Clinical Characteristics, Management and Prognostic Factors of Immune Checkpoint Inhibitor-Associated Pneumonia in Chinese Cancer Patients.

OBJECTIVE: To investigate the clinical characteristics, treatment methods, outcomes, and variables influencing the outcomes of checkpoint inhibitor-related pneumonitis (CIP) among Chinese cancer patients. STUDY DESIGN: Descriptive Study. Place and Duration of the Study: Department of Pharmacy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China, from January 2019 to December 2022. METHODOLOGY: Patients with CIP were inducted. Clinical data including patient characteristics, ICI protocols; and the clinical features, treatments, and outcomes of CIP were collected and analysed. RESULTS: One hundred and forty-six patients were included. Median time to onset in the CIP was 17.0 weeks (range: 0.4 - 74.7). Mild CIP and severe CIP accounted for 84.93% and 15.07% of cases, respectively. All patients with CIP received methylprednisolone treatment, with an average starting dose of 1.64 mg/kg (0.59-6.00 mg/kg), and 79 (54.11%) of them received anti-infective therapy. One hundred and thirteen (77.04%) patients had improved symptoms of pneumonia, with only 33 (22.60%) patients displaying no improvement. Multivariate analysis revealed that the severity of CIP [OR = 0.167 (95% CI 0.061-0.461), p <0.001] and the starting dose of methylprednisolone [OR = 0.314 (95% CI 0.129-0.764), p <0.001] were independent predictors of outcomes of CIP, while the use of antibiotic was not. CONCLUSION: The severity of CIP and the initial dosage of methylprednisolone administered are significant factors that impact the outcomes of CIP in Chinese cancer patients after ICI treatment. Appropriate use of glucocorticoids and antibiotics is a necessary management strategy to control CIP effectively. KEY WORDS: Immune checkpoint inhibitors, Immune-related adverse events, Checkpoint inhibitor-related pneumonitis, Glucocorticosteroids, Antibiotics, Prognostic factors.

Molecular epidemiological characteristics of Mycobacterium leprae in highly endemic areas of China during the COVID-19 epidemic.

Objectives: The present study analyzed the impact of the COVID-19 pandemic on the prevalence and incidence of new leprosy cases, as well as the diversity, distribution, and temporal transmission of Mycobacterium leprae strains at the county level in leprae-endemic provinces in Southwest China. Methods: A total of 219 new leprosy cases during two periods, 2018-2019 and 2020-2021, were compared. We genetically characterized 83 clinical isolates of M. leprae in Guizhou using variable number tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). The obtained genetic profiles and cluster consequences of M. leprae were compared between the two periods. Results: There was an 18.97% decrease in the number of counties and districts reporting cases. Considering the initial months (January-March) of virus emergence, the number of new cases in 2021 increased by 167% compared to 2020. The number of patients with a delay of >12 months before COVID-19 (63.56%) was significantly higher than that during COVID-19 (48.51%). Eighty-one clinical isolates (97.60%) were positive for all 17 VNTR types, whereas two (2.40%) clinical isolates were positive for 16 VNTR types. The (GTA)9, (TA)18, (TTC)21 and (TA)10 loci showed higher polymorphism than the other loci. The VNTR profile of these clinical isolates generated five clusters, among which the counties where the patients were located were adjacent or relatively close to each other. SNP typing revealed that all clinical isolates possessed the single SNP3K. Conclusion: COVID-19 may have a negative/imbalanced impact on the prevention and control measures of leprosy, which could be a considerable fact for official health departments. Isolates formed clusters among counties in Guizhou, indicating that the transmission chain remained during the epidemic and was less influenced by COVID-19 preventative policies.

Assessment of vitamin D deficiency in recurrent BPPV patients: A cross-sectional study.

PURPOSE: This study aimed to investigate the vitamin D deficiency of patients with BPPV recurrence and to evaluate the differences of 25-hydroxy vitamin D (25(OH)D) and serum calcium levels among gender and age categories. METHODS: This cross-sectional study enrolled patients with BPPV. The diagnosis of BPPV was based on positional nystagmus and vertigo induced by certain head positions (The Dix-Hallpike maneuver and head roll tests). All patients' age, serum 25(OH)D, calcium measurements and recurrence data were collected and analyzed. RESULTS: The median of 25(OH)D was 15.32 (IQR 10.61, 20.90) ng/ml. The recurrent group showed lower 25(OH)D levels than that of non-recurrent group [13.28 (IQR 9.47, 17.57) ng/ml vs 16.21 (IQR 11.49, 21.13) ng/ml]. There were significant differences of 25(OH)D levels among age categories. The proportion of vitamin D deficiency in patients ≥60 years old was lower than that in the other two groups. CONCLUSION: Our study suggested that BPPV patients had a decreased 25(OH)D level and a high incidence of vitamin D deficiency. The 25(OH)D level of recurrent BPPV patients was lower than that in non-recurrent ones. Among them, the elderly group (≥60 years) took the preponderance, which had the lowest incidence of vitamin D deficiency and the highest incidence of vitamin D sufficiency.

Degradation of refractory organic matter in MBR effluent from treating landfill leachate by UV/PMS and UV/H2O2: a comparative study.

This study applied ultraviolet/peroxymonosulfate (UV/PMS) and UV/hydrogen peroxide (UV/H2O2) processes to the advanced treatment of membrane bioreactor (MBR) effluent. The degradation efficiency of refractory organic matter and the reaction mechanisms of the two processes were systematically investigated. The results showed that the degradation efficiency of the UV/PMS processes was significantly lower than that of the UV/H2O2 process when the PMS concentration was significantly lower than the H2O2 concentration, e.g. the UV254 removals under optimal conditions were 72.92% and 82.21%, respectively. Additionally, the UV/PMS process could operate over a broader pH range. The degradation efficiency of the UV/PMS process was slightly increased by HCO3- and Cl- due to the activation of PMS, while in the UV/H2O2 process, HCO3- and Cl- depressed the degradation efficiency by competing with organic matter to react with reactive oxygen species (ROS). After the two processes, the aromaticity, humification, condensation degree, and molecular weight of refractory organic matter in the MBR effluent were considerably decreased. Fulvic- (HA) and humic-like substances (FA) were greatly degraded by the two processes. The UV/PMS had a superior degradation efficiency for macromolecular HA in the early stage of the reaction, and the UV/H2O2 could degrade HA to protein-like substances in the latter stage of the reaction. These differences between the two processes could be attributed to the dominance of different ROS, with SO4•- and HO• dominating in the UV/PMS, and HO• dominating in the UV/H2O2. The results of this study provide theoretical support for the application of MBR effluent treatment.Highlights Comparison on the MBR effluent treatment of UV/PMS and UV/H2O2 is studied.UV/PMS process can better destroy humic-like substances in the early reaction stage.Humic-like substances are transformed into protein-like compounds in UV/H2O2 process.UV/PMS and UV/PMS performs differently due to their different dominant ROS.

Early prediction of drug-resistant epilepsy using clinical and EEG features based on convolutional neural network.

OBJECTIVE: Machine learning utilization in electroencephalogram (EEG) analysis and epilepsy care is fast evolving. Thus, we aim to develop and validate two one-dimensional convolutional neural network (CNN) algorithms for predicting drug-resistant epilepsy (DRE) in patients with newly-diagnosed epilepsy based on EEG and clinical features. METHODS: We included a total of 1010 EEG signal epochs and 15 clinical features from 101 patients with epilepsy. Each patient had 10 epochs of EEG signal data, with each signal recorded for 90 s. The ratio of development set and validation set was 80:20, and ten-fold cross validation was performed. First, a CNN algorithm was used to extract EEG features automatically. Then, Two one-dimensional CNNs were crafted.. Accuracy, specificity, precision, sensitivity, F1-score, kappa statistics, mean square error (MSE) and area under the curve (AUC) were calculated to evaluate the classifiers performance. RESULTS: The clinical-EEG model showed good performance and clinical practical value, with the accuracy, specificity, precision, sensitivity, F1-score, kappa statistics, best MSE and AUC in test set were 0.99, 0.72, 0.82, 0.96, 0.89, 0.83, 32.00, 0.81, respectively, and the accuracy in validation set was 0.84. In the EEG model, the accuracy, specificity, precision, sensitivity, F1-score, kappa statistics, best MSE and AUC in test set were 0.99, 0.59, 0.82, 0.90, 0.86, 0.72, 181.76, 0.76, respectively, and the accuracy in validation set was 0.81. CONCLUSION: We constructed a clinical-EEG model showed good potential for predicting DRE in patients with newly-diagnosed epilepsy, which could help identify patients at high risk of developing DRE at earlier stages.

Intranasal administration of recombinant prosaposin attenuates neuronal apoptosis through GPR37/PI3K/Akt/ASK1 pathway in MCAO rats.

Studies have reported that Prosaposin (PSAP) is neuroprotective in cerebrovascular diseases. We hypothesized that PSAP would reduce infarct volume by attenuating neuronal apoptosis and promoting cell survival through G protein-coupled receptor 37(GPR37)/PI3K/Akt/ASK1 pathway in middle cerebral artery occlusion (MCAO) rats. Two hundred and thirty-five male and eighteen female Sprague-Dawley rats were used. Recombinant human PSAP (rPSAP) was administered intranasally 1 h (h) after reperfusion. PSAP small interfering ribonucleic acid (siRNA), GPR37 siRNA, and PI3K specific inhibitor LY294002 were administered intracerebroventricularly 48 h before MCAO. Infarct volume, neurological score, immunofluorescence staining, Western blot, Fluoro-Jade C (FJC) and TUNEL staining were examined. The expression of endogenous PSAP and GPR37 were increased after MCAO. Intranasal administration of rPSAP reduced brain infarction, neuronal apoptosis, and improved both short- and long-term neurological function. Knockdown of endogenous PSAP aggravated neurological deficits. Treatment with exogenous rPSAP increased PI3K expression, Akt and ASK1 phosphorylation, and Bcl-2 expression; phosphorylated-JNK and Bax levels were reduced along with the number of FJC and TUNEL positive neurons. GPR37 siRNA and LY294002 abolished the anti-apoptotic effect of rPSAP at 24 h after MCAO. In conclusion, rPSAP attenuated neuronal apoptosis and improved neurological function through GPR37/PI3K/Akt/ASK1 pathway after MCAO in rats. Therefore, further exploration of PSAP as a potential treatment option in ischemic stroke is warranted.

Effect of DHCR7 on adipocyte differentiation in goats.

Cholesterol is regarded as a signaling molecule in regulating the metabolism and function of fat cells, in which 7-Dehydrocholesterol reductase (DHCR7) is a key enzyme that catalyzes the conversion of 7-dehydrocholesterol to cholesterol, however, the exact function of DHCR7 in goat adipocytes remains unknown. Here, the effect of DHCR7 on the formation of subcutaneous and intramuscular fat in goats was investigated in vitro, and the result indicated that the mRNA level of DHCR7 showed a gradual downward trend in subcutaneous adipogenesis, but an opposite trend in intramuscular adipogenesis. In the process of subcutaneous preadipocytes differentiation, overexpression of DHCR7 inhibited the expression of adipocytes differentiation marker genes (CEBP/α, CEBP/ß, SREBP1 and AP2), lipid metabolism-related genes (AGPAT6, FASN, SCD1 and LPL), and the lipid accumulation. However, in intramuscular preadipocyte differentiation, DHCR7 overexpression showed a promoting effect on adipocyte differentiation marker genes (CEBP/α, CEBP/ß, PPARγ and SREBP1) and lipid metabolism-related genes (GPAM, AGPAT6, DGAT1 and SCD1) expression, and on lipid accumulation. In summary, our work demonstrated that DHCR7 played an important role in regulating adipogenic differentiation and lipid metabolism in preadipocytes in goats, which is of great significance for uncovering the underlying molecular mechanism of adipocyte differentiation and improving goat meat quality.

Decoding the Pathway-Dependent Self-Assembly of Polymer-Grafted Nanoparticles by Ligand Crystallization.

Functional metamaterials can be constructed by assembling nanoparticles (NPs) into well-ordered structures, which show fascinating properties at different length scales. Using polymer-grafted NPs (PGNPs) as a building block, flexible composite metamaterials can be obtained, of which the structure is significantly affected by the property of polymer ligands. Here, it is demonstrated that the crystallization of polymer ligands determines the assembly behavior of NPs and reveal a pathway-dependent self-assembly of PGNPs into different metastructures in solution. By changing the crystallization degree of polymer ligands, the arrangement structure of NPs can be tailored. When the polymer ligands highly crystallize, the PGNPs assemble into diamond-shaped platelets, in which the NPs arrange disorderedly. When the polymer ligands lowly crystallize, the PGNPs assemble into highly ordered 3D superlattices, in which the NPs pack into a body-centered-cubic structure. The structure transformation of PGNP assemblies can be achieved by thermal annealing to regulate the crystallization of polymer ligands. Interestingly, the diamond-shaped platelets remain "living" for seeded epitaxial growth of newly added crystalline species. This work demonstrates the effects of ligand crystallization on the crystallization of NP, providing new insights into the structure regulation of metamaterials.

Low vitamin D and uric acid status in patients with benign paroxysmal positional vertigo.

PURPOSE: Growing evidence reported that vitamin D and uric acid metabolism played roles in the occurrence of benign paroxysmal positional vertigo, an otoconia-related vestibular disorder. We aimed to investigate the serum 25-hydroxy vitamin D (25(OH)D) and uric acid in patients with benign paroxysmal positional vertigo and to determine the risk factor for benign paroxysmal positional vertigo. METHODS: This case-control study comprised 182 patients with benign paroxysmal positional vertigo and 182 age- and gender-matched controls. All subjects' age, body mass index, systolic blood pressure, diastolic blood pressure, 25-hydroxyvitamin D (25(OH)D), uric acid and serum calcium measurements were analyzed. RESULTS: We found a female preponderance of benign paroxysmal positional vertigo patients, with a median of 60 (52-66) years old. The results showed low vitamin D status both in benign paroxysmal positional vertigo and controls, with no significant difference of 25(OH)D levels between benign paroxysmal positional vertigo patients and controls (P > 0.05). Compared with the control group, patients with benign paroxysmal positional vertigo had a higher prevalence of vitamin D deficiency and a lower prevalence of vitamin D sufficiency (P < 0.05). Uric acid was significantly lower in the benign paroxysmal positional vertigo groups (P < 0.05). Logistic regression analysis revealed that age and uric acid were considered higher risk predictors for benign paroxysmal positional vertigo. CONCLUSION: Our study observed low vitamin D status in patients with benign paroxysmal positional vertigo, with no significant differences of the 25(OH)D level in patients with benign paroxysmal positional vertigo and controls. Elderly, vitamin D deficiency and low uric acid levels may be risk factors for benign paroxysmal positional vertigo occurrence.

Highly sensitive and rapid determination of Mycobacterium leprae based on real-time multiple cross displacement amplification.

BACKGROUND: Mycobacterium leprae (ML) is the pathogen that causes leprosy, which has a long history and still exists today. ML is an intracellular mycobacterium that dominantly induces leprosy by causing permanent damage to the skin, nerves, limbs and eyes as well as deformities and disabilities. Moreover, ML grows slowly and is nonculturable in vitro. Given the prevalence of leprosy, a highly sensitive and rapid method for the early diagnosis of leprosy is urgently needed. RESULTS: In this study, we devised a novel tool for the diagnosis of leprosy by combining restriction endonuclease, real-time fluorescence analysis and multiple cross displacement amplification (E-RT-MCDA). To establish the system, primers for the target gene RLEP were designed, and the optimal conditions for E-RT-MCDA at 67 °C for 36 min were determined. Genomic DNA from ML, various pathogens and clinical samples was used to evaluate and optimize the E-RT-MCDA assay. The limit of detection (LoD) was 48.6 fg per vessel for pure ML genomic DNA, and the specificity of detection was as high as 100%. In addition, the detection process could be completed in 36 min by using a real-time monitor. CONCLUSION: The E-RT-MCDA method devised in the current study is a reliable, sensitive and rapid technique for leprosy diagnosis and could be used as a potential tool in clinical settings.

Entropy-driven formation of binary superlattices assembled from polymer-tethered nanorods and nanospheres.

Integrating binary mixtures of nanoparticles (NPs) into well-defined superstructures gives rise to novel collective properties depending on the shapes and individual properties of both species. In this paper, we studied the entropy-driven formation of binary superlattices assembled from polymer-tethered nanorods and nanospheres. The results indicated that the conformational entropy of the polymer chains and the mixing entropy of the nanorods and nanospheres are two parameters that determine the formation of binary superlattices.

Biosensor-Based Multiple Cross Displacement Amplification for the Rapid Detection of Mycobacterium leprae.

Leprosy is an ancient disease caused by Mycobacterium leprae (ML) that remains a public health problem in poverty-stricken areas worldwide. Although many ML detection techniques have been used, a rapid and sensitive tool is essential for the early detection and treatment of leprosy. Herein, we developed a rapid ML detection technique by combining multiple cross displacement amplification (MCDA) with a nanoparticle-based lateral flow biosensor (LFB), termed ML-MCDA-LFB. MCDA induced a rapid isothermal reaction using specific primers targeting the RLEP gene, and the LFB enabled instant visual amplicon detection. The pure genomic DNA of ML and nucleic acids from various pathogens were employed to evaluate and optimize the ML-MCDA-LFB assay. The optimal conditions for ML-MCDA-LFB were 68 °C and 35 min, respectively. The limit of detection for pure ML genomic DNA was 150 fg per vessel, and the specificity of detection was 100% for the experimental strains. Additionally, the entire detection process could be performed within 40 min, including the isothermal amplification (35 min) and result confirmation (1-2 min). Hence, the ML-MCDA-LFB assay was shown to be a rapid, sensitive, and visual method for detecting ML and could be used as a potential tool for early clinical diagnosis and field screening of leprosy.

RNF20/RNF40 ameliorates streptozotocin-induced type 1 diabetes by activating vitamin D receptors in vivo.

BACKGROUND: Type 1 diabetes is one of the chronic autoimmune diseases. Its features include the immune-triggered pancreatic beta-cells destruction. Ubiquitin ligases RNF20 and RNF40 have been discovered to participate into beta cells gene expression, insulin secretion, and expression of vitamin D receptors (VDRs). However, no reports about the role of RNF20/RNF40 in type 1 diabetes are known till now. The aim of this study was to clarify the role of RNF20/RNF40 in type 1 diabetes and explore the mechanism. METHODS: In this study, streptozotocin (STZ)-induced mice type 1 diabetes model was used. The protein expressions of genes were examined through Western blot analysis. Fasting blood glucose was detected through glucose meter. The plasma insulin was tested through the commercial kit. Hematoxylin and eosin staining was utilized to observe pathological changes of pancreatic tissues. Immunofluorescence assay was performed to evaluate the level of insulin. The levels of pro-inflammatory cytokines in serum were assessed by enzyme-linked-immunosorbent serologic assay. The cell apoptosis was measured through terminal deoxynucleotidyl transferase dUTP nick end labelling assay. RESULTS: STZ was used to stimulate mice model for type 1 diabetes. At first, both RNF20 and RNF40 expressions were down-regulated in STZ-mediated type 1 diabetes. Additionally, RNF20/RNF40 improved hyperglycemia in STZ-stimulated mice. Moreover, RNF20/RNF40 relieved pancreatic tissue injury in STZ-induced mice. Further experiments found that RNF20/RNF40 rescued the strengthened inflammation mediated by STZ treatment. The cell apoptosis was enhanced in the pancreatic tissues of STZ-triggered mice, but this effect was weakened by overexpression of RNF20/RNF40. Besides, the VDR expression was positively regulated by RNF20/RNF40. Finally, VDR knockdown reversed improved hyperglycemia, inflammation, and cell apoptosis stimulated by overexpression of RNF20/RNF40. CONCLUSION: Our findings proved that RNF20/RNF40 activated VDR to relieve type 1 diabetes. This work might highlight the functioning of RNF20/RNF40 in the treatment of type 1 diabetes.

Impact of COVID-19 prevention and control on tuberculosis and scarlet fever in China's Guizhou.

China has implemented a series of long-term measures to control the spread of COVID-19, however, the effects of these measures on other chronic and acute respiratory infectious diseases remain unclear. Tuberculosis (TB) and scarlet fever (SF) serve as representatives of chronic and acute respiratory infectious diseases, respectively. In China's Guizhou province, an area with a high prevalence of TB and SF, approximately 40,000 TB cases and hundreds of SF cases are reported annually. To assess the impact of COVID-19 prevention and control on TB and SF in Guizhou, the exponential smoothing method was employed to establish a prediction model for analyzing the influence of COVID-19 prevention and control on the number of TB and SF cases. Additionally, spatial aggregation analysis was utilized to describe spatial changes in TB and SF before and after the COVID-19 outbreak. The parameters of the TB and SF prediction models are R2 = 0.856, BIC = 10.972 and R2 = 0.714, BIC = 5.325, respectively. TB and SF cases declined rapidly at the onset of COVID-19 prevention and control measures, with the number of SF cases decreasing for about 3-6 months and the number of TB cases remaining in decline for 7 months after the 11th month. The spatial aggregation of TB and SF did not change significantly before and after the COVID-19 outbreak but exhibited a marked decrease. These findings suggest that China's COVID-19 prevention and control measures also reduced the prevalence of TB and SF in Guizhou. These measures may have a long-term positive impact on TB, but a short-term effect on SF. Areas with high TB prevalence may continue to experience a decline due to the implementation of COVID-19 preventive measures in the future.

Epidemiological characteristics of pulmonary tuberculosis among students in Guizhou, China: a retrospective study from 2010 to 2020.

OBJECTIVE: We described epidemiological characteristics of pulmonary tuberculosis (PTB) among students and evaluated susceptible populations and areas in Guizhou province and also to provide scientific suggestions for prevention and control. SETTING: Guizhou, China. DESIGN: This is a retrospective epidemiological study on PTB in students. METHODS: Data are from the China Information System for Disease Control and Prevention. We collected all PTB cases among the student population from 2010 to 2020 in Guizhou. Incidence, composition ratio and hotspot analysis were used to describe epidemiological and some clinical characteristics. RESULTS: A total of 37 147 new student PTB cases were registered among the population aged 5-30 years during 2010-2020. The proportions of men and women were 53.71% and 46.29%, respectively. Cases aged 15-19 years dominated (63.91%), and the proportion of ethnic groups was increasing during the period. Generally, the raw annual incidence of PTB among the population was increasing from 32.585 per 100 000 persons in 2010 to 48.872 per 100 000 persons in 2020 (c 2 trend=1283.230, p<0.001). March and April were the peak months of a year, and cases were clearly grouped in Bijie city. New cases were mainly identified via physical examination, and cases from active screening were still low (0.76%). Additionally, secondary PTB accounted for 93.68%, positive rate of pathogen was only 23.06%, and the recovery rate was 94.60%. CONCLUSIONS: The population aged 15-19 years is the vulnerable population, and Bijie city is the susceptible area. BCG vaccination and promotion for active screening should be the priority of futural PTB prevention and control. Tuberculosis laboratory capacity should be improved.

Single-Dose Rifapentine in Household Contacts of Patients with Leprosy.

BACKGROUND: Previous studies have suggested that a single dose of rifampin has protective effects against leprosy in close contacts of patients with the disease. Rifapentine was shown to have greater bactericidal activity against Mycobacterium leprae than rifampin in murine models of leprosy, but data regarding its effectiveness in preventing leprosy are lacking. METHODS: We conducted a cluster-randomized, controlled trial to investigate whether single-dose rifapentine is effective in preventing leprosy in household contacts of patients with leprosy. The clusters (counties or districts in Southwest China) were assigned to one of three trial groups: single-dose rifapentine, single-dose rifampin, or control (no intervention). The primary outcome was the 4-year cumulative incidence of leprosy among household contacts. RESULTS: A total of 207 clusters comprising 7450 household contacts underwent randomization; 68 clusters (2331 household contacts) were assigned to the rifapentine group, 71 (2760) to the rifampin group, and 68 (2359) to the control group. A total of 24 new cases of leprosy occurred over the 4-year follow-up, for a cumulative incidence of 0.09% (95% confidence interval [CI], 0.02 to 0.34) with rifapentine (2 cases), 0.33% (95% CI, 0.17 to 0.63) with rifampin (9 cases), and 0.55% (95% CI, 0.32 to 0.95) with no intervention (13 cases). In an intention-to-treat analysis, the cumulative incidence in the rifapentine group was 84% lower than that in the control group (cumulative incidence ratio, 0.16; multiplicity-adjusted 95% CI, 0.03 to 0.87; P = 0.02); the cumulative incidence did not differ significantly between the rifampin group and the control group (cumulative incidence ratio, 0.59; multiplicity-adjusted 95% CI, 0.22 to 1.57; P = 0.23). In a per-protocol analysis, the cumulative incidence was 0.05% with rifapentine, 0.19% with rifampin, and 0.63% with no intervention. No severe adverse events were observed. CONCLUSIONS: The incidence of leprosy among household contacts over 4 years was lower with single-dose rifapentine than with no intervention. (Funded by the Ministry of Health of China and the Chinese Academy of Medical Sciences; Chinese Clinical Trial Registry number, ChiCTR-IPR-15007075.).

Entropically Driven Fabrication of Binary Superlattices Assembled from Polymer-Tethered Nanocubes and Nanospheres.

The spontaneous organization of two types of nanoparticles (NPs) with different shapes or properties into binary nanoparticle superlattices (BNSLs) with different configurations has recently attracted significant attention due to the coupling or synergistic effect of the two types of NPs, providing an efficient and general route for designing new functional materials and devices. Here, this work reports the co-assembly of polystyrene (PS) tethered anisotropic gold nanocubes (AuNCs@PS) and isotropic gold NPs (AuNPs@PS) via an emulsion-interface self-assembly strategy. The distributions and arrangements of the AuNCs and spherical AuNPs in the BNSLs can be precisely controlled by adjusting the effective size ratio (λeff ) of the effective diameter (deff ) of the embedded spherical AuNPs to the polymer gap size (L) between the neighboring AuNCs. λeff determines not only the change of the conformational entropy of the grafted polymer chains (∆Scon ) but also the mixing entropy (∆Smix ) of the two types of NPs. During the co-assembly process, ∆Smix tends to be as high as possible, and the -∆Scon tends to be as low as possible, leading to free energy minimization. As a result, well-defined BNSLs with controllable distributions of spherical and cubic NPs can be obtained by tuning λeff . This strategy can also be applied for other NPs with different shapes and atomic properties, thus largely enriching the BNSL library and enabling the fabrication of multifunctional BNSLs, which have potential applications in photothermal therapy, surface-enhanced Raman scattering, and catalysis.

RNF20/RNF40 ameliorates streptozotocin-induced type 1 diabetes by activating vitamin D receptors in vivo

Background: Type 1 diabetes is one of the chronic autoimmune diseases. Its features include the immune-triggered pancreatic beta-cells destruction. Ubiquitin ligases RNF20 and RNF40 have been discovered to participate into beta cells gene expression, insulin secretion, and expression of vitamin D receptors (VDRs). However, no reports about the role of RNF20/RNF40 in type 1 diabetes are known till now. The aim of this study was to clarify the role of RNF20/RNF40 in type 1 diabetes and explore the mechanism. Methods: In this study, streptozotocin (STZ)-induced mice type 1 diabetes model was used. The protein expressions of genes were examined through Western blot analysis. Fasting blood glucose was detected through glucose meter. The plasma insulin was tested through the commercial kit. Hematoxylin and eosin staining was utilized to observe pathological changes of pancreatic tissues. Immunofluorescence assay was performed to evaluate the level of insulin. The levels of pro-inflammatory cytokines in serum were assessed by enzyme-linked-immunosorbent serologic assay. The cell apoptosis was measured through terminal deoxynucleotidyl transferase dUTP nick end labelling assay. Results: STZ was used to stimulate mice model for type 1 diabetes. At first, both RNF20 and RNF40 expressions were down-regulated in STZ-mediated type 1 diabetes. Additionally, RNF20/RNF40 improved hyperglycemia in STZ-stimulated mice. Moreover, RNF20/RNF40 relieved pancreatic tissue injury in STZ-induced mice. Further experiments found that RNF20/RNF40 rescued the strengthened inflammation mediated by STZ treatment. The cell apoptosis was enhanced in the pancreatic tissues of STZ-triggered mice, but this effect was weakened by overexpression of RNF20/RNF40 (AU)

Self-assembly of anisotropy gold nanocubes into large area two-dimensional monolayer superlattices.

The spontaneous self-assembly of metal nanocrystals into two-dimensional (2D) monolayer superlattices with highly ordered symmetry and configuration paves the way towards the fabrication of functional materials. However, there remains great challenge for anisotropic nanocrystals to self-assembly into high quality superlattice because of the orientation and configuration consistency. Here, a facile yet universal solvent annealing driven 2D interfacial assembly of synthetic dried metal nanocrystals is firstly developed to realize the construction of the non-close-packing 2D monolayer gold nanocube (AuNC) superlattice with tunable interparticle distance and internal configurations (i.e. face-to-face and hexagonally-packed arrangement), which is achieved by precisely controlling molecular weight of polymer ligands tethered on AuNCs and the van der Waals forces between the adjacent AuNCs. In addition, the scale of the generated 2D monolayer AuNC superlattice with highly ordered internal arrangement and orientation can reach up to hundreds of micrometers, thus acquiring significant surface-enhanced Raman scattering performance of the large scale superlattice due to the strong plasma coupling effect. This strategy not only provides a robust route to fabricate nanocrystal superlattice structures but also offers a promising platform for preparing diverse functional materials with potential applications in electronics, photonics, detections, and others.

Uniform Nanorods with Regioselective Distribution of Inorganic Nanoparticles Templated by 2D Block Copolymer Nanosheets.

The inorganic/organic hybrid materials with regioselective distribution of functional inorganic nanoparticles (NPs) have received constant interest attributed to fascinating integrated properties. However, there remains a formidable challenge in realizing the regioselective distribution of NPs for the specific hybrid nanorods. Herein, we report the construction of uniform core-shell hybrid nanorods with the regioselective distribution of inorganic NPs by selectively disassembling the prepared NPs/polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) hybrid nanosheets. Moreover, through precisely adjusting the parameters, such as complexation ability between the metal precursor and P4VP blocks, the protonation degree of P4VP blocks and complexation time, the NPs/polymer core-shell hybrid nanorod with the uniform distribution of NPs, and dumbbell-like hybrid nanorods with selective distribution of NPs at both ends can be obtained. This finding reveals a unique insight into the design of the anisotropic functional hybrid materials with the regioselective distribution of inorganic NPs.