such a way, a large number of new segmentation data pairs are generated from random latent vectors and then used to augment the original data sets. Finally, to validate the effectiveness of the proposed DPGAN, experiments are carried out on a vestibular schwannoma data set, a kidney tumor data set and a skin cancer data set. The results indicate that, in comparison to other state-of-the-art GAN-based methods, the proposed DPGAN shows better performance in the generative quality, and meanwhile, gains an effective boost on semantic segmentation of class imbalanced biomedical images.

A deep learning model to identify gene expression level using cobinding transcription factor signals.

Gene expression is directly controlled by transcription factors (TFs) in a complex combination manner. It remains a challenging task to systematically infer how the cooperative binding of TFs drives gene activity. Here, we quantitatively analyzed the correlation between TFs and surveyed the TF interaction networks associated with gene expression in GM12878 and K562 cell lines. We identified six TF modules associated with gene expression in each cell line. Furthermore, according to the enrichment characteristics of TFs in these TF modules around a target gene, a convolutional neural network model, called TFCNN, was constructed to identify gene expression level. Results showed that the TFCNN model achieved a good prediction performance for gene expression. The average of the area under receiver operating characteristics curve (AUC) can reach up to 0.975 and 0.976, respectively in GM12878 and K562 cell lines. By comparison, we found that the TFCNN model outperformed the prediction models based on SVM and LDA. This is due to the TFCNN model could better extract the combinatorial interaction among TFs. Further analysis indicated that the abundant binding of regulatory TFs dominates expression of target genes, while the cooperative interaction between TFs has a subtle regulatory effects. And gene expression could be regulated by different TF combinations in a nonlinear way. These results are helpful for deciphering the mechanism of TF combination regulating gene expression.

Effects of Short-Term Human Albumin Infusion for the Prevention and Treatment of Hyponatremia in Patients with Liver Cirrhosis.

Background: Human albumin (HA) infusion is potentially effective for the management of hyponatremia in liver cirrhosis, but the current evidence is very limited. Methods: In this retrospective study, 2414 cirrhotic patients who were consecutively admitted to our hospital between January 2010 and June 2014 were included in the Hospitalization outcome cohort, and 339 cirrhotic patients without malignancy who were consecutively admitted to our department between December 2014 and April 2021 were included in the Long-term outcome cohort. The development and improvement of hyponatremia were compared between patients who received HA infusion during hospitalizations and did not. Logistic and Cox regression analyses were performed to evaluate the association of development and improvement of hyponatremia during hospitalizations with the outcomes. Odds ratios (ORs) and hazard ratios (HRs) were calculated. Results: In the two cohorts, HA infusion significantly decreased the incidence of hyponatremia and increased the rate of improvement of hyponatremia in cirrhotic patients during hospitalizations. In the Hospitalization outcome cohort, the development of hyponatremia during hospitalizations was significantly associated with increased in-hospital mortality (OR = 2.493, p < 0.001), and the improvement of hyponatremia during hospitalizations was significantly associated with decreased in-hospital mortality (OR = 0.599, p = 0.014). In the Long-term outcome cohort, the development of hyponatremia during hospitalizations was significantly associated with decreased long-term survival (HR = 0.400, p < 0.001), and the improvement of hyponatremia during hospitalizations was not significantly associated with long-term survival (HR = 1.085, p = 0.813). Conclusions: HA infusion can effectively prevent the development of hyponatremia and improve hyponatremia in cirrhotic patients during hospitalizations, which may influence the patients' outcomes.

The Expression and Function of Circadian Rhythm Genes in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is among the most common and lethal form of cancer worldwide. However, its diagnosis and treatment are still dissatisfactory, due to limitations in the understanding of its pathogenic mechanism. Therefore, it is important to elucidate the molecular mechanisms and identify novel therapeutic targets for HCC. Circadian rhythm-related genes control a variety of biological processes. These genes play pivotal roles in the initiation and progression of HCC and are potential diagnostic markers and therapeutic targets. This review gives an update on the research progress of circadian rhythms, their effects on the initiation, progression, and prognosis of HCC, in a bid to provide new insights for the research and treatment of HCC.

HIV Tat Protein Induces Myocardial Fibrosis Through TGF-ß1-CTGF Signaling Cascade: A Potential Mechanism of HIV Infection-Related Cardiac Manifestations.

Human immunodeficiency virus (HIV) infection is a risk factor of cardiovascular diseases (CVDs). HIV-infected patients exhibit cardiac dysfunction coupled with cardiac fibrosis. However, the reason why HIV could induce cardiac fibrosis remains largely unexplored. HIV-1 trans-activator of transcription (Tat) protein is a regulatory protein, which plays a critical role in the pathogenesis of various HIV-related complications. In the present study, recombinant Tat was administered to mouse myocardium or neonatal mouse cardiac fibroblasts in different doses. Hematoxylin-eosin and Masson's trichrome staining were performed to observe the histological changes of mice myocardial tissues. EdU staining and MTS assay were used to evaluate the proliferation and viability of neonatal mouse cardiac fibroblasts, respectively. Real-time PCR and western blot analysis were used to detect CTGF, TGF-ß1, and collagen I mRNA and protein expression levels, respectively. The results showed that Tat promoted the occurrence of myocardial fibrosis in mice. Also, we found that Tat increased the proliferative ability and the viability of neonatal mouse cardiac fibroblasts. The protein and mRNA expression levels of TGF-ß1 and CTGF were significantly upregulated both in Tat-treated mouse myocardium and neonatal mouse cardiac fibroblasts. However, co-administration of TGF-ß inhibitor abrogated the enhanced expression of collagen I induced by Tat in neonatal mouse cardiac fibroblasts. In conclusion, Tat contributes to HIV-related cardiac fibrosis through enhanced TGF-ß1-CTGF signaling cascade.

Visible-Light-Induced Nickel-Catalyzed P(O)-C(sp2) Coupling Using Thioxanthen-9-one as a Photoredox Catalysis.

An efficient method has been developed for photocatalytic P(O)-C(sp2) coupling of (hetero)aryl halides with H-phosphine oxides or H-phosphites under the irradiation of visible light or sunlight. The thioxanthen-9-one/nickel dual catalysis mediates this phosphonylation to give arylphosphine oxides and arylphosphonates in moderate to excellent yields. This transformation is widely tolerant to a range of functional groups and proceeds efficiently on a gram scale.

Direct femtosecond laser ablation of large-area TaSe2, SnS2, and TiS2 thick films by a back ablation procedure.

Direct ablation of large-area graphene-like two-dimensional (2D) materials, i.e., tantalum diselenide (TaSe2), stannic disulfide (SnS2), and titanium disulfide (TiS2), by the back ablation method with a femtosecond laser with a repetition rate of 50 MHz and pulse width of 200 fs is studied for the first time to our knowledge. The ablation thresholds of the three kinds of materials are discussed. In addition, the optimization and ablation of narrow grooves on the films are demonstrated. Our work demonstrates the direct femtosecond laser ablation processing of the graphene-like 2D-material films and the potential of 2D-material-film-based devices.

Spark Plasma Diffusion Bonding of TiAl/Ti2AlNb with Ti as Interlayer.

To solve the problem of poor weldability between TiAl-based and Ti2AlNb-based alloys, spark plasma diffusion bonding was employed to join a TiAl alloy and a Ti2AlNb alloy with a pure Ti foil as interlayer at 950 °C/10 KN/60 min. After welding, slow cooling was carried out at a rate of 5 °C/min, followed by homogenization at 800 °C for 24 h. The microstructural evolution and elemental migration of the joint were analyzed via a scanning electron microscope equipped with an energy dispersive spectrometer, while the mechanical properties of the joint were assessed via microhardness and tensile tests. The results show that the spark plasma diffusion bonding formed a joint of TiAl/Ti/Ti2AlNb without microcracks or microvoids, while also effectively protecting the base metal. Before heat treatment, the maximum hardness value (401 HV) appeared at the Ti2AlNb/Ti interface, while the minimum hardness value (281 HV) occurred in the TiAl base metal. The tensile strength of the heat-treated joint at room temperature was measured to be up to 454 MPa, with a brittle fracture occurring in the interlayer. The tensile strength of the joint at 650 °C was measured to be up to 538 MPa, with intergranular cracks occurring in the TiAl base metal.

MiR-135b protects cardiomyocytes from infarction through restraining the NLRP3/caspase-1/IL-1ß pathway.

BACKGROUND: Myocardial infarction (MI) is the most common cause of cardiovascular morbidity and mortality worldwide. Despite the identification of many pathogenic genes associated with MI, the underlying molecular mechanisms remain poorly understood. MicroRNAs (miRNAs, miRs), which regulate target genes at the post-transcriptional level, play a significant role in the regulation of cardiovascular diseases such as MI. Pyroptosis is a caspase-1-dependent pro-inflammatory programmed cell death (PCD) mechanism. The role of pyroptosis in several diseases associated with various miRNAs has been studied extensively. Meanwhile, the role of NOD-like receptor-containing pyrin 3 (NLRP3)/caspase-1/interleukin-1ß (IL-1ß) pathway in cardiac diseases has also been more recognized. METHODS: We established a mice MI model which ligated with the left anterior descending coronary artery and a cardiomyocytes injury model treated by hydrogen peroxide (H2O2) to detect the expressions of miR-135b and NLRP3/caspase-1/IL-1ß pathway. Then miR-135b mimic, agomir-135b, and α-MHC-miR-135b transgenic mice were used to evaluate the effects of miR-135b overexpression. RESULT: We demonstrated that miR-135b was downregulated after cardiomyocytes injury both in vivo and in vitro. Pyroptosis pathway was also activated. MiR-135b overexpression remarkably restored impaired cardiac function and attenuated the upregulation of NLRP3/caspase-1/IL-1ß pathway. CONCLUSIONS: The present findings shed light on the protective role of miR-135b in MI mediated by the inhibition of the NLRP3/caspase-1/IL-1ß pathway.

THz polarization-sensitive characterization of a large-area multilayer rhenium diselenide nanofilm.

Recently, rhenium diselenide (ReSe2) has attracted considerable attention due to its high anisotropy in the layer plane, which makes it a promising candidate for wide applications in electronics and optoelectronics. In this paper, we focus on the polarization-sensitive characteristics of a large-area multilayer ReSe2 nanofilm in the terahertz (THz) region under passive and active conditions by means of THz time-domain spectroscopy. We demonstrate the passive ReSe2 nanofilm with intrinsic THz polarization anisotropy. Maximum transmittance occurs only when the polarization direction of the incident THz wave is along the Re-chains direction. More importantly, THz polarization properties of the active ReSe2 nanofilm by an external electric field applied in a selected directions are also demonstrated. The modulation depth of the THz transmission is up to 16% and the response time is on the order of picoseconds. In addition, a comparative experiment is performed on three kinds of THz polarizers, i.e., ReSe2 nanofilm, carbon nanotubes (CNTs) and wire-gird, respectively. The results prove that the performance of the polarizer based on the active ReSe2 nanofilm is comparable with those of CNTs and the THz wire-gird polarizer. Based on these studies, we believe that the polarization-sensitive ReSe2 nanofilm can find important applications in ultrafast switches, filters and modulation devices in the THz region.

Geographical distribution of the P-R interval reference value of Chinese healthy adults.

To explore the relationship between the geographical factors and P-R interval reference value of healthy adults, and to elucidate the geographical distribution of the P-R interval reference value in Chinese adults, to provide the basis for the standard of P-R interval reference value in different regions. The P-R interval reference value of 64,753 healthy adults in 341 cities (counties) level hospitals, research institutes, and universities in China was collected, and 15 geographical data and P-R interval reference value of healthy people were studied, and then 10 geographical factors with correlation were extracted for further analysis. Using spatial autocorrelation analysis to determine the autocorrelation of data space, using backward regression and ridge regression to construct forecast model, and the optimal prediction model is selected by comparing and evaluating the prediction effect of each model, the spatial distribution map of P-R interval reference value of Chinese healthy adults was constructed by statistical analysis. There was a significant correlation between normal reference value of adult P-R interval reference value and geographical factors. The regression model of normal reference value and geographical factors of adult P-R interval reference value was established by ridge regression analysis method: [Formula: see text] =149.2 + 0.02590X2 + 0.0005000X3 + 0.02634X5-0.05890X6 + 0.0008400X7 + 0.01606X8 + 0.2592X9-0.03638X12 + 5.888X13-0.2126X15 ± 8.6, and ArcGIS10.2. In the software interpolation method, the distribution chart of normal reference value of Chinese adult P-R interval reference value was inserted. Knowing the geographical factors of some places in China, we can use this model to estimate the P-R interval reference value in this region, and to obtain the normal P-R interval reference value between adults anywhere in China.

Pulse dynamics manipulation by the phase bias in a nonlinear fiber amplifying loop mirror.

Pulse dynamics controlling is of great importance for high quality pulse generation in ultra-short pulse fiber lasers. The pulse quality characteristics in terms of pulse duration, energy, chirp profile, tunability, as well as noise feature substantially depend on intracavity pulse propagation dynamics. Here we found that a nonlinear amplifying loop mirror mode-locked thulium-doped fiber laser can switch among enabling operation conventional soliton, stretched-pulse soliton and dissipative soliton regimes only by manipulating an intracavity phase bias device. This provides a simple approach to tailoring ultra-short laser characteristics to different applications.

Generation of 3.9-cycle pulses from the coherent synthesis of two continuous-wave injection seeded optical parametric amplifiers at 53 MHz.

A high repetition-rate, few-cycle light pulse is of great importance due to its potential for a variety of applications, including two-dimensional infrared spectroscopy and time-resolved imaging of molecular structures, which benefit from its ultrabroadband spectrum and ultrashort pulse duration. The generation of an ultrabroadband coherent spectrum is one of the frontiers of ultrafast optics, and accessing such few-cycle pulses is presently under active exploration. Here, we demonstrate a simple yet effective pulse synthesizer. It is based on two continuous-wave (cw) injection-seeded high-repetition-rate optical parametric amplification systems and the following self-phase-modulation dominated spectra-broadening processes. The combined spectrum spans from 1250 to 1670 nm, and a near Fourier-transform-limited 3.9-cycle (19.2 fs) synthesized pulse with a central wavelength of 1470 nm is obtained accordingly.

Femtosecond laser pulse generation with self-similar amplification of picosecond laser pulses.

Compressing picosecond laser pulses to the femtosecond level is an attractive shortcut for obtaining femtosecond laser pulses. However, dechirped pulses generated by nonlinear compression with self-phase modulation (SPM) show obvious pedestals, which are induced by nonlinear chirp accumulation in spectral broadening process and cannot be easily suppressed. Here, we report systematic numerical simulations and experimental studies on self-similar amplification of picosecond pulses in a short gain fiber for obtaining ~100-fs laser pulses with nearly transform-limited (TL) temporal quality. It is demonstrated that self-similar amplification with picosecond seed pulses is only sensitive to pulse duration and pulse energy. Based on this optimization guideline, we built a compact self-similar amplification fiber system with a picosecond fiber laser as the seed source. This system outputs 66-fs pulses with 6.1-W average power at a repetition rate of 30 MHz. Due to the linear chirp produced in self-similar evolution process, compressed pulses show nearly TL temporal quality. It promises an efficient way of obtaining high-quality femtosecond laser pulses from a picosecond laser source.