Impdh2 deficiency suppresses osteoclastogenesis through mitochondrial oxidative phosphorylation and alleviates ovariectomy-induced osteoporosis.

Abnormalities in osteoclastic generation or activity disrupt bone homeostasis and are highly involved in many pathologic bone-related diseases, including rheumatoid arthritis, osteopetrosis, and osteoporosis. Control of osteoclast-mediated bone resorption is crucial for treating these bone diseases. However, the mechanisms of control of osteoclastogenesis are incompletely understood. In this study, we identified that inosine 5'-monophosphate dehydrogenase type II (Impdh2) positively regulates bone resorption. By histomorphometric analysis, Impdh2 deletion in mouse myeloid lineage cells (Impdh2LysM-/- mice) showed a high bone mass due to the reduced osteoclast number. qPCR and western blotting results demonstrated that the expression of osteoclast marker genes, including Nfatc1, Ctsk, Calcr, Acp5, Dcstamp, and Atp6v0d2, was significantly decreased in the Impdh2LysM-/- mice. Furthermore, the Impdh inhibitor MPA treatment inhibited osteoclast differentiation and induced Impdh2-cytoophidia formation. The ability of osteoclast differentiation was recovered after MPA deprivation. Interestingly, genome-wide analysis revealed that the osteoclastic mitochondrial biogenesis and functions, such as oxidative phosphorylation, were impaired in the Impdh2LysM-/- mice. Moreover, the deletion of Impdh2 alleviated ovariectomy-induced bone loss. In conclusion, our findings revealed a previously unrecognized function of Impdh2, suggesting that Impdh2-mediated mechanisms represent therapeutic targets for osteolytic diseases.

Clinical risk factors and cancer risk of thyroid imaging reporting and data system category 4 A thyroid nodules.

PURPOSE: Beyond the Thyroid Imaging Reporting and Data System (TIRADS) classification of thyroid nodules, additional factors must be weighed in the decision to perform fine needle aspiration (FNA). In this study, we aimed to identify risk factors for malignancy in patients with ultrasound-classified Chinese-TIRADS (C-TIRADS) 4 A nodules. METHODS: Patients who underwent thyroid FNA at our institution between May 2021 and September 2022 were enrolled. We collected demographic data, including age, sex, previous radiation exposure, and family history. An in-person questionnaire was used to collect lifestyle data, such as smoking habits and alcohol consumption. Body mass index (BMI) was calculated. The serum levels of thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) were measured. Prior to FNA, ultrasonic inspection reports were reviewed. The cytologic diagnoses for FNA of thyroid nodules followed the Bethesda System for Reporting Thyroid Cytopathology (2017). RESULTS: Among the 252 C-TIRADS 4 A nodules, 103 were malignant. Compared to those in the benign group, the patients in the malignant group had a younger age (42.2 ± 13.6 vs. 51.5 ± 14.0 years, P < 0.001). Logistic regression showed that advanced age was associated with a lower risk of malignancy in C-TIRADS 4 A nodules (OR = 0.95, 95% CI 0.93 ~ 0.97, P < 0.001). We demonstrated a decreased risk of malignancy in patients with 48.5 years or older. CONCLUSION: Advanced age was associated with a decreased risk of malignancy in patients with C-TIRADS 4 A nodules. This study indicated that in addition to sonographic characteristics, patient age should be considered when assessing the risk of malignancy.

A p38 MAP kinase inhibitor suppresses osteoclastogenesis and alleviates ovariectomy-induced bone loss through the inhibition of bone turnover.

Inhibition of excessive osteoclastic activity is an efficient therapeutic strategy for many bone diseases induced by increased bone resorption, such as osteoporosis. BMS-582949, a clinical p38α inhibitor, is a promising drug in Phase II studies for treating rheumatoid arthritis. However, its function on bone resorption is largely unknown. In this study, we find that BMS-582949 represses RANKL-induced osteoclast differentiation in a dose-dependent manner. Moreover, BMS-582949 inhibits osteoclastic F-actin ring formation and osteoclast-specific gene expression. Mechanically, BMS-582949 treatment attenuates RANKL-mediated osteoclastogenesis through mitogen-activated protein kinases (MAPKs) and protein kinase B (AKT) signaling pathways without disturbing nuclear factor-κB (NF-κB) signaling. Interestingly, BMS-582949 impairs osteoclastic mitochondrial biogenesis and functions, such as oxidative phosphorylation (OXPHOS). Furthermore, BMS-582949 administration prevents bone loss in ovariectomized mouse mode by inhibiting both bone resorption and bone formation in vivo. Taken together, these findings indicate that BMS-582949 may be a potential and effective drug for the therapy of osteolytic diseases.

The Tao Hong Si Wu Decoction ameliorates diabetes-associated cognitive dysfunction by inhibiting the formation of amyloid plaques.

OBJECTIVES: The herbs in Tao Hong Si Wu Decoction (THSWD) are beneficial in the treatment of cognitive impairment. However, the underlying mechanisms of THSWD in treating diabetes-associated cognitive dysfunction (DACD) are not entirely explored. This study is aimed to investigate the therapeutic effects of THSWD in DACD model rats and the underlying mechanism. METHODS: Ultra-high-phase liquid chromatography was employed to identify the main compounds contained in the THSWD extract. DACD rat model was induced by feeding with a high-sugar and high-fat diet and injecting streptozotocin (35 mg/kg). DACD rats were gavaged with THSWD for 1 week. The learning and memory abilities of the rats were measured by using the Morris water maze. Western blotting was used to detect the changes in DACD rat targets. Statistical methods were used to evaluate the correlation between proteins. RESULTS: The results show that THSWD effectively reduced the escape latency, hippocampal neuron damage, glycosylated hemoglobin, type A1C, and blood lipid levels in DACD rats. Furthermore, DACD rats showed significantly increased amyloid precursor protein, ß-secretase, Aß1-40 , Aß1-42 , Tau phosphorylation, and advanced glycation end products (AGEs) expression. However, THSWD treatment can reverse this phenomenon. CONCLUSIONS: THSWD can improve the learning and memory abilities of DACD rats by inhibiting the expression of AEGs-AGE receptors pathway, which provides an experimental basis for the clinical application of THSWD. In addition, the experiment combines pharmacological and statistical methods, which offers a new perspective for the study of Chinese herbal medicine.

Ultra-performance liquid chromatography-quadrupole time-of-flight mass combined with UNIFI to study the mechanism of Tao Hong Si Wu Decoction in the treatment of postpartum blood stasis.

Postpartum hemorrhage can lead to a variety of maternal complications. Tao Hong Si Wu Decoction (THSWD) is a traditional Chinese medicine used for treating gynecological diseases. However, the active ingredients of THSWD and its pharmacological mechanism of treatment for postpartum blood stasis still remained unclear. In this study, 201 components were identified in THSWD ethanol extract using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry, including 59 terpenoids and volatile oil, 61 Phenylpropanoids, 41 flavonoids, 22 alkaloids, and other 18 components. A total of 45 active compounds were identified in the blood and 33 active compounds were identified in the uterine. Taking the common components into the blood and into the uterus combined with network pharmacology. It was demonstrated that the active compounds can bind to the core target with good affinity through molecular docking. The results of this study will provide a reference for the quality control and pharmacodynamic material base research of THSWD.

Clinical characteristics and surgical management of facial infiltrating lipomatosis: a single center experience.

BACKGROUND: Facial infiltrating lipomatosis (FIL) is a rare condition characterized by congenital facial enlargement. Beyond its impact on physical appearance, FIL can also impair essential facial functions such as swallowing, chewing, vision, and breathing, imposing a substantial physiological and psychological burden. Currently, fewer than 80 cases of FIL have been reported, and the characteristics and management strategies for FIL remain unclear. METHODS: We reviewed the clinical, surgical, and radiological records of 39 FIL patients who were treated at our center. Of these, genetic testing was performed for 21 patients. RESULTS: Aberrant overgrowth involves subcutaneous fat, bones, muscles, glands, tongue, lips, and teeth. Epidermal nevi could be observed in the dermatomes innervated by the three branches of the trigeminal nerve, with the highest frequency seen in the dermatome of the mandibular branch. Four patients exhibited concurrent hemimegalencephaly (HMEG), with one case presenting HMEG on the opposite side of the FIL. Nineteen patients were confirmed to harbor the PIK3CA mutation. Thirty-three patients underwent surgical procedures, with a post resection recurrence rate of approximately 25%. CONCLUSIONS: A variety of maxillofacial structures may be involved in FIL. PIK3CA mutations are important pathogenic factors. Emerging targeted therapies could present an additional treatment avenue in the future. However, surgery currently remains the predominant treatment choice for FIL. The timing and modality of surgery should be individually customized, taking into account each patient's unique circumstances. Notably, there is a significant possibility of postoperative recurrence during childhood and adolescence, necessitating early strategic planning of disease management.

Histologic image-based ensemble model to identify myenteric plexitis and predict endoscopic postoperative recurrence in Crohn's disease: a multicentre, retrospective study.

BACKGROUND AND AIM: Myenteric plexitis is correlated with postoperative recurrence of Crohn's disease when relying on traditional statistical methods. However, comprehensive assessment of the myenteric plexus remains challenging. This study aimed to develop and validate a deep learning system to predict postoperative recurrence through automatic screening and identification of features of the muscular layer and myenteric plexus. METHODS: In this study, we retrospectively reviewed 205 patients who underwent bowel resection surgery from 2 hospitals. Patients were divided into a training cohort (n=108), an internal validation cohort (n=47) and an external validation cohort (n=50). A total of 190960 patches from 278 whole-slide images of surgical specimens were analysed using ResNet50, and 6144 features were extracted after transfer learning. We used five robust algorithms to construct classification models. The performances of the models were evaluated by the area under the receiver operating characteristic curve in three cohorts. RESULTS: The stacking model achieved satisfactory accuracy in predicting postoperative recurrence of CD in the training cohort (AUC: 0.980; 95% CI 0.960-0.999), internal validation cohort (AUC: 0.908; 95% CI 0.823-0.992), and external validation cohort (AUC: 0.868; 95% CI 0.761-0.975). The accuracy for identifying the severity of myenteric plexitis was 0.833, 0.745, and 0.694 in the training cohort, internal validation cohort and external validation cohort, respectively. CONCLUSIONS: Our work initially established an interpretable stacking model based on muscular layer and myenteric plexus features extracted from histologic images to identify the severity of myenteric plexitis and predict postoperative recurrence of CD.

Differentiation of geniculate ganglion venous malformation from schwannoma: dynamic T1-weighted imaging provides unique diagnostic value.

OBJECTIVE: To distinguish geniculate ganglion venous malformation (GGVM) from schwannoma (GGS) by using high-resolution CT (HRCT), routine MRI, and dynamic T1-weighted imaging (T1WI) characteristics. METHODS: Surgically confirmed GGVMs and GGSs between 2016 and 2021 were retrospectively included. Preoperative HRCT, routine MR, and dynamic T1WI were performed on all patients. Clinical data, imaging characteristics including lesion size, involvement of facial nerve (FN), signal intensity, enhancement pattern on dynamic T1WI, and bone destruction on HRCT were evaluated. Logistic regression model was developed to identify independent factors for GGVMs, and the diagnostic performance was accessed by receiving operative curve (ROC) analysis. Histological characteristics were explored for both GGVMs and GGSs. RESULTS: Twenty GGVMs and 23 GGSs with mean age of 31 were included. On dynamic T1WI, 18 GGVMs (18/20) showed "pattern A" enhancement (a progressive filling enhancement), while all 23 GGSs showed "pattern B" enhancement (a gradual whole-lesion enhancement) (p < 0.001). Thirteen GGVMs (13/20) showed the "honeycomb" sign whereas all GGS (23/23) showed extensive bone changes on HRCT (p < 0.001). Lesion size, involvement of FN segment, signal intensity on non-contrast T1WI and T2-weighted imaging (T2WI), and homogeneity on enhanced T1WI were obviously differed between two lesions (p < 0.001, p = 0.002, p < 0.001, p = 0.01, p = 0.02, respectively). Regression model showed the "honeycomb" sign and "pattern A" enhancement were independent risk factors. Histologically, GGVM was characterized by interwoven dilated and tortuous veins, while GGS was characterized by abundant spindle cells with dense arterioles or capillaries. CONCLUSIONS: The "honeycomb" sign on HRCT and "pattern A" enhancement on dynamic T1WI are the most promising imaging characteristics for differentiating GGVM from GGS. CLINICAL RELEVANCE STATEMENT: The characteristic sign and enhancement pattern on HRCT and dynamic T1-weighted imaging allow preoperative differentiation of geniculate ganglion venous malformation and schwannoma feasible, which will improve clinical management and benefit patient prognosis. KEY POINTS: • The "honeycomb" sign on HRCT is a reliable finding to differentiate GGVM from GGS. • GGVM typically shows "pattern A" enhancement (focal enhancement of the tumor on early dynamic T1WI, followed by progressive contrast filling of the tumor in the delayed phase), while "pattern B" enhancement (gradual heterogeneous or homogeneous enhancement of the whole lesion) is observed in GGS on dynamic T1WI.

Intraepithelial growth pattern for eyelid sebaceous carcinoma: a cohort of 214 patients from a single institution.

AIMS: To determine the distribution of three different intraepithelial growth patterns (pagetoid, bowenoid and papillary) in eyelid sebaceous carcinoma (SC) and correlate them with the clinical characteristics and prognosis. METHODS: A retrospective cohort study. The medical charts and pathological sections were retrospectively reviewed. All eligible patients were followed up for recurrence, metastasis and tumour-related mortality. The clinical significance of each intraepithelial growth pattern was determined by Cox regression. RESULTS: Of the 214 patients, 67 (31%) presented with intraepithelial invasion, among them, 34 (16%) were pagetoid, 27 (13%) were bowenoid and 6 (2.8%) were papillary. Patients of pagetoid intraepithelial spread showed significantly longer diagnostic delay (p=0.001) and more initial misdiagnoses of blepharitis (p=0.035). After a median follow-up period of 34.0 months, 67 (46%) patients in the non-intraepithelial group, 17 (50%) in the pagetoid group, 8 (30%) in the bowenoid group and 2 (33%) in the papillary group recurred. And 30 (20%) patients in the non-intraepithelial group, 9 (27%) in the pagetoid group and 4 (15%) in the bowenoid group developed metastasis. Moreover, 15 (10%) patients in the non-intraepithelial group, 6 (18%) in the pagetoid group and 1 (3.7%) in the bowenoid group died of SC. Cox regression indicated that pagetoid intraepithelial growth pattern was remarkably associated with increased chances of tumour-related mortality (HR=2.95, 95% CI 1.14 to 7.64, p=0.026). CONCLUSIONS: Intraepithelial tumour invasion was presented in nearly one third of patients with eyelid SC. Pagetoid intraepithelial neoplasia, the predominant growth pattern, significantly increased the risk of tumour-related mortality. Meticulous histopathological intraepithelial examination is recommended for every patient of eyelid SC. Special attention should be paid to those with pagetoid invasion, who may require more intensive managements.

Clinical application of the contrast-enhancement boost technique in computed tomography angiography of the portal vein.

PURPOSE: The aim of this study was to explore the improved image quality of the portal vein using the contrast-enhancement boost (CE-boost) technique for the improved visibility of abdominal-enhanced computed tomography (CT) scans in clinical practice. METHODS: This retrospective study included 50 patients in Group A who underwent routine abdominal-enhanced CT and 50 patients in Group B who underwent abdominal computed tomography angiography (CTA) with matched body mass index, age, and sex. Images in Group A were postprocessed with the CE-boost technique for further enhanced visibility of the portal vein. Both subjective and objective assessments of different branches of the portal vein in three types of images (i.e., Group A with CE-boost and without CE-boost, Group B) were statistically analyzed. RESULTS: The subjective scores of two experienced radiologists showed good consistency (kappa value > 0.624, p < 0.001), and the score of Group A with CE-boost (mean, 4.64) was significantly higher than that of the others (p < 0.001). The liver parenchyma and most target veins in Group A with CE-boost showed the highest CT, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) values and the lowest standard deviation (SD), while the CNR of most portal veins in Group A without CE-boost had the lowest CNR (p < 0.001). There were no differences in the SNR of the portal vein in Group A without CE-Boost and Group B (p > 0.05). CONCLUSION: CE-boost can significantly improve image quality in portal vein imaging without any additional scanning settings or changes in the clinical workflow.

Neddylation-mediated degradation of hnRNPA2B1 contributes to hypertriglyceridemia pancreatitis.

Hypertriglyceridemia-induced acute pancreatitis (HTGP) is characterized by the acute and excessive release of FFA produced by pancreatic lipases. However, the underlying mechanisms of this disease remain poorly understood. In this study, we describe the involvement of the RNA binding protein hnRNPA2B1 in the development of HTGP. We used palmitic acid (PA) and AR42J cells to create a model of HTGP in vitro. RT-PCR and western blot analyses revealed a decrease in the level of hnRNPA2B1 protein but not mRNA expression in PA-treated cells. Further analyses revealed that hnRNPA2B1 expression was regulated at the post-translational level by neddylation. Restoration of hnRNPA2B1 expression using the neddylation inhibitor MLN4924 protected AR42J cells from PA-induced inflammatory injury by preventing NF-κB activation and restoring fatty acid oxidation and cell proliferation. Furthermore, RNA immunoprecipitation studies demonstrated that hnRNPA2B1 orchestrates fatty acid oxidation by regulating the expression of the mitochondrial trifunctional protein-α (MTPα). Administration of MLN4924 in vivo restored hnRNPA2B1 protein expression in the pancreas of hyperlipidemic mice and ameliorated HTGP-associated inflammation and pancreatic tissue injury. In conclusion, we show that hnRNPA2B1 has a central regulatory role in preventing HTGP-induced effects on cell metabolism and viability. Furthermore, our findings indicate that pharmacological inhibitors that target neddylation may provide therapeutic benefits to HTGP patients.

DgCspC gene overexpression improves cotton yield and tolerance to drought and salt stress comparison with wild-type plants.

Drought and high salinity are key limiting factors for cotton quality and yield. Therefore, research is increasingly focused on mining effective genes to improve the stress resistance of cotton. Few studies have demonstrated that bacterial Cold shock proteins (Csps) overexpression can enhance plants stress tolerance. Here, we first identified and cloned a gene DgCspC encoding 88 amino acids (aa) with an open reading frame (ORF) of 264 base pairs (bp) from a Deinococcus gobiensis I-0 with high resistance to strong radiation, drought, and high temperature. In this study, heterologous expression of DgCspC promoted cotton growth, as exhibited by larger leaf size and higher plant height than the wild-type plants. Moreover, transgenic cotton lines showed higher tolerance to drought and salts stresses than wild-type plants, as revealed by susceptibility phenotype and physiological indexes. Furthermore, the enhanced stresses tolerance was attributed to high capacity of cellular osmotic regulation and ROS scavenging resulted from DgCspC expression modulating relative genes upregulated to cause proline and betaine accumulation. Meanwhile, photosynthetic efficiency and yield were significantly higher in the transgenic cotton than in the wild-type control under field conditions. This study provides a newly effective gene resource to cultivate new cotton varieties with high stresses resistance and yield.

METTL3 promotes the growth and metastasis of pancreatic cancer by regulating the m6A modification and stability of E2F5.

BACKGROUND: Pancreatic cancer belongs to lethal cancer with limited efficient treatment currently, and its main cause of death is rapid tumor growth and early metastasis. N6-methyladenosine (m6A) modification is a new method of epigenetic gene regulation involved in tumor progression, in which methyltransferase-like 3(METTL3) is the sole catalytic subunit. However, the role of METTL3 in pancreatic cancer remains to be explored. METHODS: m6A level was measured using MeRIP assay, and RT-qPCR and western blot were applied to determine mRNA and protein expression, respectively. Cellular behaviors were detected using CCK-8, EdU, wound healing and transwell assays. Xenograft assays were conducted to further verify the roles of METTL3 in pancreatic cancer. RESULTS: METTL3 was highly expressed in pancreatic cancer. However, downregulation of METTL3 restrained the viability, migration and invasion of pancreatic cancer cells. Moreover, E2F5 was found to be positively regulated by METTL3. Intriguingly, the anti-tumor functions of METTL3 knockdown in the phenotype of pancreatic cancer cells were overturned by overexpression of E2F5. Silencing METTL3 resulted in the decreased stability of E2F5 by methylating E2F5. CONCLUSIONS: In conclusion, METTL3 can promote the malignant progression of pancreatic cancer by modifying E2F5 through m6A methylation to promote its stability.

Cloning and function analysis of a Saussurea involucrata LEA4 gene.

Late embryogenesis abundant proteins (LEA) help adapt to adverse low-temperature environments. The Saussurea involucrate SiLEA4, which encodes a membrane protein, was significantly up-regulated in response to low temperature stress. Escherichia coli expressing SiLEA4 showed enhanced low-temperature tolerance, as evident from the significantly higher survival numbers and growth rates at low temperatures. Moreover, tomato strains expressing SiLEA4 had significantly greater freezing resistance, due to a significant increase in the antioxidase activities and proline content. Furthermore, they had higher yields due to higher water utilization and photosynthetic efficiency under the same water and fertilizer conditions. Thus, expressing SiLEA4 has multiple advantages: (1) mitigating chilling injury, (2) increasing yields, and (3) water-saving, which also indicates the great potential of the SiLEA4 for breeding applications.

Effect of Admission Serum Calcium Levels and Length of Stay in Patients with Acute Pancreatitis: Data from the MIMIC-III Database.

Objective: We retrospectively investigated the effect of admission serum calcium levels on length of stay (LOS) in patients hospitalized with acute pancreatitis (AP). Methods: Clinical data for 3156 patients diagnosed with AP were obtained from the Multiparametric Intelligent Monitoring in Intensive Care III (MIMIC-III) database. Restricted cubic spline curve (RCS) functions of dose-response analysis curves and logistic regression analysis were used to analyze the relationship between admission serum calcium levels and the LOS. Results: All patients were divided into 2 groups (<8.5 mg/dl group and ≥8.5 mg/dl group) based on RCS analysis. RCS showed a significant nonlinear negative correlation between blood calcium levels and the LOS (p < 0.001). In addition, compared with patients with blood calcium <8.5 mg/dl, multivariate logistic regression analysis showed that patients with blood calcium ≥8.5 mg/dl had a reduced risk of the LOS >2 days (aOR = 0.653; 95% CI 0.507-0.842; p=0.001), a reduced risk of the LOS >5 days (aOR = 0.589; 95% CI 0.503-0.689; p < 0.001), and a reduced risk of the LOS >7 days (aOR = 0.515; 95% CI 0.437-0.609; p < 0.001). And similar results were found in the subgroup analysis. Conclusion: Our findings suggest that low blood calcium increases the LOS in patients with AP. More attention is needed for patients with combined low blood calcium levels (<8.5 mg/dl) in hospitalized AP patients.

Explore the Mechanism of ß-Asarone on Improving Cognitive Dysfunction in Rats with Diabetic Encephalopathy.

Background: The number of people with diabetes is increasing, and many patients have significantly impaired cognitive function. For patients with diabetic encephalopathy (DE), simply lowering blood sugar does not improve learning and memory. Studies have shown that ß-asarone can significantly improve cognitive impairment in patients with DE, but the specific mechanism of action is unclear. Objective: This experiment hopes to use a variety of experimental methods to clarify the protective effect and mechanism of ß-asarone on brain neurons during the development of DE disease. Methods: A high-sugar and high-fat diet and streptozotocin injection-induced DE rat model was used. ß-asarone was administered for four weeks. The experiment used the Morris water maze test, biochemical index detection, and many methods to evaluate the neuroprotective effect of ß-asarone on DE rats from various aspects and understand its mechanism. Results: ß-asarone reduced neuronal cell damage and significantly improved the learning and memory ability of DE rats. In addition, ß-asarone can reduce the oxidative stress response and amyloid-ß accumulation in the brain of DE model rats and increase the content of brain-derived neurotrophic factor (BDNF) in the brain tissue, thereby reducing neuronal cell apoptosis and playing a protective role. Conclusion: ß-asarone can reduce the accumulation of oxidative stress and amyloid-ß in the brain, increase the content of BDNF, reduce the apoptosis of neuronal cells, and exert neuronal protection, thereby improving the learning and memory ability of DE model rats.

Black carbon-climate interactions regulate dust burdens over India revealed during COVID-19.

India as a hotspot for air pollution has heavy black carbon (BC) and dust (DU) loadings. BC has been identified to significantly impact the Indian climate. However, whether BC-climate interactions regulate Indian DU during the premonsoon season is unclear. Here, using long-term Reanalysis data, we show that Indian DU is positively correlated to northern Indian BC while negatively correlated to southern Indian BC. We further identify the mechanism of BC-dust-climate interactions revealed during COVID-19. BC reduction in northern India due to lockdown decreases solar heating in the atmosphere and increases surface albedo of the Tibetan Plateau (TP), inducing a descending atmospheric motion. Colder air from the TP together with warmer southern Indian air heated by biomass burning BC results in easterly wind anomalies, which reduces dust transport from the Middle East and Sahara and local dust emissions. The premonsoon aerosol-climate interactions delay the outbreak of the subsequent Indian summer monsoon.

Excess fatty acids induce pancreatic acinar cell pyroptosis through macrophage M1 polarization.

Free fatty acid derived from hyperlipidemia contributes to the development of inflammation in the pancreas. Here we explore the molecular mechanisms of fatty acid-induced pancreatitis through cellular experiments and the construction of a mouse model of hyperlipidemic pancreatitis. We found that palmitic acid stimulation leads to M1 polarization of macrophage, which secretes cathepsin S via exosomes to pancreatic acinar cells and leads to activation of the caspase1-mediated classical pyrolysis pathway, resulting in inflammation and pancreatic tissue damage. In vivo experiments have also demonstrated that the high levels of fatty acids induced by hyperlipidaemia exacerbate the development of pancreatitis, and that cathepsin S inhibitors significantly alleviate hyperlipidemic pancreatitis. Therefore, cathepsin S may be a new target for the clinical treatment of hyperlipidemic pancreatitis.

Double Trouble of Air Pollution by Anthropogenic Dust.

With urbanization worldwide in recent decades, anthropogenic dust (AD) emissions due to heavy urban construction and off-road vehicle use have been increasing. Its perturbations on urban air pollution at the global scale are still unclear. Based on observations, we found that a high urban AD optical depth is often accompanied by severe non-dust aerosol optical depth in the planetary boundary layer (PBL), both magnitudes even comparable. To investigate the causes, an AD emission inventory constrained by satellite retrievals is implemented in a global climate model. The results show that AD-induced surface radiative cooling of up to -15.9 ± 4.0 W m-2 regionally leads to reduced PBL height, which deteriorates non-dust pollution, especially over India and northern China, in addition to the tremendous direct AD contribution to pollutants. The estimated global total premature mortality due to AD is 0.8 million deaths per year and is more severe in populous regions.

Predictive value of the C-reactive protein/albumin ratio in severity and prognosis of acute pancreatitis.

Aim: To investigate the predictive value of C-reactive protein (CRP) to serum albumin (ALB) ratio in the severity and prognosis of acute pancreatitis (AP), and compare the predictive value of the CRP/ALB ratio with the Ranson score, modified computed tomography severity index (MCTSI) score, and Bedside Index of Severity in Acute Pancreatitis (BISAP) score. Methods: This cohort study retrospectively analyzed clinical data of AP patients from August 2018 to August 2020 in our hospital. Logistic regression analysis was utilized to determine the effects of CRP/ALB ratio, Ranson, MCTSI, and BISAP score on severe AP (SAP), pancreatic necrosis, organ failure, and death. The predictive values of CRP/ALB ratio, Ranson, MCTSI, and BISAP score were examined with the area under the curve (AUC) of the receiver operator characteristic (ROC) curve analysis. DeLong test was used to compare the AUCs between CRP/ALB ratio, Ranson, MCTSI, and BISAP score. Results: Totally, 284 patients were included in this study, of which 35 AP patients (12.32%) developed SAP, 29 (10.21%) organ failure, 30 (10.56%) pancreatic necrosis and 11 (3.87%) died. The result revealed that CRP/ALB ratio on day 2 was associated with SAP [odds ratio (OR): 1.74, 95% confidence interval (CI): 1.32 to 2.29], death (OR: 1.73, 95%CI: 1.24 to 2.41), pancreatic necrosis (OR: 1.28, 95%CI: 1.08 to 1.50), and organ failure (OR: 1.43, 95%CI: 1.18 to 1.73) in AP patients. Similarly, CRP/ALB on day 3 was related to a higher risk of SAP (OR: 1.50, 95%CI: 1.24 to 1.81), death (OR: 1.8, 95%CI: 1.34 to 2.65), pancreatic necrosis (OR: 1.22, 95%CI: 1.04 to 1.42), and organ failure (OR: 1.21, 95%CI: 1.04 to 1.41). The predictive value of CRP/ALB ratio for pancreatic necrosis was lower than that of MCTSI, for organ failure was lower than that of Ranson and BISAP, and for death was higher than that of MCTSI. Conclusion: The CRP/ALB ratio may be a novel but promising, easily measurable, reproducible, non-invasive prognostic score that can be used to predict SAP, death, pancreatic necrosis, and organ failure in AP patients, which can be a supplement of Ranson, MCTSI, and BISAP scores.