The transcription factor NF-κB orchestrates nucleosome remodeling during the primary response to Toll-like receptor 4 signaling.

Inducible nucleosome remodeling at hundreds of latent enhancers and several promoters shapes the transcriptional response to Toll-like receptor 4 (TLR4) signaling in macrophages. We aimed to define the identities of the transcription factors that promote TLR-induced remodeling. An analysis strategy based on ATAC-seq and single-cell ATAC-seq that enriched for genomic regions most likely to undergo remodeling revealed that the transcription factor nuclear factor κB (NF-κB) bound to all high-confidence peaks marking remodeling during the primary response to the TLR4 ligand, lipid A. Deletion of NF-κB subunits RelA and c-Rel resulted in the loss of remodeling at high-confidence ATAC-seq peaks, and CRISPR-Cas9 mutagenesis of NF-κB-binding motifs impaired remodeling. Remodeling selectivity at defined regions was conferred by collaboration with other inducible factors, including IRF3- and MAP-kinase-induced factors. Thus, NF-κB is unique among TLR4-activated transcription factors in its broad contribution to inducible nucleosome remodeling, alongside its ability to activate poised enhancers and promoters assembled into open chromatin.

Aster-B-dependent estradiol synthesis protects female mice from diet-induced obesity.

Aster proteins mediate the nonvesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER). However, the importance of nonvesicular sterol movement for physiology and pathophysiology in various tissues is incompletely understood. Here we show that loss of Aster-B leads to diet-induced obesity in female but not in male mice, and that this sex difference is abolished by ovariectomy. We further demonstrate that Aster-B deficiency impairs nonvesicular cholesterol transport from the PM to the ER in ovaries in vivo, leading to hypogonadism and reduced estradiol synthesis. Female Aster-B-deficient mice exhibit reduced locomotor activity and energy expenditure, consistent with established effects of estrogens on systemic metabolism. Administration of exogenous estradiol ameliorates the diet-induced obesity phenotype of Aster-B-deficient female mice. These findings highlight the key role of Aster-B-dependent nonvesicular cholesterol transport in regulating estradiol production and protecting females from obesity.

A PPARγ/long noncoding RNA axis regulates adipose thermoneutral remodeling in mice.

Interplay between energy-storing white adipose cells and thermogenic beige adipocytes contributes to obesity and insulin resistance. Irrespective of specialized niche, adipocytes require the activity of the nuclear receptor PPARγ for proper function. Exposure to cold or adrenergic signaling enriches thermogenic cells though multiple pathways that act synergistically with PPARγ; however, the molecular mechanisms by which PPARγ licenses white adipose tissue to preferentially adopt a thermogenic or white adipose fate in response to dietary cues or thermoneutral conditions are not fully elucidated. Here, we show that a PPARγ/long noncoding RNA (lncRNA) axis integrates canonical and noncanonical thermogenesis to restrain white adipose tissue heat dissipation during thermoneutrality and diet-induced obesity. Pharmacologic inhibition or genetic deletion of the lncRNA Lexis enhances uncoupling protein 1-dependent (UCP1-dependent) and -independent thermogenesis. Adipose-specific deletion of Lexis counteracted diet-induced obesity, improved insulin sensitivity, and enhanced energy expenditure. Single-nuclei transcriptomics revealed that Lexis regulates a distinct population of thermogenic adipocytes. We systematically map Lexis motif preferences and show that it regulates the thermogenic program through the activity of the metabolic GWAS gene and WNT modulator TCF7L2. Collectively, our studies uncover a new mode of crosstalk between PPARγ and WNT that preserves white adipose tissue plasticity.

Demographics and Clinical Characteristics of Patients with Neurocysticercosis: A Retrospective Study from Dali, China.

Background: Neurocysticercosis (NCC), a predominant parasitic disease that affects the central nervous system and presents with diverse clinical manifestations, is a major contributor to acquired epilepsy worldwide, particularly in low-, middle-, and upper middle-income nations, such as China. In China, the Yunnan Province bears a significant burden of this disease. Objective: To describe the demographic, clinical, and radiological features as well as serum and cerebrospinal fluid antibodies to cysticercus in patients with NCC from Dali, Yunnan Province, China. Materials and Methods: This retrospective study included patients who were diagnosed with NCC at The First Affiliated Hospital of Dali University between January 2018 and May 2023 and were residing in Dali, Yunnan Province, China. Results: A total of 552 patients with NCC were included, of which 33.3% belonged to Bai ethnicity. The clinical presentation of NCC exhibited variability that was influenced by factors such as the number, location, and stage of the parasites. Epilepsy/seizure (49.9%) was the most prevalent symptom, with higher occurrence in the degenerative stage of cysts (P < 0.001). Compared with other locations, cysticerci located in the brain parenchyma are more likely to lead to seizures/epilepsy (OR = 17.45, 95% CI: 7.96-38.25) and headaches (OR = 3.02, 95% CI: 1.23-7.41). Seizures/epilepsy are more likely in patients with cysts in the vesicular (OR = 2.71, 95% CI: 1.12-6.61) and degenerative (OR = 102.38, 95% CI: 28.36-369.60) stages than those in the calcified stage. Seizures was not dependent on the number of lesions. All NCC patients underwent anthelminthic therapy, with the majority receiving albendazole (79.7%). Conclusion: This study provides valuable clinical insights into NCC patients in Dali and underscores the significance of NCC as a leading preventable cause of epilepsy.

Hybrid Functional Polymer-Enabled Multiplexed Chemosensor Patch for Wearable Adrenocortex Stress Profiling.

Measuring bioactive stress hormones, including cortisol and dehydroepiandrosterone (DHEA), allows for evaluating the hypothalamic-pituitary-adrenal (HPA) axis functioning, offering valuable insights into an individual's stress response through adrenocortex stress profiles (ASPs). Conventional methods for detecting steroid hormones involve sample collections and competitive immunoassays, which suffer from drawbacks such as time-consuming labeling and binding procedures, reliance on unstable biological receptors, and the need for sophisticated instruments. Here, we report a label-free and external redox reagent-free amperometric assay directly detecting sweat cortisol and DHEA levels on the skin. The approach utilizes multitarget sensors based on redox-active molecularly imprinted polymers (redox MIPs) capable of selectively binding cortisol and DHEA, inducing changes in electrochemical redox features. The redox MIP consists of imprinted cavities for specific capture of cortisol or DHEA in a poly(pyrrole-co-(dimethylamino)pyrrole) copolymer containing hydrophobic moieties to enhance affinity toward steroid hormones. The polymer matrix also incorporates covalently linked interpenetrating redox-active polyvinylferrocene, offering a stable electrochemical redox feature that enables sensitive current change in response to the target capture in the vicinity. The multiplexed sensor detects cortisol and DHEA within 5 min, with detection limits of 115 and 390 pM, respectively. Through the integration of redox MIP sensors into a wireless wearable sensing system, we successfully achieved ambulatory detection of these two steroid hormones in sweat directly on the skin. The new sensing method facilitates rapid, robust determination of the cortisol-DHEA ratio, providing a promising avenue for point-of-care assessment of an individual's physiological state.

Enzyme-Mimics for Sensitive and Selective Steroid Metabolite Detection.

We present an enzyme-like functional polymer that recognizes nonelectroactive targets and catalyzes their redox reactions for simple, selective steroid metabolite detection. Measuring steroid metabolites, such as cortisol, has been widely adopted to diagnose stress and chronic diseases. Conventional detection method based on competitive immunoassay requires time-consuming labeling processes for signal transduction and unstable biological receptors for biorecognition yet with limited selectivity. Inspired by natural enzymes' target specificity and catalytic nature, we report an enzyme-mimic using electrocatalytic molecularly imprinted polymers (EC-MIP) to achieve label-free, external redox reagent-free, sensitive, and selective electrochemical detection of cortisol. The EC-MIP sensor contains molecularly imprinted cavities for specific cortisol binding and embedded copper phthalocyanine tetrasulfonate (CuPcTS) for electrocatalytic reduction of the ketones on the captured cortisol into alcohols. The direct sensing approach resolves the intrinsic limitations of conventional MIP-based sensors, most notably the use of external redox probes and weak sensing signals. The sensor exhibited a detection limit of 181 pM with significantly enhanced selectivity using a differential sensing mechanism. The new enzyme-like sensor can be modified to detect other targets, offering a simple, robust approach to future health monitoring technologies.

Twenty years of ocean observations with China Argo.

The international Argo program, a global observational array of nearly 4 000 autonomous profiling floats initiated in the late 1990s, which measures the water temperature and salinity of the upper 2 000 m of the global ocean, has revolutionized oceanography. It has been recognized one of the most successful ocean observation systems in the world. Today, the proposed decade action "OneArgo" for building an integrated global, full-depth, and multidisciplinary ocean observing array for beyond 2020 has been endorsed. In the past two decades since 2002, with more than 500 Argo deployments and 80 operational floats currently, China has become an important partner of the Argo program. Two DACs have been established to process the data reported from all Chinese floats and deliver these data to the GDACs in real time, adhering to the unified quality control procedures proposed by the Argo Data Management Team. Several Argo products have been developed and released, allowing accurate estimations of global ocean warming, sea level change and the hydrological cycle, at interannual to decadal scales. In addition, Deep and BGC-Argo floats have been deployed, and time series observations from these floats have proven to be extremely useful, particularly in the analysis of synoptic-scale to decadal-scale dynamics. The future aim of China Argo is to build and maintain a regional Argo fleet comprising approximately 400 floats in the northwestern Pacific, South China Sea, and Indian Ocean, accounting for 9% of the global fleet, in addition to maintaining 300 Deep Argo floats in the global ocean (25% of the global Deep Argo fleet). A regional BGC-Argo array in the western Pacific also needs to be established and maintained.

Validation of a new method of providing case-specific time-of-death estimates using cadaver temperatures.

The near ubiquitous presence of numerical simulation has made case-specific calculations of body temperatures following death possible so that accurate calculations of body temperatures can provide valuable information for estimating the time of death and can aid in forensic investigations. Here, a computational approach is described that has been validated against multiple, independent, and experimental investigations. The approach only requires one subjective input parameter (the heat transfer coefficient). A simple algorithm serves as a guidepost to the selection of this parameter. The algorithm incorporates clothing and the space in which the body is housed. Heat transfer coefficients that range from h = 2 W/m2 /°C for bodies that are heavily clothed to h = 9 W/m2 /°C for bodies that are nude (in air). The method also requires setting of ambient temperature conditions (ambient temperature)-however, that input is often available. The paucity of inputs makes this technique remarkably easy to employ. The new method is also able to calculate cadaver cooling rates for situations where the cadaver is in a timewise or spatially changing thermal environment (diurnal temperature variations, bodies partially submerged in water, changes to weather, insolation, etc.). Results from the present calculations are compared with a large body of measurements from the literature; it was found that the predictions and measurements were in excellent agreement, regardless of the ambient temperature conditions and the nature of the clothing of the body. This new calculation approach can be used with reasonable accuracy for determining cadaver cooling and time since death.

Another Year of Record Heat for the Oceans.

Changes in ocean heat content (OHC), salinity, and stratification provide critical indicators for changes in Earth's energy and water cycles. These cycles have been profoundly altered due to the emission of greenhouse gasses and other anthropogenic substances by human activities, driving pervasive changes in Earth's climate system. In 2022, the world's oceans, as given by OHC, were again the hottest in the historical record and exceeded the previous 2021 record maximum. According to IAP/CAS data, the 0-2000 m OHC in 2022 exceeded that of 2021 by 10.9 ± 8.3 ZJ (1 Zetta Joules = 1021 Joules); and according to NCEI/NOAA data, by 9.1 ± 8.7 ZJ. Among seven regions, four basins (the North Pacific, North Atlantic, the Mediterranean Sea, and southern oceans) recorded their highest OHC since the 1950s. The salinity-contrast index, a quantification of the "salty gets saltier-fresh gets fresher" pattern, also reached its highest level on record in 2022, implying continued amplification of the global hydrological cycle. Regional OHC and salinity changes in 2022 were dominated by a strong La Niña event. Global upper-ocean stratification continued its increasing trend and was among the top seven in 2022.

Parkin regulates adiposity by coordinating mitophagy with mitochondrial biogenesis in white adipocytes.

Parkin, an E3 ubiquitin ligase, plays an essential role in mitochondrial quality control. However, the mechanisms by which Parkin connects mitochondrial homeostasis with cellular metabolism in adipose tissue remain unclear. Here, we demonstrate that Park2 gene (encodes Parkin) deletion specifically from adipose tissue protects mice against high-fat diet and aging-induced obesity. Despite a mild reduction in mitophagy, mitochondrial DNA content and mitochondrial function are increased in Park2 deficient white adipocytes. Moreover, Park2 gene deletion elevates mitochondrial biogenesis by increasing Pgc1α protein stability through mitochondrial superoxide-activated NAD(P)H quinone dehydrogenase 1 (Nqo1). Both in vitro and in vivo studies show that Nqo1 overexpression elevates Pgc1α protein level and mitochondrial DNA content and enhances mitochondrial activity in mouse and human adipocytes. Taken together, our findings indicate that Parkin regulates mitochondrial homeostasis by balancing mitophagy and Pgc1α-mediated mitochondrial biogenesis in white adipocytes, suggesting a potential therapeutic target in adipocytes to combat obesity and obesity-associated disorders.

Reconfigurable photoinduced terahertz wave modulation using hybrid metal-silicon metasurface.

We present a photoinduced reconfigurable metasurface to enable high spatial resolution terahertz (THz) wave modulation. Conventional photoinduced THz wave modulation uses optically induced conductive patterns on a semiconductor substrate to create programmable passive THz devices. The technique, albeit versatile and straightforward, suffers from limited performance resulting from the severe lateral diffusion of the photogenerated carriers that undermines the spatial resolution and conductivity contrast of the photoinduced conductive patterns. The proposed metasurface overcomes the limitation using a metal-jointed silicon mesa array with subwavelength-scaled dimensions on an insulator substrate. The structure physically restrains the lateral diffusion of the photogenerated carriers while ensuring the electrical conductivity between the silicon mesas , which is essential for THz wave modulation. The metasurface creates high-definition photoconductive patterns with dimensions smaller than the diffusion length of photogenerated carriers. The metasurface provides a modulation depth of -20 to -10 dB for the THz waves between 0.2 to 1.2 THz and supports a THz bandpass filter with a tunable central frequency. The new, to the best of our knowledge, design concept will benefit the implementation of reconfigurable THz devices.

Ferrocene-Grafted Carbon Nanotubes for Sensitive Non-Enzymatic Electrochemical Detection of Hydrogen Peroxide.

Sensitive detection of hydrogen peroxide (H2O2) residue in aseptic packaging at point of use is critical to food safety. We present a sensitive non-enzymatic, amperometric H2O2 sensor based on ferrocene-functionalized multi-walled carbon nanotubes (MWCNT-FeC) and facile screen-printed carbon electrodes (SPCEs). The sensor utilizes the covalently grafted ferrocene as an effective redox mediator and the MWCNT networks to provide a large active surface area for efficient electrocatalytic reactions. The electrocatalytic MWCNT-FeC modified electrodes feature a high-efficiency electron transfer and a high electrocatalytic activity towards H2O2 reduction at a low potential of -0.15 V vs. Ag/AgCl. The decreased operating potential improves the selectivity by inherently eliminating the cross-reactivity with other electroactive interferents, such as dopamine, glucose, and ascorbic acid. The sensor exhibits a wide linear detection range from 1 µM to 1 mM with a detection limit of 0.49 µM (S/N=3). The covalently functionalized electrodes offered highly reproducible and reliable detection, providing a robust property for continuous, real-time H2O2 monitoring. Furthermore, the proposed sensor was successfully employed to determine H2O2 levels in spiked packaged milk and apple juice with satisfactory recoveries (94.33-97.62%). The MWCNT-FeC modified SPCEs offered a facile, cost-effective method for highly sensitive and selective point-of-use detection of H2O2.

Nano gold-doped molecularly imprinted electrochemical sensor for rapid and ultrasensitive cortisol detection.

Rapid and sensitive detection of steroid hormone cortisol can benefit the diagnosis of diseases related to adrenal gland disorders and chronic stress. We report a molecularly imprinted polymer (MIP)-based electrochemical sensor that utilized nano gold-doped poly o-phenylenediamine (poly-o-PD) film to selectively determine trace level cortisol with enhanced sensitivity. The sensor detected cortisol levels by measuring the current change of the redox-active probes in response to the binding of target cortisol to the imprinted sites in the polymer. The gold-doped MIP (Au@MIP) sensor was prepared using a facile one-step in situ gold reduction and electropolymerization method to distribute high-density gold nanoparticles in the vicinity of the binding cavities. The in situ gold reduction promote the polymerization reaction, enlarging the effective surface area of the sensor. The nano gold doping also facilitated charge transfer when exposed to redox reagents. It enabled efficient blocking of the charge transfer upon the occupation of the cavities by cortisol, resulting in enhanced detection response and sensitivity. The Au@MIP sensor exhibited a high affinity toward cortisol binding with a dissociation constant Kd of ∼0.47 nM, a linear detection range from 1 pM to 500 nM with a detection limit of ∼200 fM, and satisfied specificity over other steroid hormones with highly similar structures. The sensor was successfully demonstrated to determine cortisol levels in spiked saliva in normal and elevated ranges. The facile antibody-free cortisol detection method was proved to be highly sensitive and selective, suitable for point-of-care testing applications.

Using cadaver temperatures to estimate time of death: A case-specific numerical approach.

A new approach is taken to estimating the time of death based on cadaver temperatures. The predictions are obtained by using numerical simulation that can be performed in a case-by-case scenario. Such a method enables time-of-death predictions for persons of any size and weight and in any thermal environment. An added advantage of the method is that it is not dependent upon an identification of the individual tissue layers and regions. Rather, a homogeneous tissue model is used, and the results that are obtained agree closely with the results of prior estimation methods and also with a prior published case study. Among the results presented in this study are various convective environments in both air and water (or a combination for a partially submerged body). The orientation of the body (face down vs face up) is investigated. It is found that when a body is face up, its body core temperature is more responsive to the ambient conditions, compared with a face-down orientation, at least for some partial-submergence depths. The method disclosed here can also be used to handle situations, where the environmental conditions are changing (such as diurnal temperature variations, variation in cloudy or sunny skies, etc.). Current nomogram methods are not able to handle such timewise variations.

Another Record: Ocean Warming Continues through 2021 despite La Niña Conditions.

The increased concentration of greenhouse gases in the atmosphere from human activities traps heat within the climate system and increases ocean heat content (OHC). Here, we provide the first analysis of recent OHC changes through 2021 from two international groups. The world ocean, in 2021, was the hottest ever recorded by humans, and the 2021 annual OHC value is even higher than last year's record value by 14 ± 11 ZJ (1 zetta J = 1021 J) using the IAP/CAS dataset and by 16 ± 10 ZJ using NCEI/NOAA dataset. The long-term ocean warming is larger in the Atlantic and Southern Oceans than in other regions and is mainly attributed, via climate model simulations, to an increase in anthropogenic greenhouse gas concentrations. The year-to-year variation of OHC is primarily tied to the El Niño-Southern Oscillation (ENSO). In the seven maritime domains of the Indian, Tropical Atlantic, North Atlantic, Northwest Pacific, North Pacific, Southern oceans, and the Mediterranean Sea, robust warming is observed but with distinct inter-annual to decadal variability. Four out of seven domains showed record-high heat content in 2021. The anomalous global and regional ocean warming established in this study should be incorporated into climate risk assessments, adaptation, and mitigation.

Identification of an IFN-ß-associated gene signature for the prediction of overall survival among glioblastoma patients.

BACKGROUND: Brain glioblastoma multiforme (GBM) is the most common primary malignant intracranial tumor. The prognosis of this disease is extremely poor. While the introduction of ß-interferon (IFN-ß) regimen in the treatment of gliomas has significantly improved the outcome of patients; The mechanism by which IFN-ß induces increased TMZ sensitivity has not been described. Therefore, the main objective of the study was to elucidate the molecular mechanisms responsible for the beneficial effect of IFNß in GBM. METHODS: Messenger RNA expression profiles and clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA) GBM and GSE83300 dataset from the Gene Expression Omnibus. Univariate Cox regression analysis and lasso Cox regression model established a novel 4-gene IFN-ß signature (peroxiredoxin 1, Sec61 subunit beta, X-ray repair cross-complementing 5, and Bcl-2-like protein 2) for GBM prognosis prediction. Further, GBM samples (n=50) and normal brain tissues (n=50) were then used for real-time polymerase chain reaction experiments. Gene set enrichment analysis (GSEA) was performed to further understand the underlying molecular mechanisms. Pearson correlation was applied to calculate the correlation between the long non-coding RNAs (lncRNAs) and IFN-ß-associated genes. An lncRNA with a correlation coefficient |R2|>0.3 and P<0.05 was considered to be an IFN-ß-associated lncRNA. RESULTS: Patients in the high-risk group had significantly poorer survival than patients in the low-risk group. The signature was found to be an independent prognostic factor for GBM survival. Furthermore, GSEA revealed several significantly enriched pathways, which might help explain the underlying mechanisms. Our study identified a novel robust 4-gene IFN-ß signature for GBM prognosis prediction. The signature might contain potential biomarkers for metabolic therapy and treatment response prediction for GBM patients. CONCLUSIONS: In the present study, we established a novel IFN-ß-associated gene signature to predict the overall survival of GBM patients, which may help in clinical decision making for individual treatment.

Reduced Amygdala Microglial Expression of Brain-Derived Neurotrophic Factor and Tyrosine Kinase Receptor B (TrkB) in a Rat Model of Poststroke Depression.

BACKGROUND Previous studies have implicated reduced brain-derived neurotrophic factor (BDNF) expression and BDNF-TrkB receptor signaling as well as microglial activation and neuroinflammation in poststroke depression (PSD). However, the contributions of microglial BDNF-TrkB signaling to PSD pathogenesis are unclear. MATERIAL AND METHODS We compared depression-like behaviors as well as neuronal and microglial BDNF and TrkB expression levels in the amygdala, a critical mood-relating limbic structure, in rat models of stroke, depression, and PSD. Depression-like behaviors were assessed using the sucrose preference test, open-field test, and weight measurements, while immunofluorescence double staining was employed to estimate BDNF and TrkB expression by CD11b-positive amygdala microglia and NeuN-positive amygdala neuron. Another group of PSD model rats were examined following daily intracerebroventricular injection of proBDNF, tissue plasminogen activator (t-PA), or normal saline (NS) for 7 days starting 4 weeks after chronic unpredictable mild stress (CUMS). RESULTS The numbers of BDNF/CD11b- and TrkB/CD11b-immunofluorescence-positive cells were lowest in the PSD group at 4 and 8 weeks after CUMS (P0.05). Injection of t-PA increased BDNF/CD11b- and TrkB/CD11b-positive cells in the amygdala of PSD rats and normalized behavior compared with NS or proBDNF injection (P<0.05). In contrast, proBDNF injection reduced BDNF and TrkB expression compared with NS (P<0.05). CONCLUSIONS These results suggest that decreased BDNF and TrkB expression by amygdala microglia may contribute to PSD pathogenesis and depression-like behaviors.

The causes of sea-level rise since 1900.

The rate of global-mean sea-level rise since 1900 has varied over time, but the contributing factors are still poorly understood1. Previous assessments found that the summed contributions of ice-mass loss, terrestrial water storage and thermal expansion of the ocean could not be reconciled with observed changes in global-mean sea level, implying that changes in sea level or some contributions to those changes were poorly constrained2,3. Recent improvements to observational data, our understanding of the main contributing processes to sea-level change and methods for estimating the individual contributions, mean another attempt at reconciliation is warranted. Here we present a probabilistic framework to reconstruct sea level since 1900 using independent observations and their inherent uncertainties. The sum of the contributions to sea-level change from thermal expansion of the ocean, ice-mass loss and changes in terrestrial water storage is consistent with the trends and multidecadal variability in observed sea level on both global and basin scales, which we reconstruct from tide-gauge records. Ice-mass loss-predominantly from glaciers-has caused twice as much sea-level rise since 1900 as has thermal expansion. Mass loss from glaciers and the Greenland Ice Sheet explains the high rates of global sea-level rise during the 1940s, while a sharp increase in water impoundment by artificial reservoirs is the main cause of the lower-than-average rates during the 1970s. The acceleration in sea-level rise since the 1970s is caused by the combination of thermal expansion of the ocean and increased ice-mass loss from Greenland. Our results reconcile the magnitude of observed global-mean sea-level rise since 1900 with estimates based on the underlying processes, implying that no additional processes are required to explain the observed changes in sea level since 1900.

Dencichine ameliorates renal injury by improving oxidative stress, apoptosis and fibrosis in diabetic rats.

OBJECTIVE: To investigate protective efficacies and mechanisms of dencichine on diabetic kidney injury via in vitro and in vivo assays. METHODS: Effects of dencichine on hydrogen peroxide (H2O2) induced oxidative damage in HK-2 renal cells were assessed by CCK-8 method. Forty streptozotocin (STZ)-induced diabetic rats with kidney injury were randomly divided into negative control group, three doses of dencichine (40, 80 and 160 mg/kg) groups. Blood biochemical and kidney related indexes as well adrenal morphological changes, apoptosis and autophagy related markers of diabetic rats were measured. RESULTS: Cell viability of HK-2 cells with oxidative damage induced by H2O2 was significantly improved by dencichine with 160 µg/mL for 43.7% and 320 µg/mL for 52.9% compared with control. Moreover, the decreased reactive oxygen species (ROS), and increased intracellular antioxidant enzymes including GPX1, SOD2 and GSH were showed in dencichine groups. In addition, incubation of dencichine in HK-2 cells promoted the increase of p-AMPK, BCL2, LC3, decreased activation of p-mTOR, BAX and Caspase 3. Chronic treatment of dencichine improved the STZ-induced diabetic characteristics of model rats. Further histopathological examination of renal tissues revealed 12-week treatment of dencichine effectively improved the morphology of nephropathy in diabetic rats. Moreover, dencichine also ameliorated excessive oxidation stress, down-regulated renal cell apoptosis and fibrosis related proteins, thereby protected renal tissues in diabetic rats. CONCLUSION: Dencichine ameliorated STZ-induced kidney injury mainly through inhibiting oxidative stress, reducing renal fibrosis, increasing autophagy, and reducing the renal cell apoptosis related proteins to protect nephrocytes and decrease renal tissue damage.

Using heat to kill SARS-CoV-2.

The current coronavirus pandemic has reached global proportions and requires unparalleled collective and individual efforts to slow its spread. One critically important issue is the proper sterilization of physical objects that have been contaminated by the virus. Here, we review the currently existing literature on thermal inactivation of coronavirus (SARS-CoV-2) and present preliminary guideless on temperatures and exposure durations required to sterilize. We also compare these temperatures/exposure durations with potential household appliances that may be thought capable of performing sterilization.