Rab34 plays a critical role as a bidirectional regulator of osteoclastogenesis.

Accumulating evidence suggests that Rab GTPases representing the largest branch of Ras superfamily have recently emerged as the core factors for the regulation of osteoclastogenesis through modulating vesicular transport amongst specific subcellular compartments. Among these, Rab34 GTPase has been identified to be important for the post-Golgi secretory pathway and for phagocytosis; nevertheless, its specific role in osteoclastogenesis has been completely obscure. Here, upon the in vitro model of osteoclast formation derived from murine macrophages like RAW-D cells or bone marrow-derived macrophages, we reveal that Rab34 regulates osteoclastogenesis bidirectionally. More specifically, Rab34 serves as a negative regulator of osteoclast differentiation by promoting the lysosome-induced proteolysis of two osteoclastogenic surface receptors, c-fms and RANK, via the axis of early endosomes-late endosomes-lysosomes, leading to alleviate the transcriptional activity of two of the master regulator of osteoclast differentiation, c-fos and NFATc-1, eventually attenuating osteoclast differentiation and bone resorption. Besides, Rab34 plays a crucial role in modulating the secretory network of lysosome-related proteases including matrix metalloprotease 9 and Cathepsin K across the ruffled borders of osteoclasts, contributing to the regulation of bone resorption.

Machine learning model for predicting acute kidney injury progression in critically ill patients.

BACKGROUND: Acute kidney injury (AKI) is a serve and harmful syndrome in the intensive care unit. Comparing to the patients with AKI stage 1/2, the patients with AKI stage 3 have higher in-hospital mortality and risk of progression to chronic kidney disease. The purpose of this study is to develop a prediction model that predict whether patients with AKI stage 1/2 will progress to AKI stage 3. METHODS: Patients with AKI stage 1/2, when they were first diagnosed with AKI in the Medical Information Mart for Intensive Care, were included. We used the Logistic regression and machine learning extreme gradient boosting (XGBoost) to build two models which can predict patients who will progress to AKI stage 3. Established models were evaluated by cross-validation, receiver operating characteristic curve, and precision-recall curves. RESULTS: We included 25,711 patients, of whom 2130 (8.3%) progressed to AKI stage 3. Creatinine, multiple organ failure syndromes were the most important in AKI progression prediction. The XGBoost model has a better performance than the Logistic regression model on predicting AKI stage 3 progression. Thus, we build a software based on our data which can predict AKI progression in real time. CONCLUSIONS: The XGboost model can better identify patients with AKI progression than Logistic regression model. Machine learning techniques may improve predictive modeling in medical research.

The Inhibitory Role of Rab11b in Osteoclastogenesis through Triggering Lysosome-Induced Degradation of c-Fms and RANK Surface Receptors.

Rab11b, abundantly enriched in endocytic recycling compartments, is required for the establishment of the machinery of vesicle trafficking. Yet, no report has so far characterized the biological function of Rab11b in osteoclastogenesis. Using in vitro model of osteoclasts differentiated from murine macrophages like RAW-D cells or bone marrow-derived macrophages, we elucidated that Rab11b served as an inhibitory regulator of osteoclast differentiation sequentially via (i) abolishing surface abundance of RANK and c-Fms receptors; and (ii) attenuating nuclear factor of activated T-cells c1 (NFATc-1) upstream signaling cascades, following RANKL stimulation. Rab11b was localized in early and late endosomes, Golgi complex, and endoplasmic reticulum; moreover, its overexpression enlarged early and late endosomes. Upon inhibition of lysosomal function by a specific blocker, chloroquine (CLQ), we comprehensively clarified a novel function of lysosomes on mediating proteolytic degradation of c-Fms and RANK surface receptors, drastically ameliorated by Rab11b overexpression in RAW-D cell-derived osteoclasts. These findings highlight the key role of Rab11b as an inhibitor of osteoclastogenesis by directing the transport of c-Fms and RANK surface receptors to lysosomes for degradation via the axis of early endosomes-late endosomes-lysosomes, thereby contributing towards the systemic equilibrium of the bone resorption phase.

MicroRNA-132-3p represses Smad5 in MC3T3-E1 osteoblastic cells under cyclic tensile stress.

MicroRNAs (miRNAs) regulate osteogenic differentiation of bone cells, which has applications in orthodontics. Here we evaluated the miRNA expression profile of MC3T3-E1 osteoblasts under cyclic tensile stress with chip technology and found that miR-132-3p was up-regulated by 12% cyclic tensile stress. Alkaline phosphatase activity and osteocalcin expression in MC3T3-E1 cells were decreased under these conditions. Smad2 and Smad5 were identified as potential target genes of miR-132-3p. Native and phosphorylated Smad2 and Smad5 expression was negatively correlated with miR-132-3p levels in the cells under cyclic stretch; however, only Smad5 protein level was reduced upon miR-132-3p overexpression. The luciferase reporter assay confirmed a direct interaction between miR-132-3p and Smad5. Thus, miR-132-3p maybe regulates osteoblast differentiation via Smad5 in response to cyclic tensile stress.

[Effect of Xinfeng Capsule on Pulmonary Function, Thi/Th2 Cells, and Regulatory T Cells of Adjuvant Arthritis Rats].

Objective To observe the effects of Xinfeng Capsule (XFC) at different doses on lung function, Thl/Th2 cells, regulatory T cells (Treg) in adjuvant arthritis (AA) rats. Methods Totally 84 rats were randomly divided into 5 groups, i.e., the normal control group (NC) , the model group (M) , the methotrexate (MTX) group, the Tripterygium Glycosides Table (TGT) group, the low dose XFC (XFC- L) group, the medium dose XFC (XFC-M) group, the high dose XFC (XFC-H) group, 12 in each group. Freund's complete adjuvant (FCA; 0. 1 mL) was intradermally injected to all rats except those in the NC group from right rear paw to induce inflammation. Medication was started from the 19th day after inflam- mation. Normal saline was administered to rats in the NC group and the M group. Rats in the rest groups were correspondingly administered with MTX, TGT, XFC, respectively. Changes of each index were ob- served in all groups. Results (1) Compared with the NC group, rat paw swelling degree (E) , arthritis index (AI) , lung index (LI) , average expiratory flow in 1 second (FEV1/FVC%) , alveolitis integral, TNF- α, Th1/Th2 cells, transforming growth factor-ß1 ( TGF-ß1 ) expression significantly increased in the M group (P <0. 01) ; forced vital capacity (FVC) , peak expiratory flow 25% of vital capacity (FEF25), peak expiratory flow 50% of vital capacity (FEF50), peak expiratory flow 75% of vital capacity (FEF75), the maximum mid-expiratory flow (MMF) , peak expiratory flow (PEF) , CD4 ⁺Treg, CD4⁺CD25 ⁺Treg, IL-10, and Foxp3 expression significantly decreased in the M group (P <0. 01). (2) Compared with the M group, body weight, FVC, FEF25, FEF50, FEF75, MMF, PEF, IL-10, Treg, and Foxp3 expression increased in all treatment groups; E, Al, LI, FEV1/FVC%, TNF-α, Th1/Th2 cells, and TGF-ß1 expression decreased in all treatment groups (P <0. 05, P <0. 01). (3) Compared with the XFC-M group, LI, alveolitis integral, TNF- α, Th1/Th2 cells, and TGF-ß1 increased; FVC, FEF25, FEF50, FEF75, IL-10, CD4⁺Treg, CD4⁺CD25⁺ Treg, and Foxp3 decreased in other treatment groups (P <0. 05, P <0. 01). Conclusions AA rats had local swollen paws and decreased lung function. XFC could significantly improve paw swelling and Al of AA rats, and improve lung function. It could reduce inflammatory reaction and immune complexes on tis- sue and organ damage, improve joint and pulmonary symptoms possibly through promoting expressions of IL-10, CD4⁺Treg, CD4⁺CD25⁺Treg, and Foxp3, and inhibiting TNF-α,Th1/Th2 cells, and TGF-ß1 ex- pression.

Correlation between plasma renalase level and coronary artery disease.

OBJECTIVE: To explore the correlation between the plasma renalase level of coronary artery disease (CAD) patients and the degree of coronary artery stenosis. METHODS: A total of 180 patients who received coronary angiography in our hospitals from August 2013 to October 2013 were selected as the CAD group, of which 164 were finally diagnosed as CAD. Another 140 healthy subjects were selected as the control group. The plasma renalase levels of the two groups were detected by ELISA to analyze CA-induced changes and to clarify the correlations with the number of branches with coronary artery stenosis and Syntax scores. RESULTS: The plasma renalase level of the CAD group was significantly lower than that of the control group (P<0.05). The plasma renalase levels of the multi-branch and two-branch stenosis subgroups were significantly lower than that of the subgroup with normal coronary angiography outcomes (P<0.05), while the levels of the single-branch stenosis and normal subgroups were similar (P>0.05). Besides, the plasma renalase level of the low-risk subgroup was significantly higher than those of the medium-risk and high-risk subgroups (P<0.05), and the level of the medium-risk subgroup was significantly higher than that of the high-risk subgroup (P<0.05). Multivariate Logistic regression analysis showed that renalase level was the risk factor of CAD (OR=1.12, 95%CI: 1.03-3.34). CONCLUSION: Plasma renalase level was correlated with CAD, the changes of which may reflect the degree of coronary artery stenosis. Therefore, plasma renalase level can be used to indicate the progression of CAD.

Breakdown of Ohm's Law in Molecular Junctions with Electrodes of Single-Layer Graphene.

For sufficiently low biases, Ohm's law, the cornerstone of electricity, stating that current I and voltage V are proportional, is satisfied at low biases for all known systems ranging from macroscopic conductors to nanojunctions. In this study, we predict theoretically and demonstrate experimentally that in single-molecule junctions fabricated with single-layer graphene as electrodes the current at low V scales as the cube of V, thereby invalidating Ohm's law. The absence of the ohmic regime is a direct consequence of the unique band structure of the single-layer graphene, whose vanishing density of states at the Dirac points precludes electron transfer from and to the electrodes at low biases.

Protection by face masks against influenza A(H1N1)pdm09 virus on trans-Pacific passenger aircraft, 2009.

In response to several influenza A(H1N1)pdm09 infections that developed in passengers after they traveled on the same 2 flights from New York, New York, USA, to Hong Kong, China, to Fuzhou, China, we assessed transmission of influenza A(H1N1)pdm09 virus on these flights. We defined a case of infection as onset of fever and respiratory symptoms and detection of virus by PCR in a passenger or crew member of either flight. Illness developed only in passengers who traveled on the New York to Hong Kong flight. We compared exposures of 9 case-passengers with those of 32 asymptomatic control-passengers. None of the 9 case-passengers, compared with 47% (15/32) of control-passengers, wore a face mask for the entire flight (odds ratio 0, 95% CI 0-0.71). The source case-passenger was not identified. Wearing a face mask was a protective factor against influenza infection. We recommend a more comprehensive intervention study to accurately estimate this effect.

The association between procalcitonin and acute kidney injury in patients stung by wasps.

Introduction: The aim of this study was to investigate the status of serum procalcitonin (PCT) in patients stung by wasps and evaluate the association between PCT levels and acute kidney injury (AKI). Methods: Patients stung by wasps admitted to two tertiary hospitals between January 2017 and December 2020 were screened for enrollment. We evaluated serum PCT levels on admission in patients stung by wasps. The patients were divided into an AKI group and a non-AKI group. A logistic regression model was used to analyze the association between PCT status and AKI. The performance of PCT concentrations in predicting the occurrence of AKI was evaluated by the area under the receiver operating characteristic curve (AUROC). Results: A total of 138 patients were enrolled, and 66 patients suffered AKI. PCT levels were elevated in 78.99% of patients stung by wasps. Nearly half of the patients (47.83%) developed AKI. PCT levels were correlated with creatinine levels on admission (r = 0.787, 95% CI: 0.713-0.844). PCT levels in patients with AKI were higher than those in patients without AKI (p < 0.001). After adjustment for covariates, PCT levels on admission were independently associated with AKI (OR: 1.575, 95% CI: 1.071-2.317, p = 0.021). The AUROC of PCT levels on admission was 0.837 (95% CI, 0.771-0.902, p < 0.001). A PCT level of 0.57 µg/L was the cutoff for maximizing the Youden index; the specificity was 79.45%, and the sensitivity was 73.43%. Conclusion: Serum PCT levels may be a potential biomarker of AKI in patients stung by wasps.

Transmission dynamics, border entry screening, and school holidays during the 2009 influenza A (H1N1) pandemic, China.

Pandemic influenza A (H1N1) 2009 virus spread rapidly around the world in 2009. We used multiple data sources from surveillance systems and specific investigations to characterize the transmission patterns of this virus in China during May-November 2009 and analyze the effectiveness of border entry screening and holiday-related school closures on transmission. In China, age distribution and transmission dynamic characteristics were similar to those in Northern Hemisphere temperate countries. The epidemic was focused in children, with an effective reproduction number of ≈1.2-1.3. The 8 days of national holidays in October reduced the effective reproduction number by 37% (95% credible interval 28%-45%) and increased underreporting by ≈20%-30%. Border entry screening detected at most 37% of international travel-related cases, with most (89%) persons identified as having fever at time of entry. These findings suggest that border entry screening was unlikely to have delayed spread in China by >4 days.

[Value of procalcitonin as a potential biomarker in predicting acute kidney injury in patients with bee stings].

OBJECTIVE: To investigate the predictive value of procalcitonin (PCT) in the development of acute kidney injury (AKI) in patients after bee stings. METHODS: A total of 105 bee stings patients admitted to Mianyang Central Hospital from May 2019 to August 2021 were enrolled and were divided into AKI group (37 cases) and non-AKI group (68 cases) according to the occurrence of AKI. Baseline demographic information [gender, age, body mass index (BMI), sting season, sting site, number of stings, underlying disease, clinical manifestations, and inflammatory factor levels] were collected and compared between the two groups. Logistic regression model was used to analyze the risk factors associated with the occurrence of AKI in bee stings patients. Pearson model was used to analyze the correlation between PCT and other indicators; the receiver operator characteristic curve (ROC curve) were drawn to analyze the predictive value of each indicator on the occurrence of AKI in bee stings patients. RESULTS: There were significant differences in age, number of bee stings, and vomiting after admission between the two groups of patients. The levels of serum creatinine (SCr), PCT, interleukin-6 (IL-6) and hypersensitive C-reactive protein (hs-CRP) were significantly higher in the AKI group than those in the non-AKI patients [SCr (µmol/L): 122.36±32.45 vs. 76.74±28.52, PCT (µg/L): 1.42±1.05 vs. 0.34±0.21, IL-6 (ng/L): 277.52±120.25 vs. 112.14±73.34, hs-CRP (mg/L): 7.64±3.26 vs. 3.01±2.13, all P < 0.05]. Serum PCT levels were positively correlated with serum SCr, IL-6, and hs-CRP levels in patients with AKI after bee stings (r values of 0.486, 0.393, and 0.425, respectively; P = 0.002, 0.016, and 0.009, respectively). Multivariate Logistic analysis showed that age, SCr, PCT, IL-6, and hs-CRP were independent risk factors for AKI in patients with bee stings. The ROC curve analysis showed that the area under the ROC curve (AUC) of age, SCr, PCT, IL-6 and hs-CRP for predicting AKI in patients with bee stings were 0.622 [95% confidence interval (95%CI) was 0.516 to 0.727], 0.722 (95%CI was 0.601 to 0.843), 0.869 (95%CI was 0.781 to 0.958), 0.739 (95%CI was 0.627 to 0.851) and 0.799 (95%CI was 0.700 to 0.900), respectively. The best cut-off value of PCT was 0.742 µg/L, the sensitivity was 75.70% and the specificity was 90.50%. CONCLUSIONS: The serum PCT level was significantly elevated in patients with AKI after bee stings, which is an independent risk factor for AKI after bee stings. Serum PCT level has better predictive efficacy for AKI after bee stings and can be used as a valid biomarker for clinical prediction.

Preparation and Application of a Novel Slow-Releasing with Core-Shell Deicer in Asphalt Mixtures.

The massive application of chloride salts has a direct effect on the corrosion of structures and vehicles and decreases durability as well as road pavement damage. A novel slow-release deicer with a core-shell structure was prepared to reduce the salts' impacts, subsequently characterized by scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS), differential scanning calorimetry (DSC), and thermogravimetric analysis (TG). The conductivity evaluation, moisture absorption, and the snow or ice melting performance of the deicer were also tested. The core-shell deicer with different replacement rates was used to prepare the deicing asphalt mixture based on the equivalent volume replacement method. In this study, the high- and low-temperature performance, moisture damage resistance, and snow or ice melting capacity of mixtures were evaluated in the laboratory. The results show that the low-temperature and moisture stability performances decreased, and high-temperature performance improved, as the content of the core-shell deicer was increased. It is confirmed that the replacement rate of the deicer filler should be lower than 75% to meet the specification requirements. The prepared deicing asphalt mixture has good snow and ice melting performance and can reduce the bonding strength between ice and pavement surface. Durability and cost-benefit analysis are expected in further investigations.

Characteristics, influence factors, and health risk assessment of volatile organic compounds through one year of high-resolution measurement at a refinery.

From January 2020 to December 2020, high-resolution data of volatile organic compound (VOC) concentrations were monitored by online instruments at a petroleum refinery. The measurement results showed that the external contaminants, meteorological conditions and photochemical reactions had a great influence on the VOC data measured in the petroleum refineries. Some significant differences were observed in the emission composition of different refineries, while propene (34.2%), propane (10.2%), n-butane (5.6%), i-pentane (5.0%) were the dominant species emitted from the refinery in this study. The correlations between compounds with similar atmospheric lifetimes were strong (R2 > 0.9), which indicated that the diagnostic ratios of these compounds could be used as indicators to identify the refinery emission source. Chronic health effects of non-carcinogenic risk results showed that acrolein had the highest non-carcinogenic risk and other compound-specific health risks may be of less concern in the refining area. Halogenates and aromatics accounted for 97.4% of the total carcinogenic risk values, while 1,2-dibromoethane, chloromethane, benzene, trichloromethane, 1,2-dichloroethane contributed approximately 80% of the total carcinogenic risk assessment values. This research has recorded valuable data about the VOC emission characteristics from the perspective of the high-resolution monitoring of the petroleum refinery. The results of this work will provide a reference to accurately quantify and identify the emission of petroleum refineries and further throw some light on effective VOC abatement strategies.

Effect of Metakaolin on the Microstructural and Chloride Ion Transport Properties of Concrete in Ocean Wave Splashing Zones.

In order to address the problem of the durability deficiency of concrete in wave splash zones in a harsh marine environment, this paper investigates the effects of coupled carbonation, sulfate, and chloride salts on the strength, capillary water absorption, and ion migration properties of cement concrete incorporated with metakaolin, and characterizes the pore structural changes with the mercury-pressure method and AC impedance technique. The results show that, compared with a single chloride salt environment, the improvement in mortar strength and impermeability with carbonation coupling is almost positively correlated with the calcium content in the specimen, and renders its pore structure more refined and denser. In contrast, the presence of sulfate reduces mortar strength and increases the ion migration coefficient. When the three factors of sulfate, carbonation, and chloride salt were coupled, damage to the strength and pore structure of the specimens was the most significant, but the specimen incorporated with 30% metakaolin had its strength improved compared with the blank group specimen; from the perspective of pore structural parameters and transport coefficient, the microstructure was denser, and the impermeability was significantly improved.

Performance of the PRISM I, PIM2, PELOD-2 and PRISM IV scoring systems in western China: a multicenter prospective study.

BACKGROUND: The aim of this study was to evaluate the performance of the four scoring tools in predicting mortality in pediatric intensive care units (PICUs) in western China. METHODS: This was a multicenter, prospective, cohort study conducted in six PICUs in western China. The performances of the scoring systems were evaluated based on both discrimination and calibration. Discrimination was assessed by calculating the area under the receiver operating characteristic curve (AUC) for each model. Calibration was measured across defined groups based on mortality risk using the Hosmer-Lemeshow goodness-of-fit test. RESULTS: A total of 2034 patients were included in this study, of whom 127 (6.2%) died. For the entire cohort, AUCs for Pediatric Risk of Mortality Score (PRISM) I, Pediatric Index of Mortality 2 (PIM2), Pediatric Logistic Organ Dysfunction Score-2 (PELOD-2) and PRISM IV were 0.88 [95% confidence interval (CI) 0.85-0.92], 0.84 (95% CI 0.80-0.88), 0.80 (95% CI 0.75-0.85), and 0.91 (95% CI 0.88-0.94), respectively. The Hosmer-Lemeshow goodness-of-fit Chi-square value was 12.71 (P = 0.12) for PRISM I, 4.70 (P = 0.79) for PIM2, 205.98 (P < 0.001) for PELOD-2, and 7.50 (P = 0.48) for PRISM IV [degree of freedom (df) = 8]. The standardized mortality ratios obtained with the PRISM I, PIM2, PELOD-2, and PRISM IV models were 0.87 (95% CI, 0.75-1.01), 0.97 (95% CI, 0.85-1.12), 1.74 (95% CI, 1.58-1.92), and 1.05 (95% CI, 0.92-1.21), respectively. CONCLUSIONS: PRISM IV performed best and can be used as a prediction tool in PICUs in Western China. However, PRISM IV needs to be further validated in NICUs.

Risk factors for severe illness with 2009 pandemic influenza A (H1N1) virus infection in China.

BACKGROUND: Data on risk factors for severe outcomes from 2009 pandemic influenza A (H1N1) virus infection are limited outside of developed countries. METHODS: We reviewed medical charts to collect data from patients hospitalized with laboratory-confirmed 2009 H1N1 infection who were identified across China during the period from September 2009 through February 2010, and we analyzed potential risk factors associated with severe illness (defined as illness requiring intensive care unit admission or resulting in death). RESULTS: Among 9966 case patients, the prevalence of chronic medical conditions (33% vs 14%), pregnancy (15% vs 7%), or obesity (19% vs 14%) was significantly higher in those patients with severe illness than it was in those with less severe disease. In multivariable analyses, among nonpregnant case patients aged ≥ 2 years, having a chronic medical condition significantly increased the risk of severe outcome among all age groups, and obesity was a risk factor among those <60 years of age. The risk of severe illness among pregnant case patients was significantly higher for those in the second and third trimesters. The risk of severe illness was increased when oseltamivir treatment was initiated ≥ 5 days after illness onset (odds ratio, 1.42; 95% confidence interval, 1.20-1.67). For persons <60 years of age, the prevalence of obesity among case patients with severe illness was significantly greater than it was among those without severe illness or among the general population. CONCLUSIONS: Risk factors for severe 2009 H1N1 illness in China were similar to those observed in developed countries, but there was a lower prevalence of chronic medical conditions and a lower prevalence of obesity. Obesity was a risk factor among case patients < 60 years of age. Early initiation of oseltamivir treatment was most beneficial, and there was an increased risk of severe disease when treatment was started ≥ 5 days after illness onset.

[Quality standard of stewed rhizoma polygonati with yellow wine].

OBJECTIVE: To improve the quality standard of stewed Rhizoma Polygonati with yellow wine. METHODS: On the basis of Chinese Pharmacopoeia 2010, some items were added, which included assay of reducing sugars, water-soluble extracts, acid insoluble ash content and 5-hydroxymethylfurfural. RESULTS: Reducing sugars was no less than 34.0%, water-soluble extracts no less than 19.0%, acid insoluble ash content no more than 0.2%, 5-hydroxymethylfurfural no more than 0.02%. CONCLUSION: The quality standard of stewed Rhizoma Polygonati with yellow wine is improved on the basis of Chinese Pharmacopoeia.

Meta-analysis of procalcitonin as a predictor for acute kidney injury.

BACKGROUND: Procalcitonin (PCT) was used for predicting the development of acute kidney injury (AKI) in several studies recently. We aimed to investigate the accuracy of PCT for predicting AKI in this study. METHODS: Studies that assessed the predictive performance of PCT for the development of AKI in adult patients were searched from Medline, Embase, and the Cochrane Library from inception to June 2020. We calculated the pooled sensitivities and specificities and the area under the summary receiver-operating characteristic (SROC) curves. I2 was used to test the heterogeneity and the potential heterogeneity was investigated by meta-regression. RESULTS: In total, 9 of 119 studies with 4852 patients were included, 1272 were diagnosed with AKI. In the overall analysis, the area under the SROC curve was 0.82 (95% CI, 0.79-0.85) and the pooled sensitivity and specificity were 0.76 (95% confidence interval [CI], 0.64-0.85) and 0.75 (95% CI, 0.61-0.86), respectively. In the subgroup analysis among septic patients, the pooled sensitivity and specificity were 0.59 (95% CI, 0.29-0.84) and 0.53 (95% CI, 0.31-0.74), and the area under the SROC was 0.57 (95% CI, 0.53-0.62). CONCLUSION: PCT may be a potential predictor for the development of AKI.

A novel role of HSP90 in regulating osteoclastogenesis by abrogating Rab11b-driven transport.

Heat shock protein 90 (HSP90) is a highly conserved molecular chaperone that plays a pivotal role in folding, activating and assembling a variety of client proteins. In addition, HSP90 has recently emerged as a crucial regulator of vesicular transport of cellular proteins. In our previous study, we revealed Rab11b negatively regulated osteoclastogenesis by promoting the lysosomal proteolysis of c-fms and RANK surface receptors via the axis of early endosome-late endosome-lysosomes. In this study, using an in vitro model of osteoclasts differentiated from murine macrophage-like RAW-D cells, we revealed that Rab11b interacted with both HSP90 isoforms, HSP90 alpha (HSP90α) and HSP90 beta (HSP90ß), suggesting that Rab11b is an HSP90 client. Using at specific blocker for HSP90 ATPase activity, 17-allylamino-demethoxygeldanamycin (17-AAG), we found that the HSP90 ATPase domain is indispensable for maintaining the interaction between HSP90 and Rab11b in osteoclasts. Nonetheless, its ATPase activity is not required for regulating the turnover of endogenous Rab11b. Interestingly, blocking the interaction between HSP90 and Rab11b by either HSP90-targeting small interfering RNA (siHSP90) or 17-AAG abrogated the inhibitory effects of Rab11b on osteoclastogenesis by suppressing the Rab11b-mediated transport of c-fms and RANK surface receptors to lysosomes via the axis of early endosome-late endosome-lysosomes, alleviating the Rab11b-mediated proteolysis of these surface receptors in osteoclasts. Based on our observations, we propose a HSP90/Rab11b-mediated regulatory mechanism for osteoclastogenesis by directly modulating the c-fms and RANK surface receptors in osteoclasts, thereby contributing to the maintenance of bone homeostasis.

Nickel-Catalyzed Reductive Aryl Thiocarbonylation of Alkene via Thioester Group Transfer Strategy.

Herein reported is a nickel-catalyzed reductive aryl thiocarbonylation of alkene via thioester group transfer strategy by using simple and readily available thioesters. In contrast to traditional activation of weaker C(acyl)-S bond, the C(acyl)-C bond of thioester was selectively cleaved to enable this reaction under mild conditions. Furthermore, this approach features operational simplicity and broad substrate scope, providing a complementary and practical route for thioester synthesis without requiring toxic thiol or CO gas.