Macrophage-derived exosomes promote telomere fragility and senescence in tubular epithelial cells by delivering miR-155.

BACKGROUND: Chronic kidney disease (CKD) is highly prevalent worldwide, and its global burden is substantial and growing. CKD displays a number of features of accelerated senescence. Tubular cell senescence is a common biological process that contributes to CKD progression. Tubulointerstitial inflammation is a driver of tubular cell senescence and a common characteristic of CKD. However, the mechanism by which the interstitial inflammation drives tubular cell senescence remains unclear. This paper aims to explore the role of exosomal miRNAs derived from macrophages in the development of tubular cell senescence. METHODS: Among the identified inflammation-related miRNAs, miR-155 is considered to be one of the most important miRNAs involved in the inflammatory response. Macrophages, the primary immune cells that mediate inflammatory processes, contain a high abundance of miR-155 in their released exosomes. We assessed the potential role of miR-155 in tubular cell senescence and renal fibrosis. We subjected miR-155-/- mice and wild-type controls, as well as tubular epithelial cells (TECs), to angiotensin II (AngII)-induced kidney injury. We assessed kidney function and injury using standard techniques. TECs were evaluated for cell senescence and telomere dysfunction in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization. RESULTS: Compared with normal controls, miR-155 was up-regulated in proximal renal tubule cells in CKD patients and mouse models of CKD. Moreover, the expression of miR-155 was positively correlated with the extent of renal fibrosis, eGFR decline and p16INK4A expression. The overexpression of miR-155 exacerbated tubular senescence, evidenced by increased detection of p16INK4A/p21expression and senescence-associated ß-galactosidase activity. Notably, miR-155 knockout attenuates renal fibrosis and tubule cell senescence in vivo. Interestingly, once released, macrophages-derived exosomal miR-155 was internalized by TECs, leading to telomere shortening and dysfunction through targeting TRF1. A dual-luciferase reporter assay confirmed that TRF1 was the direct target of miR-155. Thus, our study clearly demonstrates that exosomal miR-155 may mediate communication between macrophages and TECs, subsequently inducing telomere dysfunction and senescence in TECs. CONCLUSIONS: Our work suggests a new mechanism by which macrophage exosomes are involved in the development of tubule senescence and renal fibrosis, in part by delivering miR-155 to target TRF1 to promote telomere dysfunction. Our study may provide novel strategies for the treatment of AngII-induced kidney injury.

In vivo CRISPR gene editing in patients with herpetic stromal keratitis.

In vivo CRISPR gene therapy holds large clinical potential, but the safety and efficacy remain largely unknown. Here, we injected a single dose of herpes simplex virus 1 (HSV-1)-targeting CRISPR formulation in the cornea of three patients with severe refractory herpetic stromal keratitis (HSK) during corneal transplantation. Our study is an investigator-initiated, open-label, single-arm, non-randomized interventional trial at a single center (NCT04560790). We found neither detectable CRISPR-induced off-target cleavages by GUIDE-seq nor systemic adverse events for 18 months on average in all three patients. The HSV-1 remained undetectable during the study. Our preliminary clinical results suggest that in vivo gene editing targeting the HSV-1 genome holds acceptable safety as a potential therapy for HSK.

Separation of astragaloside IV from Astragalus membranaceus based on high-speed countercurrent chromatography in continuous injection mode.

INTRODUCTION: Astragaloside IV (AS-IV) is an index for the quality evaluation of the traditional Chinese medicine Astragalus and an important material basis for Astragalus to exert its medicinal effects, and it is difficult to obtain a single AS-IV by ordinary separation methods. OBJECTIVE: To find a new isolation method that can prepare AS-IV quickly and efficiently. METHODOLOGY: AS-IV was isolated from Astragalus membranaceus extract by high-speed countercurrent chromatography using a two-phase solvent system consisting of ethyl acetate/n-butanol/water (4.2:0.8:5, v/v) at a speed of 950 rpm at a flow rate of 2 mL/min using one of the high-speed countercurrent chromatographic sequential injection models developed during the previous study. RESULTS: Compared with the common countercurrent chromatographic separation, this separation method increased the injection volume and yield by 4-fold and 4.47-fold, respectively, with only about 1.2-fold increase in solvent consumption and separation time, and the purity was basically not reduced, and 55.9 mg of AS-IV, with a purity of 96.95%, was finally prepared from 400 mg of the crude extract in 240 min. CONCLUSION: The continuous injection mode of high-speed countercurrent chromatography was able to successfully prepare a large amount of AS-IV with high purity at one time.

Au-Seeded CsPbI3 Nanowire Optoelectronics via Exothermic Nucleation.

Converting vapor precursors to solid nanostructures via a liquid noble-metal seed is a common vapor deposition principle. However, such a noble-metal-seeded process is excluded from the crystalline halide perovskite synthesis, mainly hindered by the growth mechanism shortness. Herein, powered by a spontaneous exothermic nucleation process (ΔH < 0), the Au-seeded CsPbI3 nanowires (NWs) growth is realized based on a vapor-liquid-solid (VLS) growth mode. It is energetically favored that the Au seeds are reacted with a Pb vapor precursor to form molten Au-Pb droplets at temperatures down to 212 °C, further triggering the low-temperature VLS growth of CsPbI3 NWs. More importantly, this Au-seeded process reduces in-bandgap trap states and consequently avoids Shockley-Read-Hall recombination, contributing to outstanding photodetector performances. Our work extends the powerful Au-seeded VLS growth mode to the emerging halide perovskites, which will facilitate their nanostructures with tailored material properties.

Controlling Surface Chemical Inhomogeneity of Ni2 P/MoNiP2 /MoP Heterostructure Electrocatalysts for Efficient Hydrogen Evolution Reaction.

Crystalline/amorphous phase engineering is demonstrated as a powerful strategy for electrochemical performance optimization. However, it is still a considerable challenge to prepare transition metal-based crystalline/amorphous heterostructures because of the low redox potential of transition metal ions. Herein, a facile H2 -assisted method is developed to prepare ternary Ni2 P/MoNiP2 /MoP crystalline/amorphous heterostructure nanowires on the conductive substrate. The characterization results show that the content of the MoNiP2 phase and the crystallinity of the MoP phase can be tuned by simply controlling the H2 concentration. The obtained electrocatalyst exhibits a superior alkaline hydrogen evolution reaction performance, delivering overpotentials of 20 and 76 mV to reach current densities of 10 and 100 mA cm-2 with a Tafel slope of 30.6 mV dec-1 , respectively. The catalysts also reveal excellent stability under a constant 100 h operation, higher than most previously reported electrocatalysts. These striking performances are ascribed to the optimized hydrogen binding energy and favorable hydrogen adsorption/desorption kinetics. This work not only exhibits the potential application of ternary Ni2 P/MoNiP2 /MoP crystalline/amorphous heterostructure nanowires catalysts for practical electrochemical water splitting, but also paves the way to prepare non-noble transition metal-based electrocatalysts with optimized crystalline/amorphous heterostructures.

The acceptance of SARS-CoV-2 rapid antigen self-testing: A cross-sectional study in China.

Compared with the nucleic acid amplification test (NATT), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapid antigen self-testing (RAST) has advantages in speed and convenience. However, little is known about people's acceptance and influencing factors for SARS-CoV-2 RAST. A cross-sectional study was conducted from April 21 to 30, 2022 in China. The χ2 test and multivariate logistic regressions were used to identify the influencing factors. The structural equation model was used to test the extended protective motivation theory (PMT) model hypotheses. Among the total of 5107 participants, 62.5% were willing to accept the SARS-CoV-2 RAST. There were significant differences in acceptance among different residences (p < 0.001), educational level (p < 0.001), occupation (p < 0.001), monthly income (p < 0.001), travel frequency (p < 0.05), and feelings about NATT (p < 0.001). Response efficacy (ß = 0.05; p = 0.025) and self-efficacy (ß = 0.84; p < 0.001) had a positive effect, while response cost showed a negative effect (ß = -0.07; p < 0.001). The public's major concerns about SARS-CoV-2 RAST are its reliability, testing method, price, and authority. Overall, a moderate intention to use SARS-CoV-2 RAST was found among the Chinese population. The extended PMT can be used for the prediction of intention to accept the RAST. We need to take measures to increase people's acceptance of SARS-CoV-2 RAST.

Characteristics of genotype, drug resistance, and molecular transmission network among newly diagnosed HIV-1 infections in Shenzhen, China.

The HIV-1 pandemic has persisted for four decades, and poses a major challenge to global public health. Shenzhen, a city with large number of migrant populations in China, is suffering HIV-1 epidemic. It is necessary to continuously conduct the molecular surveillance among newly diagnosed HIV-1 patients in these migrant population. In this study, plasma samples of newly diagnosed and ART-naive HIV-1 infections were collected from Shenzhen city in China. The partial genes of HIV-1 gag and pol were amplified and sequenced for the analysis of genotype, drug resistance, and molecular transmission network. Ninety-one sequences of pol gene were obtained from newly diagnosed HIV-1 infections in Shenzhen, and seven HIV-1 subtypes were revealed in this investigation. Among them, the circulating recombinant form (CRF) 07_BC was the mostly frequent subtype (53.8%, 49/91), followed by CRF01_AE (20.9%, 19/91), CRF55_01B (9.9%, 9/91), unique recombinant forms (URFs) (8.8%, 8/91), B (3.3%, 3/91), CRF59_01B (2.2%, 2/91), and CRF08_BC (1.1%, 1/91). The overall prevalence of pretreatment drug resistance (PDR) was 23.1% (21/91), and 52.38% (11/21) of the PDR was specific for the nonnucleotide reverse transcriptase inhibitors (NNRTIs). Furthermore, a total of 3091 pol gene sequences were used to generate 19 molecular transmission clusters, and then one growing cluster, a new cluster, and a cluster with growth reactivation were identified. The result revealed that more sexual partner, CRF_07BC subtype, and seven amino acid deletions in gag p6 region might be the influencing factors associated with the high risk of transmission behavior. Compared with CRF01_AE subtype, CRF07_BC subtype strains were more likely to form clusters in molecular transmission network. This suggests that long-term surveillance of the HIV-1 molecular transmission should be a critical measure to achieve a precise intervention for controlling the spread of HIV-1 in China.

Quercetin alleviates tubulointerstitial inflammation by inhibiting exosomes-mediated crosstalk between tubular epithelial cells and macrophages.

BACKGROUND: Tubulointerstitial inflammation (TII) is a critical pathological feature of kidney disease leading to renal fibrosis, and its treatment remains a major clinical challenge. We sought to explore the role of quercetin, a potential exosomes inhibitor, in exosomes release and TII. METHODS: The effects of quercetin on exosomes release and TII were examined by two TII mouse models: the unilateral ureteral obstruction (UUO) models and the LPS-induced mouse models. In vitro, exosomes-mediated crosstalk between tubular epithelial cells (TECs) and macrophages was performed to investigate the mechanisms by which quercetin inhibited exosomes and TII. RESULTS: In this study, we found that exosomes-mediated crosstalk between TECs and macrophages contributed to the development of TII. In vitro, exosomes released from LPS-stimulated TECs induced increased expression of inflammatory cytokines and fibrotic markers in Raw264·7 cells and vice versa. Interestingly, heat shock protein 70 (Hsp70) or Hsp90 proteins could control exosomes release from TECs and macrophages both in vivo and in vitro. Importantly, quercetin, a previously recognized heat shock protein inhibitor, could significantly reduce exosomes release in TII models by down-regulating Hsp70 or Hsp90. Quercetin abrogated exosomes-mediated intercellular communication, which attenuated TII and renal fibrosis accordingly. CONCLUSION: Quercetin could serve as a novel strategy for treatment of tubulointerstitial inflammation by inhibiting the exosomes-mediated crosstalk between tubules and macrophages.

Synthesis of Imidazo[1,2-a]pyridine-Fused 1,3-Benzodiazepine Derivatives with Anticancer Activity via a One-Pot Cascade GBB-3CR/Pd(II)-Catalyzed Azide-Isocyanide Coupling/Cyclization Process.

A new one-pot synthesis of imidazo[1,2-a]pyridine-fused 1,3-benzodiazepine derivatives via a sequential GBB-3CR/Pd(II)-catalyzed azide-isocyanide coupling/cyclization process was developed. The Groebke-Blackburn-Bienaymé three-component reactions (GBB-3CR) of 2-aminopyridine, 2-azidobenzaldehydes, and isocyanides in the presence of a catalytic amount of p-toluenesulfonic acid gave azide intermediates without separation. The reaction was followed by using another molecule of isocyanides to produce imidazo[1,2-a]pyridine-fused 1,3-benzodiazepine derivatives in good yields by the Pd(II)-catalyzed azide-isocyanide coupling/cyclization reaction. The synthetic approach produces novel nitrogen-fused polycyclic heterocycles under mild reaction conditions. The preliminary biological evaluation demonstrated that compound 6a inhibited glioma cells efficiently, suggesting potentially broad applications of the approach for synthesis and medicinal chemistry.

Tubular-specific CDK12 knockout causes a defect in urine concentration due to premature cleavage of the slc12a1 gene.

Cyclin-dependent kinase 12 (CDK12) plays a critical role in regulating gene transcription. CDK12 inhibition is a potential anticancer therapeutic strategy. However, several clinical trials have shown that CDK inhibitors might cause renal dysfunction and electrolyte disorders. CDK12 is abundant in renal tubular epithelial cells (RTECs), but the exact role of CDK12 in renal physiology remains unclear. Genetic knockout of CDK12 in mouse RTECs causes polydipsia, polyuria, and hydronephrosis. This phenotype is caused by defects in water reabsorption that are the result of reduced Na-K-2Cl cotransporter 2 (NKCC2) levels in the kidney. In addition, CKD12 knockout causes an increase in Slc12a1 (which encodes NKCC2) intronic polyadenylation events, which results in Slc12a1 truncated transcript production and NKCC2 downregulation. These findings provide novel insight into CDK12 being necessary for maintaining renal homeostasis by regulating NKCC2 transcription, which explains the critical water and electrolyte disturbance that occurs during the application of CDK12 inhibitors for cancer treatment. Therefore, there are safety concerns about the clinical use of these new anticancer drugs.

Substituent Effect to Fine-Tune Energy Levels of Atom-Precise [MoOS3 ]2- Modified Copper(I) Thiolate Clusters Boosting Recyclable Photocatalysis.

The propulsion of photocatalytic hydrogen (H2 ) production is limited by the rational design and regulation of catalysts with precise structures and excellent activities. In this work, the [MoOS3 ]2- unit is introduced into the CuI clusters to form a series of atomically-precise MoVI -CuI bimetallic clusters of [Cu6 (MoOS3 )2 (C6 H5 (CH2 )S)2 (P(C6 H4 -R)3 )4 ] ⋅ xCH3 CN (R=H, CH3 , or F), which show high photocatalytic H2 evolution activities and excellent stability. By electron push-pull effects of the surface ligand, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) levels of these MoVI -CuI clusters can be finely tuned, promoting the resultant visible-light-driven H2 evolution performance. Furthermore, MoVI -CuI clusters loaded onto the surface of magnetic Fe3 O4 carriers significantly reduced the loss of catalysts in the collection process, efficiently addressing the recycling issues of such small cluster-based catalyst. This work not only highlights a competitively universal approach on the design of high-efficiency cluster photocatalysts for energy conversion, but also makes it feasible to manipulate the catalytic performance of clusters through a rational substituent strategy.

Emodin alleviates arthritis pain through reducing spinal inflammation and oxidative stress.

Chronic pain is the predominant problem for rheumatoid arthritis patients, and negatively affects quality of life. Arthritis pain management remains largely inadequate, and developing new treatment strategies are urgently needed. Spinal inflammation and oxidative stress contribute to arthritis pain and represent ideal targets for the treatment of arthritis pain. In the present study, collagen-induced arthritis (CIA) mouse model was established by intradermally injection of type II collagen (CII) in complete Freund's adjuvant (CFA) solution, and exhibited as paw and ankle swelling, pain hypersensitivity and motor disability. In spinal cord, CIA inducement triggered spinal inflammatory reaction presenting with inflammatory cells infiltration, increased Interleukin-1ß (IL-1ß) expression, and up-regulated NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and cleaved caspase-1 levels, elevated spinal oxidative level presenting as decreased nuclear factor E2-related factor 2 (Nrf2) expression and Superoxide dismutase (SOD) activity. To explore potential therapeutic options for arthritis pain, emodin was intraperitoneally injected for 3 days on CIA mice. Emodin treatment statistically elevated mechanical pain sensitivity, suppressed spontaneous pain, recovered motor coordination, decreased spinal inflammation score and IL-1ß expression, increased spinal Nrf2 expression and SOD activity. Further, AutoDock data showed that emodin bind to Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) through two electrovalent bonds. And emodin treatment increased the phosphorylated AMPK at threonine 172. In summary, emodin treatment activates AMPK, suppresses NLRP3 inflammasome response, elevates antioxidant response, inhibits spinal inflammatory reaction and alleviates arthritis pain.

Acceptance of COVID-19 booster vaccination based on the protection motivation theory: A cross-sectional study in China.

The promotion of the booster shots against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an open issue to be discussed. Little is known about the public intention and the influencing factors regarding the booster vaccine. A cross-sectional survey in Chinese adults was conducted using an online questionnaire, which designed on the basis of protection motivation theory (PMT) scale and vaccine hesitancy scale (VHS). Hierarchical multiple regression was used to compare the fitness of the PMT scale and VHS for predicting booster vaccination intention. Multivariable logistic regression was used to analyze the factors associated with the acceptance. Six thousand three hundred twenty-one (76.8%) of participants were willing to take the booster shot. However, the rest of the participants (23.2%) were still hesitant to take the booster vaccine. The PMT scale was more powerful than the VHS in explaining the vaccination intention. Participants with high perceived severity (adjusted odds ratio [aOR] = 0.69) and response cost (aOR = 0.47) were less willing to take the booster shots, but participants with high perceived susceptibility (aOR = 1.19), response efficacy (aOR = 2.13), and self-efficacy (aOR = 3.33) were more willing to take the booster shots. In summary, interventions based on PMT can provide guidance to ensure the acceptance of the booster vaccine.

Efficient Capture and Separation of Cancer Cells Using Hyaluronic Acid-Modified Magnetic Beads in a Microfluidic Chip.

The efficient isolation and specific discrimination of circulating tumor cells (CTCs) is expected to provide valuable information for understanding tumor metastasis and play an important role in the treatment of cancer patients. In this study, we developed a novel and rapid method for efficient capture and specific identification of cancer cells using hyaluronic acid (HA)-modified SiO2-coated magnetic beads in a microfluidic chip. First, polyacrylamide-surfaced SiO2-coated magnetic beads (SiO2@MBs) were covalently conjugated with HA, and the created HA-modified SiO2@MBs (HA-SiO2@MBs) display binding specificity to HeLa cells (a human cervical carcinoma cell line) overexpressing CD44 receptors. After incubating the HA-SiO2@MBs with cancer cells for 1 h, the mixture of MBs and cells was drawn into a designed microfluidic channel with two inlets and outlets. Through the formation of lamellar flow, cells specifically bound with the HA-SiO2@MBs can be separated under an external magnetic field with a capture efficiency of up to 92.0%. The developed method is simple, fast, and promising for CTC separation and cancer diagnostics applications.

Highly Efficient I2 Sorption, CO2 Capture, and Catalytic Conversion by Introducing Nitrogen Donor Sites in a Microporous Co(II)-Based Metal-Organic Framework.

Recently, the development of porous absorbents for efficient CO2 and I2 capture has attracted considerable attention because of severe global climate change and environmental issues with the nuclear energy. Hence, a unique porous metal-organic framework (MOF), {[Co(L)]·DMF·2H2O}n (1, DMF = N,N-dimethylformamide) with uncoordinated N atoms was rationally constructed via using a heterofunctional 4,6-bis(4'-carboxyphenyl)pyrimidine (H2L) linker. Interestingly, 1 exhibits exceptional properties for I2 sorption, CO2 capture, and catalytic conversion. Particularly, I2 can be efficiently removed in both vapor and solution forms, and the adsorption amount can reach 676.25 and 345.28 mg g-1, respectively. Furthermore, complex 1 displays high adsorption capacity for CO2 (53.78 cm3 g-1, 273 K). Consequently, 1 is expected to be a promising and practical material for environmental purification due to its excellent adsorption properties.

Kim-1 Targeted Extracellular Vesicles: A New Therapeutic Platform for RNAi to Treat AKI.

BACKGROUND: AKI is a significant public health problem with high morbidity and mortality. Unfortunately, no definitive treatment is available for AKI. RNA interference (RNAi) provides a new and potent method for gene therapy to tackle this issue. METHODS: We engineered red blood cell-derived extracellular vesicles (REVs) with targeting peptides and therapeutic siRNAs to treat experimental AKI in a mouse model after renal ischemia/reperfusion (I/R) injury and unilateral ureteral obstruction (UUO). Phage display identified peptides that bind to the kidney injury molecule-1 (Kim-1). RNA-sequencing (RNA-seq) characterized the transcriptome of ischemic kidney to explore potential therapeutic targets. RESULTS: REVs targeted with Kim-1-binding LTH peptide (REVLTH) efficiently homed to and accumulated at the injured tubules in kidney after I/R injury. We identified transcription factors P65 and Snai1 that drive inflammation and fibrosis as potential therapeutic targets. Taking advantage of the established REVLTH, siRNAs targeting P65 and Snai1 were efficiently delivered to ischemic kidney and consequently blocked the expression of P-p65 and Snai1 in tubules. Moreover, dual suppression of P65 and Snai1 significantly improved I/R- and UUO-induced kidney injury by alleviating tubulointerstitial inflammation and fibrosis, and potently abrogated the transition to CKD. CONCLUSIONS: A red blood cell-derived extracellular vesicle platform targeted Kim-1 in acutely injured mouse kidney and delivered siRNAs for transcription factors P65 and Snai1, alleviating inflammation and fibrosis in the tubules.

Construct validity and psychometric properties of the Chinese version of the City Birth Trauma Scale.

BACKGROUND: Currently, most postpartum posttraumatic stress disorder (PTSD) screening scales used in China are general PTSD scales which are not compiled specifically for pregnant women and thus cannot reflect the unique needs of this population. This study aimed to translate the City Birth Trauma Scale (City BiTS) into Chinese and validate its psychometric characteristics in Chinese postpartum women. METHODS: After translation, back-translation, and expert discussion, 596 mothers at 1 to 12 months postpartum filled out the questionnaires through the Internet. The reliability and validity of the translated questionnaire were tested. RESULTS: The Cronbach's α coefficient of the Chinese version of City BiTS (City BiTS-C) was 0.889, the test-retest reliability was 0.86, and the content validity was 0.93. Exploratory factor analysis extracted two factors accounted for 63.148% of the variance. The City BiTS-C had appropriate construct validity in the Chinese culture (root mean square error of approximation [RMSEA] = 0.048, <0.05; χ2 /df = 2.666, <3). The values of the incremental fit index (IFI) and the Tucker-Lewis coefficient (TLI) were 0.990 and 0.976, which identified that the model was a good fit for the data. The values of the comparative fit index (CFI) and the normed fit index (NFI) were 0.890 and 0.873, respectively. CONCLUSIONS: The City BiTS-C is a reliable and valid measure to screening and diagnosis the postpartum PTSD among new mothers who gave birth in the past year in mainland China. IMPLICATIONS: The City BiTS-C is a short, reliable, and valid instrument that measures the symptoms of postpartum PTSD, and it is recommend for clinical screening.

Cooling Kinetic Characteristics of Temperature Difference between Cadaver Temperature and Ambient Temperature.

OBJECTIVES: To study the cooling reaction kinetic characteristics of the temperature difference between cadaver temperature and ambient temperature (hereinafter referred to as "cadaver temperature difference") according to the reaction kinetics method. METHODS: Thirty rabbits were randomly divided into 5 groups with 6 rabbits in each group. The rabbits were injected with 10% potassium chloride solution intravenously. After death, the rabbits were placed at 5 ℃, 10 ℃, 15 ℃, 20 ℃ and 25 ℃ environment condition, respectively, and the rectal temperature was measured every minute for 20 hours. The measured cadaver temperature was subtracted from ambient temperature, and the cadaver temperature difference data was calculated using the reaction kinetics formula. The linear regression equation was fitted for analysis, and the experimental results were applied to the temperature difference data of human body after death for verification. RESULTS: Under different environmental conditions, the linear coefficient determination of temperature difference -ln(C/C0) in rabbits was 0.99, showing a good linear relationship with time t. The application of human body temperature data after death was consistent with the results of animal experiments. CONCLUSIONS: Under stable conditions, the temperature difference cooling process after death in rabbits is a first-order kinetic response. The method can also be used to study the temperature difference in human body after death.

Silver-Templated γ-Keggin Alkyltin-Oxo Cluster: Electronic Structure and Optical Limiting Effect.

As one of the most representative polyoxometalate (POM) structures, Keggin clusters have attracted considerable attention. Nevertheless, the noble-metal-templated Keggin structure has not been reported to date. In this work, for the first time, a Ag atom was successfully incorporated to template the formation of a γ-Keggin alkytin-oxo cluster. Moreover, the central Ag atom has brought a significant heavy atom effect, showing the important influence on the electronic structure and optical properties. Theoretical calculations demonstrate that the Ag atom affects the frontier molecular orbitals and excited states of the AgSn12 cluster, and also the process of electron transfer. The solid structure of the AgSn12 cluster exhibits a significant third-order nonlinear optical (NLO) response, and an excellent optical limiting effect has been experimentally verified. The success of this work opens the way for the construction and optical properties modulation of noble metal templated Keggin structures.

HIF-1α is transcriptionally regulated by NF-κB in acute kidney injury.

Oxygen homeostasis disturbances play a critical role in the pathogenesis of acute kidney injury (AKI). The transcription factor hypoxia-inducible factor-1 (HIF-1) is a master regulator of adaptive responses to hypoxia. Aside from posttranslational hydroxylation, the mechanism of HIF-1 regulation in AKI remains largely unclear. In this study, the mechanism of HIF-α regulation in AKI was investigated. We found that tubular HIF-1α expression significantly increased at the transcriptional level in ischemia-reperfusion-, unilateral ureteral obstruction-, and sepsis-induced AKI models, which was closely associated with macrophage-dependent inflammation. Meanwhile, NF-κB, which plays a central role in the inflammation response, was involved in the increasing expression of HIF-1α in AKI, as evidenced by pharmacological modulation (NF-κB inhibitor BAY11-7082). Mechanistically, NF-κB directly bound to the HIF-1α promoter and enhanced its transcription, which occurred not only under hypoxic conditions but also under normoxic conditions. Moreover, the induced HIF-1α by inflammation protected against tubular injury in AKI. Thus, our findings not only provide novel insights into HIF-1 regulation in AKI but also offer to understand the pathophysiology of kidney diseases.NEW & NOTEWORTHY Here, the mechanism of hypoxia-inducible factor-α (HIF-α) regulation in acute kidney injury (AKI) was investigated. We found that tubular HIF-1α expression significantly increased at the transcriptional level, which was closely associated with macrophage-dependent inflammation. Meanwhile, NF-κB was involved in the increasing expression of HIF-1α in AKI. Mechanistically, NF-κB directly bound to the HIF-1α promoter and enhanced its transcription. Our findings not only provide novel insights into HIF-1 regulation in AKI but also offer to understand the pathophysiology of kidney diseases.