Unacylated ghrelin attenuates acute liver injury and hyperlipidemia via its anti-inflammatory and anti-oxidative activities.

Objectives: Liver injury and hyperlipidemia are major issues that have drawn more and more attention in recent years. The present study aimed to investigate the effects of unacylated ghrelin (UAG) on acute liver injury and hyperlipidemia in mice. Materials and Methods: UAG was injected intraperitoneally once a day for three days. Three hours after the last administration, acute liver injury was induced by intraperitoneal injection of carbon tetrachloride (CCl4), and acute hyperlipidemia was induced by intraperitoneal injection of poloxamer 407, respectively. Twenty-four hours later, samples were collected for serum biochemistry analysis, histopathological examination, and Western blotting. Results: In acute liver injury mice, UAG significantly decreased liver index, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), reduced malondialdehyde (MDA) concentration and increased superoxide dismutase(SOD) in liver tissue. NF-kappa B (NF-κB) protein expression in the liver was down-regulated. In acute hyperlipidemia mice, UAG significantly decreased serum total cholesterol (TC), triglyceride (TG), ALT, and AST, as well as hepatic TG levels. Meanwhile, hepatic MDA decreased and SOD increased significantly. Moreover, UAG improved the pathological damage in the liver induced by CCl4 and poloxamer 407, respectively. Conclusion: Intraperitoneal injection of UAG exhibited hepatoprotective and lipid-lowering effects on acute liver injury and hyperlipidemia, which is attributed to its anti-inflammatory and anti-oxidant activities.

Spacer Engineering Enables Fine-Tuned Thin Film Microstructure and Efficient Charge Transport for Ultrasensitive 2D Perovskite-Based Heterojunction Phototransistors and Optoelectronic Synapses.

2D Ruddlesden-Popper phase layered perovskites (RPLPs) hold great promise for optoelectronic applications. In this study, a series of high-performance heterojunction phototransistors (HPTs) based on RPLPs with different organic spacer cations (namely butylammonium (BA+), cyclohexylammonium (CyHA+), phenethylammonium (PEA+), p-fluorophenylethylammonium (p-F-PEA+), and 2-thiophenethylammonium (2-ThEA+)) are fabricated successfully, in which high-mobility organic semiconductor 2,7-dioctyl[1]benzothieno[3,2-b]benzothiophene is adopted to form type II heterojunction channels with RPLPs. The 2-ThEA+-RPLP-based HPTs show the highest photosensitivity of 3.18 × 107 and the best detectivity of 9.00 × 1018 Jones, while the p-F-PEA+-RPLP-based ones exhibit the highest photoresponsivity of 5.51 × 106 A W-1 and external quantum efficiency of 1.32 × 109%, all of which are among the highest reported values to date. These heterojunction systems also mimicked several optically controllable fundamental characteristics of biological synapses, including excitatory postsynaptic current, paired-pulse facilitation, and the transition from short-term memory to long-term memory states. The device based on 2-ThEA+-RPLP film shows an ultra-high PPF index of 234%. Moreover, spacer engineering brought fine-tuned thin film microstructures and efficient charge transport/transfer, which contributes to the superior photodetection performance and synaptic functions of these RPLP-based HPTs. In-depth structure-property correlations between the organic spacer cations/RPLPs and thin film microstructure/device performance are systematically investigated.

Spatiotemporally Comparative Analysis of HIV, Pulmonary Tuberculosis, HIV-Pulmonary Tuberculosis Coinfection in Jiangsu Province, China.

Purpose: Pulmonary tuberculosis (PTB) is a severe chronic communicable disease that causes a heavy disease burden in China. Human Immunodeficiency Virus (HIV) and PTB coinfection dramatically increases the risk of death. This study analyzes the spatiotemporal dynamics of HIV, PTB and HIV-PTB coinfection in Jiangsu Province, China, and explores the impact of socioeconomic determinants. Patients and Methods: The data on all notified HIV, PTB and HIV-PTB coinfection cases were extracted from Jiangsu Provincial Center for Disease Control and Prevention. We applied the seasonal index to identify high-risk periods of the disease. Time trend, spatial autocorrelation and SaTScan were used to analyze temporal trends, hotspots and spatiotemporal clusters of diseases. The Bayesian space-time model was conducted to examine the socioeconomic determinants. Results: The case notification rate (CNR) of PTB decreased from 2011 to 2019 in Jiangsu Province, but the CNR of HIV and HIV-PTB coinfection had an upward trend. The seasonal index of PTB was the highest in March, and its hotspots were mainly distributed in the central and northern parts, such as Xuzhou, Suqian, Lianyungang and Taizhou. HIV had the highest seasonal index in July and HIV-PTB coinfection had the highest seasonal index in June, with their hotspots mainly distributed in southern Jiangsu, involving Nanjing, Suzhou, Wuxi and Changzhou. The Bayesian space-time interaction model showed that socioeconomic factor and population density were negatively correlated with the CNR of PTB, and positively associated with the CNR of HIV and HIV-PTB coinfection. Conclusion: The spatial heterogeneity and spatiotemporal clusters of PTB, HIV and HIV-PTB coinfection are exhibited obviously in Jiangsu. More comprehensive interventions should be applied to target TB in the northern part. While in southern Jiangsu, where the economic level is well-developed and the population density is high, we should strengthen the prevention and control of HIV and HIV-PTB coinfection.

Manipulating Polymer Backbone Configuration via Halogenated Asymmetric End-Groups Enables Over 18% Efficiency All-Polymer Solar Cells.

High-performance all-polymer solar cells (all-PSCs) deeply rely on the joint contributions of desirable optical absorption, adaptive energy levels, and appropriate morphology. Herein, two structural analogous polymerized small-molecule acceptors (PSMAs), PYFCl-T and PYF&PYCl-T, are synthesized, and then incorporated into the PM6:PY-IT binary blends to construct ternary all-PSCs. Due to the superior compatibility of PY-IT and PYFCl-T, the ternary all-PSC based on PM6:PY-IT:PYFCl-T with 10 wt% PYFCl-T, presents higher and more balanced charge mobility, suppressed charge recombination, and faster charge-transfer kinetics, resulting in an outstanding power conversion efficiency (PCE) of 18.12% with enhanced Jsc and FF, which is much higher than that (PCE of 16.09%) of the binary all-PSCs based on PM6:PY-IT. Besides, the ternary all-PSCs also exhibit improved photostability. The conspicuous performance enhancement principally should give the credit to the miscibility-driven phase optimization of the donor and acceptor. These findings highlight the significance of polymer-backbone configuration modulation of PSMAs in morphology optimization toward boosting the device properties of all-PSCs.

Serum LDL-C/HDL-C ratio and the risk of carotid plaques: a longitudinal study.

BACKGROUND: Dyslipidemia contributes to an increased risk of carotid atherosclerosis. However, the association between the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) and carotid plaque formation has not been well documented. This study aims to assess the role of LDL-C/HDL-C in the risk of carotid plaque formation in a Chinese population. METHODS: We followed 2,191 participants who attended the annual routine health examination. Cox proportional hazards regression, restricted cubic spline (RCS), and subgroup analysis were applied to evaluate the association between the LDL-C/HDL-C ratio and carotid plaques. The hazard ratio (HR) and 95% confidence interval (CI) were used to estimate the strength of the association. RESULTS: Among 2,191 participants, 388 had incident carotid plaques detected, with a median follow-up time of 1.05 years. Compared with subjects younger than 45 years, those aged 45 to 59 years (HR: 2.00, 95% CI: 1.55-2.58) and over 60 years (HR: 3.36, 95% CI: 2.47-4.58) had an increased risk of carotid plaque formation. Males (HR: 1.26, 95% CI: 1.01-1.56), diabetes (HR: 1.46, 95% CI: 1.06-2.01) and a high LDL-C/HDL-C ratio (HR: 1.22, 95% CI: 1.07-1.38) were significantly linked with the occurrence of carotid plaques. After adjusting for potential confounding factors, we observed that a high LDL-C/HDL-C ratio promoted carotid plaque events (HR: 1.30, 95% CI: 1.12-1.50). The RCS analysis revealed a significant nonlinear association. The association was stronger among females (P-interaction < 0.05). CONCLUSION: A high LDL-C/HDL-C ratio could accelerate the occurrence of carotid plaques. Older men with diabetes and dyslipidemia are the critical target population. Women may be more likely to benefit from lipid-lowering interventions and thus avoid carotid plaque formation.

Preparation of Black pepper (Piper nigrum L.) essential oil nanoparticles and its antitumor activity on triple negative breast cancer in vitro.

The active compounds isolated from Black pepper have anticancer effects, but the bioactivity of Black pepper essential oil (BP-EO) is rarely studied. BP-EO has poor stability and a suitable dose form should be prepared for in vivo delivery. Triple negative breast cancer (TNBC) has attracted more and more attention due to its high mitotic index, high metastasis rate and poor prognosis. In this study, the composition of BP-EO was analyzed by gas chromatography-mass spectrometry (GC-MS), and nanoparticles (NPs) loaded with BP-EO were prepared by nanoprecipitation method using Eudragit L100 as a carrier. We investigated the preparation, characterization, stability and in vitro release of nanoparticles. MTT assay, cell wound healing, Transwell invasion assay and Western blot were used to study the anti-tumor effect and mechanism of MDA-MB-231 cells. The GC-MS analysis identified a total of 33 compounds among which alkenes account for 63.55%. The prepared BP-EO NPs exhibited nanoscale morphology, good stability and pH-responsive and sustained release character which is suitable for in vivo delivery. BP-EO NPs significantly inhibited the proliferation, migration and invasion of MDA-MB-231 cells. Furthermore, BP-EO NPs significantly inhibited the expressions of Wnt and ß-catenin and significantly activated the expression of GSK-3ß in MDA-MB-231 cells. Therefore, BP-EO NPs prepared in this study provide a new effective strategy for the treatment of TNBC. PRACTICAL APPLICATIONS: Black pepper is rich in essential oil and has excellent antioxidant and antibacterial activities. However, the anti-tumor activity of BP-EO has not been studied. In this study, we found that BP-EO has excellent anticancer activity. To achieve effective encapsulation of black pepper essential oil and an excellent anti-triple negative breast cancer activity, nanoparticles loaded with BP-EO were prepared using Eudragit L100 as the carrier by the nanoprecipitation method. The in vitro study revealed that BP-EO NPs inhibited proliferation, migration and invasion of MDA-MB-231 cells via inhibiting the Wnt/ß-Catenin signaling pathway. This study provides new ideas and innovations for the treatment of invasive triple negative breast cancer in the future. At the same time, we will further reveal the application potential, pharmacokinetic characteristics and precise mechanism of BP-EO NPs in vivo in subsequent studies.

Tuberculosis reinfection and relapse in eastern China: a prospective study using whole-genome sequencing.

OBJECTIVES: Tuberculosis recurrence after an initial successful treatment episode can occur from either reinfection or relapse. In a population-based sample and whole genome sequencing in eastern China, we aimed to evaluate risk factors for tuberculosis recurrence and assess the proportion of recurrence because of either reinfection or relapse. METHODS: Successfully treated pulmonary tuberculosis patients with sputum culture positive results were recruited from five cities in Jiangsu Province from 2013 to 2015 and followed for 2 years for tuberculosis recurrence. Among patients developing a second tuberculosis episode, whole genome sequencing was performed to distinguish relapse or reinfection through a distance threshold of 6-single-nucleotide polymorphisms. We analyzed risk factors for recurrence and epidemiological characteristics of different types of recurrent patients. RESULTS: Of 1897 successfully treated tuberculosis patients, 7.4% (141/1879) developed recurrent tuberculosis. Compared with nonrecurrent tuberculosis, patients were at higher risk of recurrence in older age (adjusted odds ratio, 1.02 for each additional year; 95% CI, 1.01 to 1.03, p = 0.003), patients previously treated for tuberculosis (adjusted odds ratio = 2.22; 95% CI, 1.52 to 3.26, p < 0.001), or with bilateral cavities (adjusted odds ratio, 1.56; 95% CI, 1.05 to 2.32, p = 0.029). Among 27.0% (38/141) recurrent tuberculosis patients with successfully sequenced pairs, relapse was substantially more common than reinfection (71.1% vs 28.9%, p = 0.014). DISCUSSION: Endogenous relapse was significantly more common than exogenous reinfection in the first 2 years after treatment in eastern China. Prioritization of high-risk groups for recurrence, such as the elderly, with a previous tuberculosis diagnosis, or with bilateral cavities, may provide opportunities to reduce post-tuberculosis morbidity.

circFAM120B functions as a tumor suppressor in esophageal squamous cell carcinoma via the miR-661/PPM1L axis and the PKR/p38 MAPK/EMT pathway.

Extensive changes of circRNA expression underscore their essential contributions to multiple hallmarks of cancers; however, their functions and mechanisms of action in esophageal squamous cell carcinoma (ESCC) remain undetermined. Here, we adopted a three-stage approach by first screening for significantly differentially expressed circRNAs in ESCC and performing an external validation study, followed by the functional analyses. The properties of circRNAs were evaluated using Sanger sequencing, RNase R digestion, actinomycin D treatment, subcellular localization analysis, and fluorescence in situ hybridization. Target transcripts were predicted using online tools and verified by dual-luciferase, RNA immunoprecipitation, qRT-PCR, and western blot. Biotin-labeled RNA-protein pull-down, mass spectrometry, and RNA immunoprecipitation were employed to identify proteins interacting with circRNAs. Gain- and loss-of-function experiments were performed to uncover the roles of circRNAs, their target genes, and binding proteins in the proliferation, metastasis, and invasion. We observed that circFAM120B (hsa_circ_0001666) was frequently downregulated in cancer tissues and patient plasma, and its expression level was related to overall survival in ESCC patients. Overexpression of circFAM120B inhibited the proliferation, metastasis, and invasion of ESCC while silencing it enhanced malignant phenotypes. Mechanistically, circFAM120B was predominantly located in the cytoplasm, guarantying its sponging for miR-661 to restore the expression of PPM1L, a tumor suppressor. We observed that circFAM120B could reduce the stability of RNA-dependent protein kinase (PKR) by promoting its ubiquitination-dependent degradation and subsequently regulating the p38 MAPK signaling pathway, resulting in the repression of EMTs in ESCC cells. Our findings suggest that circFAM120B is a promising biomarker of ESCC, which acts as a tumor suppressor via the circFAM120B/miR-661/PPM1L axis and PKR/p38 MAPK/EMT pathway, supporting its significance as a candidate therapeutic target.

Risk factors for types of recurrent tuberculosis (reactivation versus reinfection): A global systematic review and meta-analysis.

BACKGROUND: The purpose of this meta-analysis (PROSPERO number: CRD42021243204) is to perform extensive and penetrating analyses on the risk factors associated with reactivation or reinfection. METHODS: We searched PubMed and Embase using search terms. Risk factors (including gender, length of time between first onset and recurrent diagnosis, extrapulmonary tuberculosis, sputum smear, pulmonary cavity, Beijing family strains, diabetes, HIV infection, history of imprisonment, and immigration) were analyzed. The pooled risk ratio (RR) and 95% confidence interval (CI) were calculated with STATA 15.1. Heterogeneity was evaluated by I2 and P values. RESULTS: The meta-analysis included 25 studies with a total of 1,477 recurrent patients. After subgroup analysis, sensitivity analysis, and testing for publication bias, it was concluded that time spanning less than two years (RR = 1.56, 95% CI: 1.33-1.85) was a risk factor for endogenous reactivation, whereas coinfection with HIV (RR = 0.72, 95% CI: 0.63-0.83), Beijing family genotype (RR = 0.46, 95% CI: 0.32-0.67), history of imprisonment (RR = 0.36, 95% CI: 0.16-0.81), and immigration (RR = 0.66, 95% CI: 0.53-0.82) were associated with exogenous reinfection. CONCLUSIONS: The recurrence interval is a risk factor for the endogenous reactivation of tuberculosis. Infection with Beijing family strains, coinfection with HIV, imprisonment, and immigration contribute to the risk of exogenous reinfection.

Effects of Alkyl Side Chains of Small Molecule Donors on Morphology and the Photovoltaic Property of All-Small-Molecule Solar Cells.

Unraveling the relationship between nanoscale morphology of active layers and chemical structures of organic semiconductor photovoltaic materials is crucially important for further advancing the development of all-small-molecule organic solar cells (SM-OSCs). Here, in order to delve into the effect of flexible side chains of small molecule donors on the photovoltaic properties of SM-OSCs, we synthesized two new small molecule donors substituted by different flexible alkyl chains (iso-octyl chains for SM1-EH and n-octyl chains for SM1-Oct). As a result, the two small molecules present different absorption properties, energy levels, and stacking characteristics. When blending with Y6 as an acceptor, the SM1-Oct-based SM-OSC demonstrated a higher PCE value of 11.73%, while the SM1-EH-based device presents a relatively poorer PCE value of 8.42%. In addition, the morphology analysis demonstrated that, compared with the SM1-EH:Y6 blend, the SM1-Oct:Y6 blend film displayed better molecular stacking properties with stronger multilevel diffraction and preferable phase separation, resulting in the higher hole mobility, more efficient charge separation efficiency, and better device performance. These results underline that reasonably adjusting the flexible alkyl chains of small molecule donors can be an effective approach to further advance the development of the SM-OSCs field.

Inflammation and nutrition-based biomarkers in the prognosis of oesophageal cancer: a systematic review and meta-analysis.

BACKGROUND: Accumulating literature has shown the predictive values of inflammation and nutrition-based biomarkers in the prognosis of oesophageal cancer but with inconsistent findings. METHOD: We performed a meta-analysis to systematically evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), C reactive protein-to-albumin ratio (CAR), systemic inflammation index (SII), prognostic nutritional index (PNI), Glasgow Prognostic Score (GPS) and modified Glasgow Prognostic Score (mGPS) in oesophageal cancer. The outcome indicators include the overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS). We applied pooled HR, sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the curve together with 95% CI to estimate the predictive accuracy. RESULTS: A total of 72 studies, including 22 260 patients, were included in the meta-analysis. Elevated NLR, PLR CAR, SII, GPS, mGPS and decreased LMR and PNI were associated with poor OS of oesophageal cancer. A high level of NLR, PLR and GPS was related to poor DFS. A high level of NLR and GPS was related to poor CSS. The summarised AUC of CAR (0.72, 95% CI: 0.68 to 0.75) and mGPS (0.75, 95% CI: 0.71 to 0.78) surpassed any other indicators. CONCLUSIONS: Clinical indicators such as NLR, PLR, LMR, PNI, SII, CAR, GPS and mGPS have the moderate predictive ability in OS, DFS and CSS of oesophageal cancer. The pretreatment level of CAR and mGPS showed an outstanding prediction value in 5-year OS for oesophageal cancer.

A Prospective Cohort Study on the Prevalent and Recurrent Tuberculosis Isolates Using the MIRU-VNTR Typing.

The study aims to describe the clustering characteristics of Mycobacterium tuberculosis (M.tb) strains circulating in eastern China and determine the ratio of relapse and reinfection in recurrent patients. We recruited sputum smear-positive pulmonary tuberculosis cases from five cities of Jiangsu Province, China, during August 2013 and December 2015. Patients were followed for the treatment outcomes and recurrence based on a cohort design. M.tb strains were isolated and genotyped using the 12-locus MIRU-VNTR. The Beijing family was identified by the extended Region of Difference (RD) analysis. The Hunter-Gaston Discriminatory Index (HGDI) was used to judge the resolution ability of MIRU-VNTR. The odds ratio (OR) together with 95% confidence interval (CI) were used to estimate the strength of association. We performed a cluster analysis on 2098 M.tb isolates and classified them into 545 genotypes and five categories (I, 0.19%; II, 0.43%; III, 3.34%; IV, 77.46%; V, 18.59%). After adjusting for potential confounders, the Beijing family genotype (OR = 118.63, 95% CI: 79.61-176.79, P = 0.001) was significantly related to the dominant strain infections. Patients infected with non-dominant strains had a higher risk of the pulmonary cavity (OR = 1.39, 95% CI: 1.01-1.91, P = 0.046). Among 37 paired recurrent cases, 22 (59.46%) were determined as endogenous reactivation, and 15 (40.54%) were exogenous reinfection. The type of M.tb strains prevalent in Jiangsu Province is relatively single. Beijing family strains infection is dominant in local tuberculosis cases. Endogenous reactivation appears to be a major cause of recurrent tuberculosis in Eastern China. This finding emphasizes the importance of case follow-up and monitoring after the completion of antituberculosis treatment.

Photoinduced-reset and multilevel storage transistor memories based on antimony-doped tin oxide nanoparticles floating gate.

Recently, antimony-doped tin oxide nanoparticles (ATO NPs) have been widely used in the fields of electronics, photonics, photovoltaics, sensing, and other fields because of their good conductivity, easy synthesis, excellent chemical stability, high mechanical strength, good dispersion and low cost. Herein, for the first time, a novel nonvolatile transistor memory device is fabricated using ATO NPs as charge trapping sites to enhance the memory performance. The resulting organic nano-floating gate memory (NFGM) device exhibits outstanding memory properties, including tremendous memory window (∼85 V), superhigh memory on/off ratio (∼109), long data retention (over 10 years) and eminent multilevel storage behavior, which are among the optimal performances in NFGM devices based on organic field effect transistors. Additionally, the device displays photoinduced-reset characteristic with low energy consumption erasing operation. This study provides novel avenues for the manufacture of simple and low-cost data storage devices with outstanding memory performance, multilevel storage behavior and suitability as platforms for integrated circuits.

Fine-Tuning Miscibility and π-π Stacking by Alkylthio Side Chains of Donor Molecules Enables High-Performance All-Small-Molecule Organic Solar Cells.

Optimization of morphology and precise control of miscibility between donors and acceptors play an important role in improving the power conversion efficiencies (PCEs) of all-small-molecule organic solar cells (SM-OSCs). Besides device optimization, methods such as additives and thermal annealing are applied for finely tuning bulk-heterojunction morphology; strategies of molecular design are also the key to achieve efficient phase separation. Here, a series of A-D-A-type small-molecule donors (SM4, SM8, and SM12) based on benzodithiophene units were synthesized with different lengths of alkylthio side chains to regulate crystallinity, and their miscibility with the acceptor (BO-4Cl) was investigated. Consequently, SM4 with a short alkylthio substituent had a high crystallization propensity, leading to the oversized molecular domains and the poor morphology of the active layer. Meanwhile, SM12 with a longer alkylthio substituent showed weak crystallinity, causing a relatively looser π-π stacking and thus adversely affecting charge-carrier transport. The SM-OSC based on the small-molecule donor SM8 with a mid-length alkylthio substituent achieved a better PCE over 13%, which was attributed to a more harmonious blend miscibility without sacrificing carrier-charge transport. Eventually, the modulation of phase separation and miscibility via controlling the lateral side chains has proven its potential in optimizing the blend morphology to aid the development of highly efficient SM-OSCs.

A Quinoxaline-Based D-A Copolymer Donor Achieving 17.62% Efficiency of Organic Solar Cells.

Side-chain engineering has been an effective strategy in tuning electronic energy levels, intermolecular interaction, and aggregation morphology of organic photovoltaic materials, which is very important for improving the power conversion efficiency (PCE) of organic solar cells (OSCs). In this work, two D-A copolymers, PBQ5 and PBQ6, are designed and synthesized based on bithienyl-benzodithiophene (BDTT) as the donor (D) unit, difluoroquinoxaline (DFQ) with different side chains as the acceptor (A) unit, and thiophene as the π-bridges. PBQ6 with two alkyl-substituted fluorothiophene side chains on the DFQ units possesses redshifted absorption, stronger intermolecular interaction, and higher hole mobility than PBQ5 with two alkyl side chains on the DFQ units. The blend film of the PBQ6 donor with the Y6 acceptor shows higher and balanced hole/electron mobilities, less charge carrier recombination, and more favorable aggregation morphology. Therefore, the OSC based on PBQ6:Y6 achieves a PCE as high as 17.62% with a high fill factor of 77.91%, which is significantly higher than the PCE (15.55%) of the PBQ5:Y6-based OSC. The PCE of 17.62% is by far one of the highest efficiencies for the binary OSCs with polymer donor and Y6 acceptor.

TOR functions as a molecular switch connecting an iron cue with host innate defense against bacterial infection.

As both host and pathogen require iron for survival, iron is an important regulator of host-pathogen interactions. However, the molecular mechanism by which how the availability of iron modulates host innate immunity against bacterial infections remains largely unknown. Using the metazoan Caenorhabditis elegans as a model, we demonstrate that infection with a pathogenic bacterium Salmonella enterica serovar Typhimurium induces autophagy by inactivating the target of rapamycin (TOR). Although the transcripts of ftn-1 and ftn-2 encoding two H-ferritin subunits are upregulated upon S. Typhimurium infection, the ferritin protein is kept at a low level due to its degradation mediated by autophagy. Autophagy, but not ferritin, is required for defense against S. Typhimurium infection under normal circumstances. Increased abundance of iron suppresses autophagy by activating TOR, leading to an increase in the ferritin protein level. Iron sequestration, but not autophagy, becomes pivotal to protect the host from S. Typhimurium infection in the presence of exogenous iron. Our results show that TOR acts as a regulator linking iron availability with host defense against bacterial infection.

Diagnostic Performance of GeneChip for the Rapid Detection of Drug-Resistant Tuberculosis in Different Subgroups of Patients.

OBJECTIVE: Drug-resistant tuberculosis (DR-TB) is a growing problem worldwide. The rapid drug susceptibility test (DST) of DR-TB enables the timely administration of a chemotherapy regimen that effectively treats DR-TB. GeneChip has been reported as a novel molecular diagnostic tool for rapid diagnosis but has limited data on the performance of subgroup patients with DR-TB. This study aims to assess the diagnostic value of GeneChip in patients with different sexes, ages, treatment histories, treatment outcomes, and places of residence. METHODS: We recruited newly registered sputum smear-positive pulmonary TB patients from January 2011 to September 2020 in Lianyungang City, Jiangsu Province, China. We applied both GeneChip and DST to measure drug resistance to rifampin (RIF) and isoniazid (INH). The kappa value, sensitivity, specificity, and agreement rate (AR) were calculated. We also applied a Classification and Regression Tree to explore factors related to the performance of GeneChip. RESULTS: We observed that sex, age, treatment history, treatment outcomes, and drug resistance type were significantly associated with the performance of GeneChip. For RIF resistance, there was significant accordance in young patients (kappa: 0.79) and cases with the treatment failure outcome (kappa: 0.92). For multidrug resistance (MDR), there was significant accordance in young cases (kappa: 0.77). Compared with previously treated patients, the newly treated patients had a significantly higher AR in detecting RIF resistance (0.97 vs 0.92), INH resistance (0.95 vs 0.89), and MDR (0.98 vs 0.92). The overall sensitivity, specificity, AR and kappa value for the diagnosis of MDR-TB were 0.70 (95% CI: 0.63-0.70), 0.99 (95% CI: 0.98-0.99), 0.98 (95% CI: 0.97-0.98), and 0.72 (95% CI: 0.67-0.78), respectively. CONCLUSION: We observed a high concordance between GeneChip and DST among TB patients with different characteristics, indicating that GeneChip can be a potential alternative tool for rapid MDR-TB detection.

Drug resistance gene mutations and treatment outcomes in MDR-TB: A prospective study in Eastern China.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) poses a serious challenge to TB control. It is of great value to search for drug resistance mutation sites and explore the roles that they play in the diagnosis and prognosis of MDR-TB. METHODS: We consecutively enrolled MDR-TB patients from five cities in Jiangsu Province, China, between January 2013 and December 2014. Drug susceptibility tests of rifampin, isoniazid, ofloxacin, and kanamycin were routinely performed by proportion methods on Lowenstein-Jensen (LJ) medium. Drug resistance-related genes were sequenced, and the consistency of genetic mutations and phenotypic resistance was compared. The association between mutations and treatment outcomes was expressed as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 87 MDR-TB patients, 71 with treatment outcomes were involved in the analysis. The proportion of successful treatment was 50.7% (36/71). The rpoB gene exhibited the highest mutation rate (93.0%) followed by katG (70.4%), pncA (33.8%), gyrA (29.6%), eis (15.5%), rrs (12.7%), gyrB (9.9%) and rpsA (4.2%). Multivariable analysis demonstrated that patients with pncA gene mutations (adjusted OR: 19.69; 95% CI: 2.43-159.33), advanced age (adjusted OR: 13.53; 95% CI: 1.46-124.95), and nonstandard treatment (adjusted OR: 7.72; 95% CI: 1.35-44.35) had a significantly higher risk of poor treatment outcomes. CONCLUSIONS: These results suggest that Mycobacterium tuberculosis gene mutations may be related to phenotypic drug susceptibility. The pncA gene mutation along with treatment regimen and age are associated with the treatment outcomes of MDR-TB.

Silicon and oxygen synergistic effects for the discovery of new high-performance nonfullerene acceptors.

In organic electronics, an aromatic fused ring is a basic unit that provides π-electrons to construct semiconductors and governs the device performance. The main challenge in developing new π-skeletons for tuning the material properties is the limitation of the available chemical approach. Herein, we successfully synthesize two pentacyclic siloxy-bridged π-conjugated isomers to investigate the synergistic effects of Si and O atoms on the geometric and electronic influence of π-units in organic electronics. Notably, the synthesis routes for both isomers possess several advantages over the previous approaches for delivering conventional aromatic fused-rings, such as environmentally benign tin-free synthesis and few synthetic steps. To explore their potential application as photovoltaic materials, two isomeric acceptor-donor-acceptor type acceptors based on these two isomers were developed, showing a decent device efficiency of 10%, which indicates the great potential of this SiO-bridged ladder-type unit for the development of new high-performance semiconductor materials.

Evaluation of cytokines as a biomarker to distinguish active tuberculosis from latent tuberculosis infection: a diagnostic meta-analysis.

OBJECTIVES: With a marginally effective vaccine and no significant breakthroughs in new treatments, a sensitive and specific method to distinguish active tuberculosis from latent tuberculosis infection (LTBI) would allow for early diagnosis and limit the spread of the pathogen. The analysis of multiple cytokine profiles provides the possibility to differentiate the two diseases. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Cochrane Library, Clinical Key and EMBASE databases were searched on 31 December 2019. ELIGIBILITY CRITERIA: We included case-control studies, cohort studies and randomised controlled trials considering IFN-γ, TNF-α, IP-10, IL-2, IL-10, IL-12 and VEGF as biomarkers to distinguish active tuberculosis and LTBI. DATA EXTRACTION AND SYNTHESIS: Two students independently extracted data and assessed the risk of bias. Diagnostic OR, sensitivity, specificity, positive and negative likelihood ratios and area under the curve (AUC) together with 95% CI were used to estimate the diagnostic value. RESULTS: Of 1315 records identified, 14 studies were considered eligible. IL-2 had the highest sensitivity (0.84, 95% CI: 0.72 to 0.92), while VEGF had the highest specificity (0.87, 95% CI: 0.73 to 0.94). The highest AUC was observed for VEGF (0.85, 95% CI: 0.81 to 0.88), followed by IFN-γ (0.84, 95% CI: 0.80 to 0.87) and IL-2 (0.84, 95% CI: 0.81 to 0.87). CONCLUSION: Cytokines, such as IL-2, IFN-γ and VEGF, can be utilised as promising biomarkers to distinguish active tuberculosis from LTBI. PROSPERO REGISTRATION NUMBER: CRD42020170725.