Metabolic reprogramming in hepatocellular carcinoma: a bibliometric and visualized study from 2011 to 2023.

Background and aims: Metabolic reprogramming has been found to be a typical feature of tumors. Hepatocellular carcinoma (HCC), a cancer with high morbidity and mortality, has been extensively studied for its metabolic reprogramming-related mechanisms. Our study aims to identify the hotspots and frontiers of metabolic reprogramming research in HCC and to provide guidance for future scientific research and decision-making in HCC metabolism. Methods: Relevant studies on the metabolic reprogramming of HCC were derived from the Web of Science Core Collection (WoSCC) database up until November 2023. The bibliometrix tools in R were used for scientometric analysis and visualization. Results: From 2011 to 2023, a total of 575 publications were obtained from WoSCC that met the established criteria. These publications involved 3,904 researchers and 948 organizations in 37 countries, with an average annual growth rate of 39.11% in research. These studies were published in 233 journals, with Cancers (n = 29) ranking first, followed by Frontiers in Oncology (n = 20) and International Journal of Molecular Sciences (n = 19). The top ten journals accounted for 26% of the 575 studies. The most prolific authors were Wang J (n = 14), Li Y (n = 12), and Liu J (n = 12). The country with the most publications is China, followed by the United States, Italy, and France. Fudan University had the largest percentage of research results with 15.48% (n = 89). Ally A's paper in Cell has the most citations. A total of 1,204 keywords were analyzed, with the trend themes such as "glycolysis," "tumor microenvironment," "Warburg effect," "mitochondria," "hypoxia ," etc. Co-occurrence network and cluster analysis revealed the relationships between keywords, authors, publications, and journals. Moreover, the close collaboration between countries in this field was elucidated. Conclusion: This bibliometric and visual analysis delves into studies related to metabolic reprogramming in HCC between 2012 and 2023, elucidating the characteristics of research in this field, which has gradually moved away from single glycolipid metabolism studies to the integration of overall metabolism in the body, pointing out the trend of research topics, and the dynamics of the interaction between the tumor microenvironment and metabolic reprogramming will be the future direction of research, which provides blueprints and inspirations for HCC prevention and treatment programs to the researchers in this field.Systematic Review Registration: [https://www.bibliometrix.org].

Rapid and extensive SARS-CoV-2 Omicron variant infection wave revealed by wastewater surveillance in Shenzhen following the lifting of a strict COVID-19 strategy.

Wastewater-based epidemiology (WBE) has emerged as a promising tool for monitoring the spread of COVID-19, as SARS-CoV-2 can be shed in the faeces of infected individuals, even in the absence of symptoms. This study aimed to optimize a prediction model for estimating COVID-19 infection rates based on SARS-CoV-2 RNA concentrations in wastewater, and reveal the infection trends and variant diversification in Shenzhen, China following the lifting of a strict COVID-19 strategy. Faecal samples (n = 4337) from 1204 SARS-CoV-2 infected individuals hospitalized in a designated hospital were analysed to obtain Omicron variant-specific faecal shedding dynamics. Wastewater samples from 6 wastewater treatment plants (WWTPs) and 9 pump stations, covering 3.55 million people, were monitored for SARS-CoV-2 RNA concentrations and variant abundance. We found that the viral load in wastewater increased rapidly in December 2022 in the two districts, demonstrating a sharp peak in COVID-19 infections in late-December 2022, mainly caused by Omicron subvariants BA.5.2.48 and BF.7.14. The prediction model, based on the mass balance between total viral load in wastewater and individual faecal viral shedding, revealed a surge in the cumulative infection rate from <0.1 % to over 70 % within three weeks after the strict COVID-19 strategy was lifted. Additionally, 39 cryptic SARS-CoV-2 variants were identified in wastewater, in addition to those detected through clinical surveillance. These findings demonstrate the effectiveness of WBE in providing comprehensive and efficient assessments of COVID-19 infection rates and identifying cryptic variants, highlighting its potential for monitoring emerging pathogens with faecal shedding.

Icariin promotes cell adhesion for osteogenesis in bone marrow stromal cells via binding to integrin α5ß1.

BACKGROUND AND PURPOSE: Icariin, an 8-prenylated flavonoid glycoside, is an anabolic agent that could exert rapid estrogenic actions via ligand-independent activation of estrogen receptor alpha (ERα) in osteoblastic cells to promote osteogenesis. However, relatively little is known about its direct cellular target, its protective effects, and cell adhesion activities in bone marrow stromal cells (BMSCs) against microgravity. In the present study, the effects of icariin on osteogenesis and cell adhesion under microgravity were examined with the involvement of integrin receptor α5ß1, connexin 43, and CAMs. STUDY DESIGN AND METHODS: Icariin was orally administered to 6-month-old ovariectomized (OVX) Sprague-Dawley (SD) rats for 3 months through daily intake of phytoestrogen-free rodent diets containing icariin at 2 different dosages (50 and 500 ppm). BMSCs were harvested for experiments and RNA-sequencing analysis to examine the mechanism of action of icariin and its direct cellular target in stimulating osteogenesis. RESULTS: The results revealed that icariin induced the expression of cell adhesion molecules (CAMs) and protected against microgravity-induced disruption of actin cytoskeleton and the loss of osteogenic activities in BMSCs through the activation of connexin-43 (Cx43) and Ras homolog family member A (RhoA) and Rac family small GTPase 1 (Rac1)-mediated signaling pathways. Computerized molecular docking techniques and the competitive solid-phase binding ELISA assay confirmed that icariin could be a direct ligand of integrin alpha 5 beta 1 (α5ß1), and it could also increase the protein expression of integrin α5ß1 for mechanosensing. CONCLUSION: Our findings suggest that icariin could directly activate cell adhesion signaling by binding to integrin α5ß1, which opens up new avenues for the development of integrin α5ß1 ligand as an agent to protect against unloading-induced bone loss.

Pt nanoshells with a high NIR-II photothermal conversion efficiency mediates multimodal neuromodulation against ventricular arrhythmias.

Autonomic nervous system disorders play a pivotal role in the pathophysiology of cardiovascular diseases. Regulating it is essential for preventing and treating acute ventricular arrhythmias (VAs). Photothermal neuromodulation is a nonimplanted technique, but the response temperature ranges of transient receptor potential vanilloid 1 (TRPV1) and TWIK-related K+ Channel 1 (TREK1) exhibit differences while being closely aligned, and the acute nature of VAs require that it must be rapid and precise. However, the low photothermal conversion efficiency (PCE) still poses limitations in achieving rapid and precise treatment. Here, we achieve a nearly perfect blackbody absorption and a high PCE in the second near infrared (NIR-II) window (73.7% at 1064 nm) via a Pt nanoparticle shell (PtNP-shell). By precisely manipulating the photothermal effect, we successfully achieve rapid and precise multimodal neuromodulation encompassing neural activation (41.0-42.9 °C) and inhibition (45.0-46.9 °C) in a male canine model. The NIR-II photothermal modulation additionally achieves multimodal reversible autonomic modulation and confers protection against acute VAs associated with myocardial ischemia and reperfusion injury in interventional therapy.

Potential application of aptamers combined with DNA nanoflowers in neurodegenerative diseases.

The efficacy of neurotherapeutic drugs hinges on their ability to traverse the blood-brain barrier and access the brain, which is crucial for treating or alleviating neurodegenerative diseases (NDs). Given the absence of definitive cures for NDs, early diagnosis and intervention become paramount in impeding disease progression. However, conventional therapeutic drugs and existing diagnostic approaches must meet clinical demands. Consequently, there is a pressing need to advance drug delivery systems and early diagnostic methods tailored for NDs. Certain aptamers endowed with specific functionalities find widespread utility in the targeted therapy and diagnosis of NDs. DNA nanoflowers (DNFs), distinctive flower-shaped DNA nanomaterials, are intricately self-assembled through rolling ring amplification (RCA) of circular DNA templates. Notably, imbuing DNFs with diverse functionalities becomes seamlessly achievable by integrating aptamer sequences with specific functions into RCA templates, resulting in a novel nanomaterial, aptamer-bound DNFs (ADNFs) that amalgamates the advantageous features of both components. This article delves into the characteristics and applications of aptamers and DNFs, exploring the potential or application of ADNFs in drug-targeted delivery, direct treatment, early diagnosis, etc. The objective is to offer prospective ideas for the clinical treatment or diagnosis of NDs, thereby contributing to the ongoing efforts in this critical field.

Gastrodin Improves the Activity of the Ubiquitin-Proteasome System and the Autophagy-Lysosome Pathway to Degrade Mutant Huntingtin.

Gastrodin (GAS) is the main chemical component of the traditional Chinese herb Gastrodia elata (called "Tianma" in Chinese), which has been used to treat neurological conditions, including headaches, epilepsy, stroke, and memory loss. To our knowledge, it is unclear whether GAS has a therapeutic effect on Huntington's disease (HD). In the present study, we evaluated the effect of GAS on the degradation of mutant huntingtin protein (mHtt) by using PC12 cells transfected with N-terminal mHtt Q74. We found that 0.1-100 µM GAS had no effect on the survival rate of Q23 and Q74 PC12 cells after 24-48 h of incubation. The ubiquitin-proteasome system (UPS) is the main system that clears misfolded proteins in eukaryotic cells. Mutated Htt significantly upregulated total ubiquitinated protein (Ub) expression, decreased chymotrypsin-like, trypsin-like and caspase-like peptidase activity, and reduced the colocalization of the 20S proteasome with mHtt. GAS (25 µM) attenuated all of the abovementioned pathological changes, and the regulatory effect of GAS on mHtt was found to be abolished by MG132, a proteasome inhibitor. The autophagy-lysosome pathway (ALP) is another system for misfolded protein degradation. Although GAS downregulated the expression of autophagy markers (LC3II and P62), it increased the colocalization of LC3II with lysosomal associated membrane protein 1 (LAMP1), which indicates that ALP was activated. Moreover, GAS prevented mHtt-induced neuronal damage in PC12 cells. GAS has a selective effect on mHtt in Q74 PC12 cells and has no effect on Q23 and proteins encoded by other genes containing long CAGs, such as Rbm33 (10 CAG repeats) and Hcn1 (>30 CAG repeats). Furthermore, oral administration of 100 mg/kg GAS increased grip strength and attenuated mHtt aggregates in B6-hHTT130-N transgenic mice. This is a high dose (100 mg/kg GAS) when compared with experiments on HD mice with other small molecules. We will design more doses to evaluate the dose-response relationship of the inhibition effect of GAS on mHtt in our next study. In summary, GAS can promote the degradation of mHtt by activating the UPS and ALP, making it a potential therapeutic agent for HD.

Role of S100ß in Unstable Angina Pectoris: Insights from Quantitative Flow Ratio.

BACKGROUND AND OBJECTIVE: Disturbed autonomic nervous system (ANS) may promote inflammatory, immune, and oxidative stress responses, which may increase the risk of acute coronary events. S100ß has been proposed as a biomarker of neuronal injury that would provide an insightful understanding of the crosstalk between the ANS, immune-inflammatory cells, and plaques that drive atherosclerosis. This study investigates the correlation between S100ß, and functional coronary stenosis as determined by quantitative flow ratio (QFR). METHODS: Patients with unstable angina pectoris (UAP) scheduled for coronary angiography and QFR were retrospectively enrolled. Serum S100ß levels were determined by enzyme-linked immunosorbent assay. The Gensini score was used to estimate the extent of atherosclerotic lesions and the cumulative sum of three-vessel QFR (3V-QFR) was calculated to estimate the total atherosclerotic burden. RESULTS: Two hundred thirty-three patients were included in this study. Receiver operator characteristic (ROC) curve indicated that S100ß>33.28 pg/mL predicted functional ischemia in patients with UAP. Multivariate logistic analyses showed that a higher level of S100ß was independently correlated with a functional ischemia-driven target vessel (QFR ≤0.8). This was also closely correlated with the severity of coronary lesions, as measured by the Gensini score (OR = 5.058, 95% CI: 2.912-8.793, p <0.001). According to 3V-QFR, S100ß is inversely associated with total atherosclerosis burden (B = -0.002, p <0.001). CONCLUSIONS: S100ß was elevated in the functional ischemia stages of UAP. It was independently associated with coronary lesion severity as assessed by Gensini score and total atherosclerosis burden as estimated by 3V-QFR in patients with UAP.

Development of an FAP-Targeted PET Probe Based on a Novel Quinolinium Molecular Scaffold.

Fibroblast activation protein (FAP) has recently gained significant attention as a promising tumor biomarker for both diagnosis and therapeutic applications. A series of radiopharmaceuticals based on fibroblast activation protein inhibitors (FAPIs) have been developed and translated into the clinic. Though some of them such as radiolabeled FAPI-04 probes have achieved favorable in vivo imaging performance, further improvement is still highly desired for obtaining radiopharmaceuticals with a high theranostics potential. In this study, we innovatively designed an FAPI ligand SMIC-3002 by changing the core quinoline motif of FAPI-04 to the quinolinium scaffold. The engineered molecule was further radiolabeled with 68Ga to generate a positron emission tomography (PET) probe, [68Ga]Ga-SMIC-3002, which was then evaluated in vitro and in vivo. [68Ga]Ga-SMIC-3002 demonstrated high in vitro stability, nanomolar affinity for FAP (8 nM for protein, 23 nM for U87MG cells), and specific uptake in FAP-expressing tumors, with a tumor/muscle ratio of 19.1 and a tumor uptake of 1.48 ± 0.03 ID/g% at 0.5 h in U87MG tumor-bearing mice. In summary, the quinolinium scaffold can be successfully used for the development of the FAP-targeted tracer. [68Ga]Ga-SMIC-3002 not only shows high potential for clinical translation but also offers insights into designing a new generation of FAPI tracers.

Acupuncture in Traditional Chinese Medicine: A Complementary Approach for Cardiovascular Health.

Cardiovascular diseases (CVDs) are increasingly prevalent in clinical settings. With the continuous improvement of people's living standards, the gradual acceleration of the pace of life, and the deterioration of the living environment in recent years, the incidence of CVDs is increasing annually. The prevalence of CVDs among individuals aged 50 and above is notably elevated, posing a significant risk to patients' well-being and lives. At this juncture, numerous clinical treatment choices are available for managing CVDs, with traditional Chinese medicine (TCM) therapy standing out as a practical, safe, and reliable option. Over the recent years, there has been growing acknowledgement among both medical professionals and patients. With the expanding integration of TCM in the treatment of various clinical conditions, the use of TCM in managing CVDs has gained significant attention within the medical community, potentially emerging as an efficacious approach for addressing cardiovascular diseases. This article conducts a comprehensive review of the TCM approach, particularly acupuncture, as a supplementary treatment for CVDs, highlighting its ability to effectively lower blood pressure, decrease coronary artery events, mitigate arrhythmias, and enhance cardiac function when used alongside conventional medication. The review underscores the promise of acupuncture in enhancing cardiovascular health, although variations in research methodologies necessitate standardized applications.

Blockade of mesenteric and omental adipose tissue sensory neurons improves cardiac remodeling through sympathetic pathway.

Mesenteric and omental adipose tissue (MOAT) communicates directly with the heart through the secretion of bioactive molecules and indirectly through afferent signaling to the central nervous system. Myocardial infarction (MI) may induce pathological alterations in MOAT, which further affects cardiac function. Our study revealed that MI induced significant MOAT transcriptional changes in genes related with signal transduction, including adiponectin (APN), neuropeptide Y (NPY), and complement C3 (C3), potentially influencing afferent activity. We further found that MOAT sensory nerve denervation with capsaicin (CAP) prevented cardiac remodeling, improved cardiac function, and reversed cardiac sympathetic nerve hyperactivation in the MI group, accompanied by reduced serum norepinephrine. In addition, CAP reversed the elevated MOAT afferent input and brain-heart sympathetic outflow post-MI, increasing APN and NPY and decreasing C3 and serum proinflammatory factors. These results demonstrated that blockade of the MOAT afferent sensory nerve exerts a cardioprotective effect by inhibiting the brain-heart sympathetic axis.

The viral trends and genotype diversity of norovirus in the wastewater of Shenzhen, China.

Norovirus (NoV) is the primary cause of acute gastroenteritis (AGE) on a global scale. Numerous studies have demonstrated the immense potential of wastewater surveillance in monitoring the prevalence and spread of NoV within communities. This study employed a one-step reverse transcription-quantitative PCR to quantify NoV GI/GII in wastewater samples (n = 2574), which were collected once or twice a week from 38 wastewater treatment plants from March 2023 to February 2024 in Shenzhen. The concentrations of NoV GI and GII ranged from 5.0 × 104 to 1.7 × 106 copies/L and 4.1 × 105 to 4.5 × 106 copies/L, respectively. The concentrations of NoV GII were higher than those of NoV GI. Spearman's correlation analysis revealed a moderate correlation between the concentration of NoV in wastewater and the detection rates of NoV infections in sentinel hospitals. Baseline values were established for NoV concentrations in Shenzhen's wastewater, providing a crucial reference point for implementing early warning systems and nonpharmaceutical interventions to mitigate the impact of potential outbreaks. A total of 24 NoV genotypes were identified in 100 wastewater samples by sequencing. Nine genotypes of NoV GI were detected, with the major genotypes being GI.4 (38.6 %) and GI.3 (21.8 %); Fifteen genotypes of NoV GII were identified, with GII.4 (53.6 %) and GII.17 (26.0 %) being dominant. The trends in the relative abundance of NoV GI/GII were significantly different, and the trends in the relative abundance of NoV GII.4 over time were similar across all districts, suggesting a potential risk of cross-regional spread. Our findings underscore the effectiveness of wastewater surveillance in reflecting population-level NoV infections, capturing the diverse array of NoV genotypes, and utilizing NoV RNA in wastewater as a specific indicator to supplement clinical surveillance data, ultimately enhancing our ability to predict the timing and intensity of NoV epidemics.

A GABAergic system in atrioventricular node pacemaker cells controls electrical conduction between the atria and ventricles.

Physiologically, the atria contract first, followed by the ventricles, which is the prerequisite for normal blood circulation. The above phenomenon of atrioventricular sequential contraction results from the characteristically slow conduction of electrical excitation of the atrioventricular node (AVN) between the atria and the ventricles. However, it is not clear what controls the conduction of electrical excitation within AVNs. Here, we find that AVN pacemaker cells (AVNPCs) possess an intact intrinsic GABAergic system, which plays a key role in electrical conduction from the atria to the ventricles. First, along with the discovery of abundant GABA-containing vesicles under the surface membranes of AVNPCs, key elements of the GABAergic system, including GABA metabolic enzymes, GABA receptors, and GABA transporters, were identified in AVNPCs. Second, GABA synchronously elicited GABA-gated currents in AVNPCs, which significantly weakened the excitability of AVNPCs. Third, the key molecular elements of the GABAergic system markedly modulated the conductivity of electrical excitation in the AVN. Fourth, GABAA receptor deficiency in AVNPCs accelerated atrioventricular conduction, which impaired the AVN's protective potential against rapid ventricular frequency responses, increased susceptibility to lethal ventricular arrhythmias, and decreased the cardiac contractile function. Finally, interventions targeting the GABAergic system effectively prevented the occurrence and development of atrioventricular block. In summary, the endogenous GABAergic system in AVNPCs determines the slow conduction of electrical excitation within AVNs, thereby ensuring sequential atrioventricular contraction. The endogenous GABAergic system shows promise as a novel intervention target for cardiac arrhythmias.

Synthesis and biological evaluation of multimodal monoaminergic arylpiperazine derivatives with potential antidepressant profile.

Depression is a common psychiatric disorder with an estimated global prevalence of 4.4 %. Here, we designed a series of new multimodal monoaminergic arylpiperazine derivatives using a pharmacophore hybrid approach and synthesized them for the treatment of depression. Molecular docking was employed to elucidate the differences in activity and selectivity of the corresponding compounds on SERT, NET, and DAT. In vitro experiments demonstrated that compound A3 has a relatively balanced multi-target activity profile with SERT reuptake inhibition (IC50 = 12 nM), NET reuptake inhibition (IC50 = 78 nM), DAT reuptake inhibition (IC50 = 135 nM), and 5-HT1AR agonism (EC50 = 34 nM). Pharmacokinetic experiments revealed that A3 exhibited excellent bioavailability and low clearance in mice. Subsequent behavioral experiments further confirmed its significant antidepressant effects. These results further highlight the rationality of our design strategy.

Incoherent partial superposition modeling for single-shot angle-resolved ellipsometry measurement of thin films on transparent substrates.

Ellipsometric measurement of transparent samples suffers from substrate backside reflection challenges, including incoherent and partial superposition issues. The recently developed angle-resolved ellipsometry (ARE) can naturally eliminate the backside reflections of substrates with a micro-spot equivalent thickness or thicker; however, for thinner substrates, ARE working with general incoherent backside reflection models shows significant inaccuracy or measurement failure. In this paper, an incoherent partial superposition (IPS) model is proposed to characterize the optical superposition effect between the frontside and uncertain backside reflections from an unknown substrate. IPS introduces a cosine-like correction of the backside reflection, corresponding to the overlapping-area change of backside and frontside reflections along with incident angles. Benefiting from ARE's wide-angle spectral imaging capability, IPS achieves single-shot measurement of thin film thicknesses on transparent substrates of unknown thickness. An ARE system was built and calibrated regarding the linear relationship between the cosine-corrected angular frequencies and substrate thicknesses. Then, commercial ITO films on glasses of different thicknesses ranging from 200 to 1000 µm were measured. Experimental results show that IPS-ARE results in a root-mean-square accuracy error of ∼1 nm in film thickness measurement and provides a ∼77% error reduction from general incoherent backside reflection models.

Numerical simulation and theoretical study on the impact of wind-sand flow of high-speed trains in long tunnel space.

When high-speed trains (HST) run in enclosed spaces such as long tunnels, the thermal accumulation of their suspension devices is continuous and cannot be effectively dissipated. In addition, previous experiments or simulations for the heat dissipation of HST in tunnel spaces did not consider the impact of sand. To clarify the impact of HWS-LT on the heat accumulation of HST equipment cabin, this study used the CFD method to numerically simulate the impact of different wind-sand flow concentrations or no-sand wind on the cooling of equipment in the long tunnel space. Firstly, the sand particles in the wind-sand flow gather at the tunnel entrance and enter the equipment cabin with the train as it enters the tunnel. This boundary condition is more in line with actual engineering situations. Secondly, both flows show asymmetric intrusion into the cabin due to the asymmetrical tunnel arrangement, but the sand particles in the wind-sand flow are affected by the vortices and tunnel walls, resulting in more asymmetric flow and some particles being trapped in the grids or filters, leading to outflow ρQ < inflow ρQ. Under the wind-sand flow condition, the temperature of some equipment surfaces shows more significant increases than under the no-sand wind. Finally, contrary to popular perception, the wind-sand flow carrying sand particles can dissipate heat more effectively than no-sand wind, and the higher the volume fraction φ within a certain concentration range, the better the heat dissipation effect. This is because the wind-sand flow has a higher specific heat capacity, which can remove some heat from the contact point between the sand particles and the equipment wall upon contact. The higher sand particle concentration increases the contact frequency and contact area between the sand particles and the equipment wall, and the heat transfer pathway and heat dissipation efficiency are improved.

Unravelling the metabolic landscape of cutaneous melanoma: Insights from single-cell sequencing analysis and machine learning for prognostic assessment of lactate metabolism.

This manuscript presents a comprehensive investigation into the role of lactate metabolism-related genes as potential prognostic markers in skin cutaneous melanoma (SKCM). Bulk-transcriptome data from The Cancer Genome Atlas (TCGA) and GSE19234, GSE22153, and GSE65904 cohorts from GEO database were processed and harmonized to mitigate batch effects. Lactate metabolism scores were assigned to individual cells using the 'AUCell' package. Weighted Co-expression Network Analysis (WGCNA) was employed to identify gene modules correlated with lactate metabolism. Machine learning algorithms were applied to construct a prognostic model, and its performance was evaluated in multiple cohorts. Immune correlation, mutation analysis, and enrichment analysis were conducted to further characterize the prognostic model's biological implications. Finally, the function of key gene NDUFS7 was verified by cell experiments. Machine learning resulted in an optimal prognostic model, demonstrating significant prognostic value across various cohorts. In the different cohorts, the high-risk group showed a poor prognosis. Immune analysis indicated differences in immune cell infiltration and checkpoint gene expression between risk groups. Mutation analysis identified genes with high mutation loads in SKCM. Enrichment analysis unveiled enriched pathways and biological processes in high-risk SKCM patients. NDUFS7 was found to be a hub gene in the protein-protein interaction network. After the expression of NDUFS7 was reduced by siRNA knockdown, CCK-8, colony formation, transwell and wound healing tests showed that the activity, proliferation and migration of A375 and WM115 cell lines were significantly decreased. This study offers insights into the prognostic significance of lactate metabolism-related genes in SKCM.

Effects of magnesium sulfate combined with labetalol on inflammatory stress and pregnancy outcome of patients with gestational hypertension.

Gestational hypertension (GH) is a common disorder during pregnancy that can cause adverse pregnancy outcomes. In the present study, magnesium sulfate (MgSO4) combined with labetalol was used for clinical treatment. Randomized controlled trial was conducted in 100 patients with GH, documented in the Department of Obstetrics and Gynecology (Taicang TCM Hospital) grouped into the experimental (Expt) and control (Ctrl) groups (n=50 cases/group). The Ctrl group was treated with MgSO4, whereas the Expt group was treated with MgSO4 + labetalol. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the Expt group were not significantly different from those in the Ctrl group (P>0.05). By contrast, the SBP and DBP were significantly lower after treatment than those before treatment in both groups (P<0.05). Whole blood viscosity, plasma viscosity and hematocrit were significantly lower in the Expt group compared with those in the Ctrl group after treatment (P<0.05). High mobility group box-1 protein, homocysteine and serum cystatin C levels in the Expt group were also markedly lower than those in the Ctrl group after treatment (P<0.05). In the Expt group, the rate of spontaneous vaginal delivery was much higher, whereas the rates of cesarean section and postpartum hemorrhage were markedly lower than those in the Ctrl group (P<0.05). The occurrence of fetal intrauterine distress, placental abruption, neonatal asphyxia, premature birth and neonatal death were also significantly lower in the Expt group than those in the Ctrl group (P<0.05). In conclusion, MgSO4 + labetalol could improve inflammatory stress and the hemodynamics of patients with GH, and may have a marked antihypertensive effect. Thus, it may improve pregnancy outcome and reduce perinatal complications.

Rice's trajectory from wild to domesticated in East Asia.

Rice (Oryza sativa) serves as a staple food for more than one-third of the global population. However, its journey from a wild gathered food to domestication remains enigmatic, sparking ongoing debates in the biological and anthropological fields. Here, we present evidence of rice phytoliths sampled from two archaeological sites in China, Shangshan and Hehuashan, near the lower reaches of the Yangtze River. We demonstrate the growth of wild rice at least 100,000 years before present, its initial exploitation as a gathered resource at about 24,000 years before present, its predomestication cultivation at about 13,000 years before present, and eventually its domestication at about 11,000 years before present. These developmental stages illuminate a protracted process of rice domestication in East Asia and extend the continuous records of cereal evolution beyond the Fertile Crescent.

CDK5-USP30 signaling pathway regulates MAVS-mediated inflammation via suppressing mitophagy in MPTP/MPP+ PD model.

The discovery of MPTP, an industrial chemical and contaminant of illicit narcotics, which causes parkinsonism in humans, non-human primates and rodents, has led to environmental pollutants exposure being convicted as key candidate in Parkinson's disease (PD) pathogenesis. Though MPTP-induced mitochondrial dysfunction and neuroinflammation are mainly responsible for the causative issue of MPTP neurotoxicity, the underlying mechanism involved remains unclear. Here, we reveal a novel signaling mechanism of CDK5-USP30-MAVS regulating MPTP/MPP+ induced PD. MPP+ (the toxic metabolite of MPTP) treatment not only led to the increased protein levels of USP30 but also to mitophagy inhibition, mitochondrial dysfunction, and MAVS-mediated inflammation in BV2 microglial cells. Both mitophagy stimulation (Urolithin A administration) and USP30 knockdown relieved MAVS-mediated inflammation via restoring mitophagy and mitochondrial function in MPP+-induced cell model. Notably, MPTP/MPP+-induced CDK5 activation regulated USP30 phosphorylation at serine 216 to stabilize USP30. Moreover, CDK5-USP30 pathway promoted MAVS-mediated inflammation in MPTP/MPP+-induced PD model. Inhibition of CDK5 not only had a protective effect on MPP+-induced cell model of PD via suppressing the upregulation of USP30 and the activation of MAVS inflammation pathway in vitro, but also prevented neurodegeneration in vivo and alleviated movement impairment in MPTP mouse model of PD. Overall, our study reveal that CDK5 blocks mitophagy through phosphorylating USP30 and activates MAVS inflammation pathway in MPTP/MPP+-induced PD model, which suggests that CDK5-USP30-MAVS signaling pathway represents a valuable treatment strategy for PD induced by environmental neurotoxic pollutants in relation to MPTP.