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Objective: In moyamoya disease (MMD) with direct or combined revascularization, the initially hemodynamic recipient features are likely one of the main causes of acute hemodynamic disruption. Previous studies have explored the relationship between recipient diameter or flow velocity and postoperative complications, but there are still no optimal selection criteria with multiple potential recipient vessels. Cerebral edema is one of the most common radiological manifestations in the acute postoperative period. This study assessed the hemodynamic characteristics of cortex vessels related to postoperative cerebral edema., Methods: All patients who had undergone direct or combined revascularization with preoperative digital subtraction angiography (DSA) between 2019 and 2021 were eligible for inclusion in this study. The application of DSA was performed and regular radiological examinations were employed after surgery. DSA was analyzed with the hemodynamic features within chosen recipient vessels. Cerebral edema was identified as a low-density image on CT or high signaling in the MRI T2 phase. The recipient hemodynamic characteristics and demographic presentation, as well as clinical data, were retrospectively analyzed in this study., Results: A total of 103 patients underwent direct or combined revascularization with preoperative DSA. The mean age of this enrolled cohort was 44.31 ± 10.386 years, in which bilaterally involved MMD accounted for the main part. The preliminary correlation analysis found preoperative disease period ( p = 0.078), recipients observed in angiography ( p = 0.002), and surgery on the left ( p = 0.097) may be associated with cerebral edema. The following regression analysis confirmed low occurrence of cerebral edema was accompanied by recipients observed in angiography ( p = 0.003). After subdividing by flow direction and hemodynamic sources, the incidence rate of anterograde direction, anterior sources, and posterior sources were significantly lower than undetected recipients., Conclusions: Cerebral edema is a common radiological manifestation in MMDs after surgery. In this study, the observation in angiography reliably identifies a variety of physiological or pathological recipient detection, flow direction, and hemodynamic sources in patients with MMD after revascularization, which indicates the selection strategy of potential recipients and highlights the importance of recipient observability in DSA. Meanwhile, vascular conditions determined by recipient hemodynamics meditate the occurrence of postoperative cerebral edema., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Li, Tong, Hu, He, Fu, Zhou, Cao, Yu, Zhou, Xu and Wang.)

New particle formation in the upper free troposphere is a major global source of cloud condensation nuclei (CCN) 1-4 . However, the precursor vapours that drive the process are not well understood. With experiments performed under upper tropospheric conditions in the CERN CLOUD chamber, we show that nitric acid, sulfuric acid and ammonia form particles synergistically, at rates that are orders of magnitude faster than those from any two of the three components. The importance of this mechanism depends on the availability of ammonia, which was previously thought to be efficiently scavenged by cloud droplets during convection. However, surprisingly high concentrations of ammonia and ammonium nitrate have recently been observed in the upper troposphere over the Asian monsoon region 5,6 . Once particles have formed, co-condensation of ammonia and abundant nitric acid alone is sufficient to drive rapid growth to CCN sizes with only trace sulfate. Moreover, our measurements show that these CCN are also highly efficient ice nucleating particles-comparable to desert dust. Our model simulations confirm that ammonia is efficiently convected aloft during the Asian monsoon, driving rapid, multi-acid HNO 3 -H 2 SO 4 -NH 3 nucleation in the upper troposphere and producing ice nucleating particles that spread across the mid-latitude Northern Hemisphere., (© 2022. The Author(s).)

Overcoming the lack of drugs for the treatment of traumatic brain injury (TBI) has long been a major challenge for the pharmaceutical industry. MiRNAs have emerged as potential targets for progress assessment and intervention against TBI. The brain-enriched miRNA let-7i has been proposed as an ideal candidate biomarker for TBI, but its regulatory roles in brain injury remain largely unknown. Here, we find that the expression of let-7i is significantly downregulated in the early stages of a hippocampal stab wound injury. The noninvasive intranasal administration of let-7i agomir significantly improves cognitive function and suppresses neuroinflammation, glial scar formation, and neuronal apoptosis in TBI mice. Mechanically, STING is a direct downstream target of let-7i after brain injury. Furthermore, the intranasal delivery of let-7i agomir can also effectively inhibit STING and is beneficial for inflammation resolution and neuronal survival in a mouse model of pial vessel disruption stroke. Consequently, let-7i agomir is a promising candidate for clinical application as a chemically engineered oligonucleotides-based therapeutic for brain injury.

Intense new particle formation events are regularly observed under highly polluted conditions, despite the high loss rates of nucleated clusters. Higher than expected cluster survival probability implies either ineffective scavenging by pre-existing particles or missing growth mechanisms. Here we present experiments performed in the CLOUD chamber at CERN showing particle formation from a mixture of anthropogenic vapours, under condensation sinks typical of haze conditions, up to 0.1 s -1 . We find that new particle formation rates substantially decrease at higher concentrations of pre-existing particles, demonstrating experimentally for the first time that molecular clusters are efficiently scavenged by larger sized particles. Additionally, we demonstrate that in the presence of supersaturated gas-phase nitric acid (HNO 3 ) and ammonia (NH 3 ), freshly nucleated particles can grow extremely rapidly, maintaining a high particle number concentration, even in the presence of a high condensation sink. Such high growth rates may explain the high survival probability of freshly formed particles under haze conditions. We identify under what typical urban conditions HNO 3 and NH 3 can be expected to contribute to particle survival during haze., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Herein, a tunable iodization/deuterolysis protocol for phosphonium ylides by employing D 2 O as the deuterium source was designed. Notably, this process could be manipulated by tuning the base, thus leading to two valuable deuterated building blocks - benzyl iodides and aromatic aldehydes with broad substrate scope, good functional group compatibility and excellent deuteration degree. Concise syntheses of a series of deuterated drug analogues have been achieved based on the developed deuteration reaction platform.

Heterogeneous uptake of hypoiodous acid (HOI), the dominant inorganic iodine species in the marine boundary layer (MBL), on sea-salt aerosol (SSA) to form iodine monobromide and iodine monochloride has been adopted in models with assumed efficiency. Recently, field measurements have reported a much faster rate of this recycling process than previously assumed in models. Here, we conduct global model simulations to quantify the range of effects of iodine recycling within the MBL, using Conventional, Updated, and Upper-limit coefficients. When considering the Updated coefficient, iodine recycling significantly enhances gaseous inorganic iodine abundance (∼40%), increases halogen atom production rates (∼40% in I, >100% in Br, and ∼60% in Cl), and reduces oxidant levels (-7% in O 3 , -2% in OH, and -4% in HO 2 ) compared to the simulation without the process. We appeal for further direct measurements of iodine species, laboratory experiments on the controlling factors, and multiscale simulations of iodine heterogeneous recycling., (© 2022. The Authors.)

A phosphine-mediated, well-designed Morita-Baylis-Hillman-type/Wittig cascade for the rapid assembly of a quinolinone framework from benzaldehyde derivatives is developed for the first time. By rationally combining I 2 /NIS-mediated cyclization, biologically relevant 3-(benzopyrrole/furan-2-yl) quinolinones were facilely synthesized in a one-pot process by starting from 3-styryl-quinolinones bearing an o -hydroxy/amino group, significantly expanding the chemical space of this privileged skeleton. Further utility of this protocol is illustrated by successfully performing this transformation in a catalytic manner through in situ reduction of phosphine oxide by phenylsilane.

The understanding at a molecular level of ambient secondary organic aerosol (SOA) formation is hampered by poorly constrained formation mechanisms and insufficient analytical methods. Especially in developing countries, SOA related haze is a great concern due to its significant effects on climate and human health. We present simultaneous measurements of gas-phase volatile organic compounds (VOCs), oxygenated organic molecules (OOMs), and particle-phase SOA in Beijing. We show that condensation of the measured OOMs explains 26-39% of the organic aerosol mass growth, with the contribution of OOMs to SOA enhanced during severe haze episodes. Our novel results provide a quantitative molecular connection from anthropogenic emissions to condensable organic oxidation product vapors, their concentration in particle-phase SOA, and ultimately to haze formation.

Based on ITS sequences, the molecular identification of Cordyceps cicadae and Tolypocladium dujiaolongae was carried out, and high-performance liquid chromatography(HPLC) fingerprint combined with chemical pattern recognition method was established to differentiate C. cicadae from its adulterant T. dujiaolongae. The genomic DNA from 10 batches of C. cicadae and five batches of T. dujiaolongae was extracted, and ITS sequences were amplified by PCR and sequenced. The stable differential sites of these two species were compared and the phylogenetic tree was constructed via MEGA 7.0. HPLC was used to establish the fingerprints of C. cicadae and T. dujiaolongae, and similarity evaluation, cluster analysis(CA), principal component analysis(PCA), and partial least squares discriminant analysis(PLS-DA) were applied to investigate the chemical pattern recognition. The result showed that the sources of these two species were different, and there were 115 stable differential sites in ITS sequences of C. cicadae and T. dujiao-longae. The phylogenetic tree could distinguish them effectively. HPLC fingerprints of 18 batches of C. cicadae and 5 batches of T. dujiaolongae were established. The results of CA, PCA, and PLS-DA were consistent, which could distinguish them well, indicating that there were great differences in chemical components between C. cicadae and T. dujiaolongae. The results of PLS-DA showed that six components such as uridine, guanosine, adenosine, and N~6-(2-hydroxyethyl) adenosine were the main differential markers of the two species. ITS sequences and HPLC fingerprint combined with the chemical pattern recognition method can serve as the identification and differentiation methods for C. cicadae and T. dujiaolongae.

Background: In accordance with increasing studies, long non-coding RNAs (LncRNAs) act pivotally in the occurrence as well as development of several human diseases. But how lncRNA SNHG12 acts in osteoarthritis (OA) is still not clear., Methods: We applied CCK-8 to determine cell viability, along with qRT-PCR to detect mRNA expression. Using luciferase reporter experiment, our team detected the binding relationship between lncRNA SNHG12 along with miR-16-5p., Results: The inflammatory factor IL-1β induced chondrocytes to express lncRNA SNHG12, and lncRNA SNHG12 expression was up-regulated in OA tissues. Additionally, our personnel proved that IL-1β inhibited miR-16-5p expression in chondrocytes, which in OA tissues was lower than that in normal tissues. miR-16-5p expression level in the OA patients' tissue was negatively correlated with lncRNA SNHG12 expression. The high-expression lncRNA SNHG12 inhibits chondrocyte proliferation, promoting apoptosis and inflammation as well as extracellular matrix (ECM) degradation. These effects can be reversed by co-transfecting miR-16-5p mimic. In addition, our work revealed that miR-16-5p is a target of lncRNA SNHG12., Conclusions: lncRNA SNHG12 regulates OA development by inhibiting miR-16-5p expression in chondrocytes. We believe that the lncRNA SNHG12/miR-16-5p axis might be a potential therapeutic and diagnostic target for OA.

Transcription factor Broad Complex (BR-C) is an ecdysone primary response gene in insects and participates in the regulation of insect growth and development. In this study, we performed a genome-wide identification of BR-C target genes in silkworm (Bombyx mori) using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). As a result, a total of 1006 BR-C ChIP peaks were identified, and 15% of peaks were located in the promoter regions of 133 protein-coding genes. Functional annotation revealed that these ChIP peak-associated genes, as potential BR-C targets, were enriched in pathways related to biosynthetic process, metabolic process, and development. Transcriptome analysis and quantitative real-time polymerase chain reaction (PCR) examination revealed that developmental changes in expression patterns of a portion of potential BR-C targets, including HR96 and GC-α1, were similar to those of BR-C. ChIP-PCR examination confirmed that BR-C could directly bind to the promoters of potential targets. Further, dual luciferase assays demonstrated that HR96 promoter activity was significantly upregulated following BR-C overexpression, and this upregulation was abolished when the binding motif in the promoter was truncated. This study will be helpful for deciphering the regulatory roles of BR-C during insect growth and development., (© 2020 Institute of Zoology, Chinese Academy of Sciences.)

Objective: This study examined the association between iron status and a set of breast cancer risk factors among U.S. adult women aged 20-80 years., Methods: Data from National Health and Nutrition Examination Survey (2017-2018) were used to examine the relation between serum ferritin, serum iron and transferrin saturation with a set of breast cancer risk factors [body mass index (BMI), waist circumference, glycosylated hemoglobin (HbA1c), fasting plasma glucose, insulin and HOMA-IR]. The multivariable linear regressions were used controlling for age, race/ethnicity, menopause status, education level, smoking status, alcohol consumption, physical activity, high-sensitivity C-reactive protein (hsCRP) and total energy intake., Results: HbA1c, BMI and waist circumference data were available for 1902 women with a fasting sample (n = 913) for fasting plasma glucose, insulin and HOMA-IR. Transferrin saturation had significant, inverse associations with BMI, waist circumference and HbA1c. The size of difference observed were that participants in the fourth quartile of transferrin saturation had a 4.50 kg/m 2 smaller BMI, a 9.36 cm smaller waist circumference and a 0.1 % lower HbA1c level than participants in the first quartile. Similarly, serum iron concentrations were inversely associated with BMI and waist circumference. In addition, serum iron had significant, inverse associations with insulin and HOMA-IR. Sensitivity analyses among men gave similar results. For serum ferritin, there was a trend towards a positive association between waist circumference, HbA1c and fasting plasma glucose with serum ferritin. However, the associations did not reach statistical significance among women., Conclusions: Iron status may impact breast cancer risk via effects on adiposity or glucose metabolism. The findings should be confirmed with further prospective data., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Background: There is an urgent need to identify potential targets in anticancer therapy to improve the survival and prognosis of patients with ovarian cancer (OC). Herein, we investigated the functional significance of chemokine (C-X-C motif) ligand 14 (CXCL14) in OC cell growth and epithelial-mesenchymal transition (EMT)., Methods: qRT PCR and western blotting was used to detect CXCL14 mRNA level and protein expression, respectively. The functional mechanism of CXCL14 in OC was investigated by CCK-8, colony formation and transwell assays. The migration ability of OC cell was determined using wound healing. The protein expressions of CXCL14 and β-catenin in OC tissues were determined by immumohistochemical staining., Results: We demonstrated that high levels of CXCL14 were associated with a worse prognosis in patients with OC. CXCL14 knockdown considerably restrained the growth, migration and invasion of OC cell in vitro. In contrast, ectopic CXCL14 overexpression yielded the opposite results. Investigations to determine the underlying molecular mechanisms revealed that the Wnt/β-catenin signaling pathway is involved in CXCL14-facilitated OC cell invasiveness., Conclusion: These data collectively demonstrate that CXCL14 contributes to OC cell growth and metastatic potential by regulating the Wnt/β-catenin signaling pathway., (© 2021. The Author(s).)

Objective: To compare the value of 25-hydroxyvitamin D3 (25-(OH)D3) with other clinical parameters in the prediction and diagnosis of eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). Methods: Eligible chronic rhinosinusitis with nasal polyps (CRSwNP) patients and healthy subjects in the Affiliated Hospital of Guizhou Medical University from January to April of 2021 were included for this study. The age, gender, past history and other basic characteristics of all subjects were recorded. The CRSwNP patients were classified into ECRSwNP and non-eosinophilic chronic rhinosinusitis with nasal polyps (nECRSwNP) endotypes by the percentage of tissue eosinophils. Serum 25-(OH)D3 levels measurements were performed in all subjects. Paranasal sinus CT scans, blood eosinophil counts, and determination of total immunoglobulin E (total IgE), Th1/Th2 plasma cytokines and nasal nitric oxide (nNO) levels were performed before surgery. Logistic regression analysis was used to evaluate the related factors of ECRSwNP. Receiver operating characteristic (ROC) curves was used to evaluate the predictive potential of the clinical parameters. Results: One hundred and twenty-seven CRSwNP patients and 40 healthy subjects were recruited, including 74 males and 93 females of the patients, with the age of (38.73±13.05) years. In patients with ECRSwNP, serum 25-(OH)D3 levels were significantly lower than those in nECRSwNP patients ((26.14±4.58) ng/ml vs (35.71±7.86) ng/ml, t =-8.564, P <0.01). The prevalence of asthma, prevalence of allergic rhinitis, peripheral blood eosinophil counts, total IgE levels, nNO levels and CT scores ratio for ethmoid sinus and maxillary sinus (E/M ratio) of ECRSwNP patients were significantly higher than those in nECRSwNP patients (all P <0.05). However, there was no significant difference in Th1/Th2 cytokines levels between the histological types of CRSwNP (all P >0.05). Among the predictive indicators, 25-(OH)D3 had the highest predictive value, with ROC area under curve (AUC) value of 0.882. The best cut-off point of 28.5 ng/ml for 25-(OH)D3 demonstrated a sensitivity of 0.871 and a specificity of 0.762 for ECRSwNP. Conclusion: Measurement of serum 25-(OH)D3 level may be used as an effective method to distinguish between ECRSwNP and nECRSwNP.

A novel phosphine-catalysed, one-pot domino approach for the annulation of 2-formylphenyl alkynoates with activated methylene compounds to construct various cyclopentene-fused dihydrocoumarins is reported. This developed strategy provides a facile and efficient approach for the synthesis of structurally complex coumarins from inexpensive and readily available alkynoates.

Aerosol particles negatively affect human health while also having climatic relevance due to, for example, their ability to act as cloud condensation nuclei. Ultrafine particles (diameter D p < 100 nm) typically comprise the largest fraction of the total number concentration, however, their chemical characterization is difficult because of their low mass. Using an extractive electrospray time-of-flight mass spectrometer (EESI-TOF), we characterize the molecular composition of freshly nucleated particles from naphthalene and β-caryophyllene oxidation products at the CLOUD chamber at CERN. We perform a detailed intercomparison of the organic aerosol chemical composition measured by the EESI-TOF and an iodide adduct chemical ionization mass spectrometer equipped with a filter inlet for gases and aerosols (FIGAERO-I-CIMS). We also use an aerosol growth model based on the condensation of organic vapors to show that the chemical composition measured by the EESI-TOF is consistent with the expected condensed oxidation products. This agreement could be further improved by constraining the EESI-TOF compound-specific sensitivity or considering condensed-phase processes. Our results show that the EESI-TOF can obtain the chemical composition of particles as small as 20 nm in diameter with mass loadings as low as hundreds of ng m -3 in real time. This was until now difficult to achieve, as other online instruments are often limited by size cutoffs, ionization/thermal fragmentation and/or semi-continuous sampling. Using real-time simultaneous gas- and particle-phase data, we discuss the condensation of naphthalene oxidation products on a molecular level., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

CD63 is a member of the four-transmembrane-domain protein superfamily and is the first characterized tetraspanin protein. In the present study, we cloned the common carp (Cyprinus Carpio) CD63 (ccCD63) sequence and found that the ccCD63 ORF contained 711 bp and encoded a protein of 236 amino acids. Homology analysis revealed that the complete ccCD63 sequence had 84.08% amino acid similarity to CD63 of Sinocyclocheilus anshuiensis. Subcellular localization analysis revealed that ccCD63 was localized in the cytoplasm. Quantitative real-time PCR (qRT-PCR) analysis indicated that ccCD63 was expressed in the gill, intestine, liver, spleen, brain and kidney, with higher expression in spleen and brain tissues than in the other examined tissues. After koi herpesvirus (KHV) infection, these tissues exhibited various expression levels of ccCD63. The expression level was the lowest in the liver and highest in the brain; the expression level in the brain was 8.7-fold higher than that in the liver. Furthermore, knockdown of ccCD63 promoted KHV infection. Moreover, ccCD63 was correlated with the regulation of RIG-I/MAVS/TRAF3/TBK1/IRF3 and may be involved in the antiviral response through the RIG-I viral recognition signalling pathway in a TRAF3/TBK1-dependent manner. Taken together, our results suggested that ccCD63 upregulated the interaction of KHV with the host immune system and suppressed the dissemination of KHV., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Neurotrauma has been recognized as a risk factor for neurodegenerative diseases, and sex difference of the incidence and outcome of neurodegenerative diseases has long been recognized. Past studies suggest that microglia could play a versatile role in both health and disease. So far, the microglial mechanisms underlying neurodegeneration and potentially lead to sex-specific therapies are still very open. Here we applied whole transcriptome analysis of microglia acutely isolated at different timepoints after a cortical stab wound injury to gain insight into genes that might be dysregulated and transcriptionally different between males and females after cortical injury. We found that microglia displayed distinct temporal and sexual molecular signatures of transcriptome after cortical injury. Hypotheses and gene candidates that we presented in the present study could be worthy to be examined to explore the roles of microglia in neurotrauma and in sex-biased neurodegenerative diseases., (© 2021 Wiley Periodicals LLC.)

Compounds bearing fluorinated moieties are pervasive in a wide range of pharmaceuticals and agrochemicals. The installation of fluorinated units is a persistently vital task in synthetic chemistry, where facile and manipulable assays are highly demanding. Herein, we establish a general and programmable fluorination strategy for the modular assembly of mono- and difluoromethylarenes through the controllable deprotonation and fluorination of phosphonium ylides. Moreover, the rational combination of the reaction sequence allows the rapid construction of diversified fluorine-containing arenes.

Background: Burns cause a huge economic burden to society, and the wounds can be very difficult to manage. Clinical experience suggests that amniotic membrane (AM) is an economical and effective biological dressing for burns. However, few systematic reviews or meta-analyses have been published on such use. We aimed to evaluate the role of AM dressings in burn wounds., Methods: A systematic search of the PubMed, Cochrane, Embase, and Web of Science databases was conducted in March 2020. The search was conducted to identify randomized control trials that compared selected features of AM with those of other dressings, such as silver sulfadiazine, polyurethane membrane, and honey. For skin-grafted wounds, we compared AM-covered skin grafts and traditional staple-fixed skin grafts. Outcomes of interest for the efficacy analysis included wound infection, pain, itching, scarring, and healing time. The number of adverse events in each treatment group, the rate of withdrawal because of adverse effects, the cost of treatment, and patient acceptability were assessed for the feasibility analysis., Results: Eleven randomized controlled trials with 816 participants total were identified in our review. Amniotic membrane treatment was more effective than conventional methods, silver sulfadiazine, and polyurethane membrane in treating burn wounds, but AM appears to be less effective than honey. No reports of AM-related disease transmission or adverse reactions were described in the included articles., Conclusion: Amniotic membrane has beneficial effects in treating burn wounds; however, the evidence needs to be strengthened by further robust randomized controlled trials., Level of Evidence: Systematic Review/Meta-analysis, level III., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Iodic acid (HIO 3 ) is known to form aerosol particles in coastal marine regions, but predicted nucleation and growth rates are lacking. Using the CERN CLOUD (Cosmics Leaving Outdoor Droplets) chamber, we find that the nucleation rates of HIO 3 particles are rapid, even exceeding sulfuric acid-ammonia rates under similar conditions. We also find that ion-induced nucleation involves IO 3 - and the sequential addition of HIO 3 and that it proceeds at the kinetic limit below +10°C. In contrast, neutral nucleation involves the repeated sequential addition of iodous acid (HIO 2 ) followed by HIO 3 , showing that HIO 2 plays a key stabilizing role. Freshly formed particles are composed almost entirely of HIO 3 , which drives rapid particle growth at the kinetic limit. Our measurements indicate that iodine oxoacid particle formation can compete with sulfuric acid in pristine regions of the atmosphere., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Reactive iodine plays a key role in determining the oxidation capacity, or cleansing capacity, of the atmosphere in addition to being implicated in the formation of new particles in the marine boundary layer. The postulation that heterogeneous cycling of reactive iodine on aerosols may significantly influence the lifetime of ozone in the troposphere not only remains poorly understood but also heretofore has never been observed or quantified in the field. Here, we report direct ambient observations of hypoiodous acid (HOI) and heterogeneous recycling of interhalogen product species (i.e., iodine monochloride [ICl] and iodine monobromide [IBr]) in a midlatitude coastal environment. Significant levels of ICl and IBr with mean daily maxima of 4.3 and 3.0 parts per trillion by volume (1-min average), respectively, have been observed throughout the campaign. We show that the heterogeneous reaction of HOI on marine aerosol and subsequent production of iodine interhalogens are much faster than previously thought. These results indicate that the fast formation of iodine interhalogens, together with their rapid photolysis, results in more efficient recycling of atomic iodine than currently considered in models. Photolysis of the observed ICl and IBr leads to a 32% increase in the daytime average of atomic iodine production rate, thereby enhancing the average daytime iodine-catalyzed ozone loss rate by 10 to 20%. Our findings provide direct field evidence that the autocatalytic mechanism of iodine release from marine aerosol is important in the atmosphere and can have significant impacts on atmospheric oxidation capacity., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Secondary aerosol formation in the aging process of primary emission is the main reason for haze pollution in eastern China. Pollution evolution with photochemical age was studied for the first time at a comprehensive field observation station during winter in Beijing. The photochemical age was used as an estimate of the timescale attributed to the aging process and was estimated from the ratio of toluene to benzene in this study. A low photochemical age indicates a fresh emission. The photochemical age of air masses during new particle formation (NPF) days was lower than that on haze days. In general, the strongest NPF events, along with a peak of the formation rate of 1.5 nm (J 1.5 ) and 3 nm particles (J 3 ), were observed when the photochemical age was between 12 and 24 h while rarely took place with photochemical ages less than 12 h. When photochemical age was larger than 48 h, haze occurred and NPF was suppressed. The sources and sinks of nanoparticles had distinct relation with the photochemical age. Our results show that the condensation sink (CS) showed a valley with photochemical ages ranging from 12 to 24 h, while H 2 SO 4 concentration showed no obvious trend with the photochemical age. The high concentrations of precursor vapours within an air mass lead to persistent nucleation with photochemical age ranging from 12 to 48 h in winter. Coincidently, the fast increase of PM 2.5 mass was also observed during this range of photochemical age. Noteworthy, CS increased with the photochemical age on NPF days only, which is the likely reason for the observation that the PM 2.5 mass increased faster with photochemical age on NPF days compared with other days. The evolution of particles with the photochemical age provides new insights into understanding how particles originating from NPF transform to haze pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Traumatic brain injury is a global leading cause of disability and death, which puts patients at high risk for developing dementia. Early intervention is believed as the key to minimize the development of brain damages that could aggravate the symptoms. Here, we report that the serine protease inhibitor SerpinA3N is upregulated in hippocampal neurons in the early stage of hippocampal stab injury (HSI), while its deficiency causes a greater degree of neuronal apoptosis and severer impairments of spatial learning and memory in mice after HSI. We further show that MMP2 is a key substrate of SerpinA3N, and MMP2 specific inhibitor (ARP100) can protect against neuronal apoptosis and cognitive dysfunction in mice after HSI. These findings demonstrate a critical role for SerpinA3N in neuroprotection, suggesting that SerpinA3N and MMP2 inhibitors might be a novel therapeutic agents for neurotrauma., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Mouse embryonic stem cells (ESCs) cultured in defined medium resemble the pre-implantation epiblast in the ground state, with full developmental capacity including the germline. β-Catenin is required to maintain ground state pluripotency in mouse ESCs, but its exact role is controversial. Here, we reveal a Tcf3-independent role of β-catenin in restraining germline and somatic lineage differentiation genes. We show that β-catenin binds target genes with E2F6 and forms a complex with E2F6 and HMGA2 or E2F6 and HP1γ. Our data indicate that these complexes help β-catenin restrain and fine-tune germ cell and neural developmental potential. Overall, our data reveal a previously unappreciated role of β-catenin in preserving lineage differentiation integrity in ground state ESCs., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the mental state and quality of life in patients with vasomotor rhinitis (VMR) before and after treatment, and to provide guidance for improving the overall health of VMR patients. Methods: Two hundred and twenty VMR patients (VMR group, 118 males, 102 females; aged from 18 to 72 years old), three hundred and twenty allergic rhinitis (AR) patients (AR group, 178 males, 142 females; aged from 18 to 79 years old) from January 2016 to September 2019 were selected in the otolaryngology clinic of Affiliated Hospital of Guizhou Medical University, four hundred and twenty-three healthy people (control group, 243 males, 180 females; aged from 19 to 70 years old) were selected in physical examination center at the same time by continuous enrollment method, symptom check list (SCL-90), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to evaluate the mental state of VMR patients before and after treatment, and 12-item short form health survey version 2.0 (SF-12v2) was used to evaluate their quality of life, statistical data were collected and analyzed by ANOVA and t -test. Results: The scores of eight factors (physical function, role physical function, general health, vitality, role-emotional, mental health) of SF-12v2 in VMR patients before treatment were lower than that of posttreatment, that of AR patients and the control group, the differences were significant (all P< 0.05), the scores of somatization, obsession, depression, anxiety and psychosis in SCL-90 in VMR patients before treatment were significantly higher than that of posttreatment, that of AR patients and the control group (all P< 0.05), the SAS and SDS in VMR patients before treatment (51.28±16.32; 53.28±18.55) were significantly higher than that of posttreatment (38.53±13.21; 39.35±13.34), that of AR patients (42.23±14.32; 43.32±13.78) and the control group (29.78±10.07;33.46±10.55; t (SAS) were 9.007, 6.813 and 20.59; t (SDS) were 9.043, 7.154 and 17.260, all P< 0.05). Conclusion: VMR patients generally suffer from psychological damage, which seriously affects the quality of life of the patients. On the basis of routine treatment, we should attach more importance to the negative psychology of VMR patients and intervene when necessary.

To better understand the role of aromatic hydrocarbons in new-particle formation, we measured the particle-phase abundance and volatility of oxidation products following the reaction of aromatic hydrocarbons with OH radicals. For this we used thermal desorption in an iodide-adduct Time-of-Flight Chemical-Ionization Mass Spectrometer equipped with a Filter Inlet for Gases and AEROsols (FIGAERO-ToF-CIMS). The particle-phase volatility measurements confirm that oxidation products of toluene and naphthalene can contribute to the initial growth of newly formed particles. Toluene-derived (C 7 ) oxidation products have a similar volatility distribution to that of α-pinene-derived (C 10 ) oxidation products, while naphthalene-derived (C 10 ) oxidation products are much less volatile than those from toluene or α-pinene; they are thus stronger contributors to growth. Rapid progression through multiple generations of oxidation is more pronounced in toluene and naphthalene than in α-pinene, resulting in more oxidation but also favoring functional groups with much lower volatility per added oxygen atom, such as hydroxyl and carboxylic groups instead of hydroperoxide groups. Under conditions typical of polluted urban settings, naphthalene may well contribute to nucleation and the growth of the smallest particles, whereas the more abundant alkyl benzenes may overtake naphthalene once the particles have grown beyond the point where the Kelvin effect strongly influences the condensation driving force.

Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt-β-catenin and PI3K-Akt pathways cooperate to promote tumorigenesis and resistance to therapy. In a mouse model in which both pathways are activated in stem and progenitor cells, LSCs expanded under chemotherapy-induced stress. Since Akt can activate β-catenin, inhibiting this interaction might target therapy-resistant LSCs. High-throughput screening identified doxorubicin (DXR) as an inhibitor of the Akt-β-catenin interaction at low doses. Here we repurposed DXR as a targeted inhibitor rather than a broadly cytotoxic chemotherapy. Targeted DXR reduced Akt-activated β-catenin levels in chemoresistant LSCs and reduced LSC tumorigenic activity. Mechanistically, β-catenin binds multiple immune-checkpoint gene loci, and targeted DXR treatment inhibited expression of multiple immune checkpoints specifically in LSCs, including PD-L1, TIM3 and CD24. Overall, LSCs exhibit distinct properties of immune resistance that are reduced by inhibiting Akt-activated β-catenin. These findings suggest a strategy for overcoming cancer therapy resistance and immune escape.

A list of authors and their affiliations appears at the end of the paper New-particle formation is a major contributor to urban smog 1,2 , but how it occurs in cities is often puzzling 3 . If the growth rates of urban particles are similar to those found in cleaner environments (1-10 nanometres per hour), then existing understanding suggests that new urban particles should be rapidly scavenged by the high concentration of pre-existing particles. Here we show, through experiments performed under atmospheric conditions in the CLOUD chamber at CERN, that below about +5 degrees Celsius, nitric acid and ammonia vapours can condense onto freshly nucleated particles as small as a few nanometres in diameter. Moreover, when it is cold enough (below -15 degrees Celsius), nitric acid and ammonia can nucleate directly through an acid-base stabilization mechanism to form ammonium nitrate particles. Given that these vapours are often one thousand times more abundant than sulfuric acid, the resulting particle growth rates can be extremely high, reaching well above 100 nanometres per hour. However, these high growth rates require the gas-particle ammonium nitrate system to be out of equilibrium in order to sustain gas-phase supersaturations. In view of the strong temperature dependence that we measure for the gas-phase supersaturations, we expect such transient conditions to occur in inhomogeneous urban settings, especially in wintertime, driven by vertical mixing and by strong local sources such as traffic. Even though rapid growth from nitric acid and ammonia condensation may last for only a few minutes, it is nonetheless fast enough to shepherd freshly nucleated particles through the smallest size range where they are most vulnerable to scavenging loss, thus greatly increasing their survival probability. We also expect nitric acid and ammonia nucleation and rapid growth to be important in the relatively clean and cold upper free troposphere, where ammonia can be convected from the continental boundary layer and nitric acid is abundant from electrical storms 4,5 .

Neuropsychiatric disorders are the leading cause of mental and intellectual disabilities worldwide. Current therapies against neuropsychiatric disorders are very limited, and very little is known about the onset and development of these diseases, and their most effective treatments. MIR137 has been previously identified as a risk gene for the etiology of schizophrenia, bipolar disorder, and autism spectrum disorder. Here we generated a forebrain-specific MIR137 knockout mouse model, and provided evidence that loss of miR-137 resulted in impaired homeostasis of potassium in mouse hippocampal neurons. KCC2, a potassium-chloride co-transporter, was a direct downstream target of miR-137. The KCC2 specific antagonist VU0240551 could balance the current of potassium in miR-137 knockout neurons, and knockdown of KCC2 could ameliorate anxiety-like behavior in MIR137 cKO mice. These data suggest that KCC2 antagonists or knockdown might be beneficial to neuropsychiatric disorders due to the deficiency of miR-137.

The gastrointestinal system is arguably one of the most complicated developmental systems in a multicellular organism, as it carries out at least four major functions: digestion of food, absorption of nutrients, excretion of hormones, and defense against pathogens. Anatomically, the fetal gut has a tubular structure with an outer layer of smooth muscle derived from lateral splanchnic mesoderm and an inner lining of epithelium derived from the definitive endoderm. During morphogenesis of the gut tube, the definitive endoderm transforms into a primitive gut tube with a foregut, midgut, and hindgut. During the course of further development, the midgut gives rise to the small and proximal large intestine and the hindgut gives rise to the distal large intestine and rectum. The small intestine is subdivided into three parts: duodenum, jejunum, and ileum, whereas the large intestine is subdivided into the cecum, colon, and rectum.

In this issue of JEM, Wang et al. (https://doi.org/10.1084/jem.20191130), using a single-cell RNA-seq approach, establish an atlas of human colon, rectum, and ileum epithelial cells. Their study reveals that different regions have specialized nutrient absorption preferences, microbe defenses, and endocrine function. They also identify new markers for a variety of cell types., (© 2020 He and Li.)

Anxiety and depression are major public health concerns worldwide. Although genome-wide association studies have identified several genes robustly associated with susceptibility for these disorders, the molecular and cellular mechanisms associated with anxiety and depression is largely unknown. Reduction of microRNA-137 (miR-137) level has been implicated in the etiology of major depressive disorder. However, little is known about the in vivo impact of the loss of miR-137 on the biology of anxiety and depression. Here, we generated a forebrain-specific miR-137 knockout mouse line, and showed that miR-137 is critical for dendritic and synaptic growth in the forebrain. Mice with miR-137 loss-of-function exhibit anxiety-like behavior, and impaired spatial learning and memory. We then observe an elevated expression of EZH2 in the forebrain of miR-137 knockout mice, and provide direct evidence that knockdown of EZH2 can rescue anxious phenotypes associated with the loss of miR-137. Together our results suggest that loss of miR-137 contributes to the etiology of anxiety, and EZH2 might be a potential therapeutic target for anxiety and depressive phenotypes associated with the dysfunction of miR-137., (Copyright © 2019 Yan, Sun, Wang, Liu, Mi, Liu, Wang, He, Du, Liu and Teng.)

Paper is a widely used support for use in devices for point-of-care testing (POCT) in clinical diagnosis, food safety monitoring and environmental pollution. Paper is inexpensive, biocompatible, biodegradable and allows a sample fluid to flow by capillary force. Numerous method have been developed recently for chemical modification of papers in order to introduce different functionalities. This review (with 148 refs.) summarizes the recent progress in paper-based POCT devices. The introduction summarizes the state of the art of paper-based POCT devices and the physicochemical properties of existing unmodified materials (including cellulose, cellulose-based composites, cotton fibers, glass fibers, nitrocellulose, thread). Methods for paper modification for sample pretreatment are summarized next, with subsections on sample storage and collection, sample separation, nucleic acid extraction and sample preconcentration. Another main section covers approaches for paper modification for improving POCTs, with subsections on assays for proteins, nucleic acids, drugs, ion and organic molecules. The advantages and disadvantages of these approaches are compared. Several tables are presented that summarize the various modification techniques. A concluding section summarizes the current status, addresses challenges and gives an outlook on future perspectives of POCTs. Graphical abstract This review summarizes the progress that has been made in paper based point-of-care testing (POCT) and lateral flow assays (LFAs), quite often by using advanced nanomaterials for paper modification.

: Hematopoietic stem cells (HSCs) are a unique population of cells with the remarkable ability to replenish themselves through self-renewal and to give rise to differentiated cell lineages. Though having been discovered more than 50 years ago, and having been widely used in bone marrow transplantation to treat blood disorders including leukemia, expansion of HSCs remains an unmet task, thus affecting its more effective usage in clinical practice., Purpose of Review: The purpose of this review article is to summarize past efforts in ex-vivo HSC expansion and to compare recent advances in expanding murine and human HSCs by targeting the N-methyladenosine (mA) pathway., Recent Findings: Unlike past many efforts that mainly target single or limited pathways and often lead to lineage bias or expansion of progenitor cells or limited long-term HSCs (LT-HSCs), the blocking the degradation of mA pathway has an advantage of stabilizing hundreds of key factors required for maintaining HSCs, thus resulting in expansion of functional LT-HSCs., Summary: The new approach of targeting the mA pathway has a promising application in clinical HSC-based transplantation.

Intestinal homeostasis and regeneration are driven by intestinal stem cells (ISCs) lying in the crypt. In addition to the actively cycling ISCs that maintain daily homeostasis, accumulating evidence supports the existence of other pools of stem/progenitor cells with the capacity to repair damaged tissue and facilitate rapid restoration of intestinal integrity after injuries. Appropriate control of ISCs and other populations of intestinal epithelial cells with stem cell activity is essential for intestinal homeostasis and regeneration while their deregulation is implicated in colorectal tumorigenesis. In this review, we will summarize the recent findings about ISC identity and cellular plasticity in intestine, discuss regulatory mechanisms that control ISCs for intestinal homeostasis and regeneration, and put a particular emphasis on extrinsic niche-derived signaling and intrinsic epigenetic regulation. Moreover, we highlight several fundamental questions about the precise mechanisms conferring robust capacity for intestine to maintain physiological homeostasis and repair injuries., Competing Interests: No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed.

Regulation of hematopoietic stem cells (HSCs) by bone marrow (BM) niches has been extensively studied; however, whether and how HSC subpopulations are distinctively regulated by BM niches remain unclear. Here, we functionally distinguished reserve HSCs (rHSCs) from primed HSCs (pHSCs) based on their response to chemotherapy and examined how they are dichotomously regulated by BM niches. Both pHSCs and rHSCs supported long-term hematopoiesis in homeostasis; however, pHSCs were sensitive but rHSCs were resistant to chemotherapy. Surviving rHSCs restored the HSC pool and supported hematopoietic regeneration after chemotherapy. The rHSCs were preferentially maintained in the endosteal region that enriches N-cadherin + (N-cad + ) bone-lining cells in homeostasis and post-chemotherapy. N-cad + cells were functional bone and marrow stromal progenitor cells (BMSPCs), giving rise to osteoblasts, adipocytes, and chondrocytes in vitro and in vivo. Finally, ablation of N-cad + niche cells or deletion of SCF from N-cad + niche cells impaired rHSC maintenance during homeostasis and regeneration., (Copyright © 2018 Stowers Institute for Medical Research. Published by Elsevier Inc. All rights reserved.)

DNA damage in oocytes can cause infertility and birth defects. DNA double-strand breaks (DSBs) are highly deleterious and can substantially impair genome integrity. Homologous recombination (HR)-mediated DNA DSB repair plays dominant roles in safeguarding oocyte quantity and quality. However, little is known regarding the key players of the HR repair pathway in oocytes. Here, we identified oocyte-specific gene Ooep as a novel key component of the HR repair pathway in mouse oocytes. OOEP was required for efficient ataxia telangiectasia mutated (ATM) kinase activation and Rad51 recombinase(RAD51)focal accumulation at DNA DSBs. Ooep null oocytes were defective in DNA DSB repair and prone to apoptosis upon exogenous DNA damage insults. Moreover, Ooep null oocytes exhibited delayed meiotic maturation. Therefore, OOEP played roles in preserving oocyte quantity and quality by maintaining genome stability. Ooep expression decreased with the advance of maternal age, suggesting its involvement in maternal aging.

In the initial published version of this article, there was an inadvertent omission from the Acknowledgements that this work was supported by Stowers Institute for Medical Research (SIMR-1004) and NIH National Cancer Institute grant to University of Kansas Cancer Center (P30 CA168524). This omission does not affect the description of the results or the conclusions of this work.

Background & Aims: Defects in lysosome function and autophagy contribute to the pathogenesis of alcoholic liver disease. We investigated the mechanisms by which alcohol consumption affects these processes by evaluating the functions of transcription factor EB (TFEB), which regulates lysosomal biogenesis., Methods: We performed studies with GFP-LC3 mice, mice with liver-specific deletion of TFEB, mice with disruption of the transcription factor E3 gene (TFE3-knockout mice), mice with disruption of the Tefb and Tfe3 genes (TFEB and TFE3 double-knockout mice), and Tfeb flox/flox albumin cre-negative mice (controls). TFEB was overexpressed from adenoviral vectors or knocked down with small interfering RNAs in mouse livers. Mice were placed on diets of regular ethanol feeding plus an acute binge to induce liver damage (ethanol diet); some mice also were given injections of torin-1, an inhibitor of the kinase activity of the mechanistic target of rapamycin (mTOR). Liver tissues were collected and analyzed by immunohistochemistry, immunoblots, and quantitative real-time polymerase chain reaction to monitor lysosome biogenesis. We analyzed levels of TFEB in liver tissues from patients with alcoholic hepatitis and from healthy donors (controls) by immunohistochemistry., Results: Liver tissues from mice on the ethanol diet had lower levels of total and nuclear TFEB compared with control mice, and hepatocytes had decreased lysosome biogenesis and autophagy. Hepatocytes from mice on the ethanol diet had increased translocation of mTOR into lysosomes, resulting in increased mTOR activation. Administration of torin-1 increased liver levels of TFEB and decreased steatosis and liver injury induced by ethanol. Mice that overexpressed TFEB in the liver developed less severe ethanol-induced liver injury and had increased lysosomal biogenesis and mitochondrial bioenergetics compared with mice carrying a control vector. Mice with knockdown of TFEB and TFEB-TFE3 double-knockout mice developed more severe liver injury in response to the ethanol diet than control mice. Liver tissues from patients with alcohol-induced hepatitis had lower nuclear levels of TFEB than control tissues., Conclusions: We found that ethanol feeding plus an acute binge decreased hepatic expression of TFEB, which is required for lysosomal biogenesis and autophagy. Strategies to block mTOR activity or increase levels of TFEB might be developed to protect the liver from ethanol-induced damage., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Transplantation of hematopoietic stem cells (HSCs) from human umbilical cord blood (hUCB) holds great promise for treating a broad spectrum of hematological disorders including cancer. However, the limited number of HSCs in a single hUCB unit restricts its widespread use. Although extensive efforts have led to multiple methods for ex vivo expansion of human HSCs by targeting single molecules or pathways, it remains unknown whether it is possible to simultaneously manipulate the large number of targets essential for stem cell self-renewal. Recent studies indicate that N 6 -methyladenosine (m 6 A) modulates the expression of a group of mRNAs critical for stem cell-fate determination by influencing their stability. Among several m 6 A readers, YTHDF2 is recognized as promoting targeted mRNA decay. However, the physiological functions of YTHDF2 in adult stem cells are unknown. Here we show that following the conditional knockout (KO) of mouse Ythdf2 the numbers of functional HSC were increased without skewing lineage differentiation or leading to hematopoietic malignancies. Furthermore, knockdown (KD) of human YTHDF2 led to more than a 10-fold increase in the ex vivo expansion of hUCB HSCs, a fivefold increase in colony-forming units (CFUs), and more than an eightfold increase in functional hUCB HSCs in the secondary serial of a limiting dilution transplantation assay. Mapping of m 6 A in RNAs from mouse hematopoietic stem and progenitor cells (HSPCs) as well as from hUCB HSCs revealed its enrichment in mRNAs encoding transcription factors critical for stem cell self-renewal. These m 6 A-marked mRNAs were recognized by Ythdf2 and underwent decay. In Ythdf2 KO HSPCs and YTHDF2 KD hUCB HSCs, these mRNAs were stabilized, facilitating HSC expansion. Knocking down one of YTHDF2's key targets, Tal1 mRNA, partially rescued the phenotype. Our study provides the first demonstration of the function of YTHDF2 in adult stem cell maintenance and identifies its important role in regulating HSC ex vivo expansion by regulating the stability of multiple mRNAs critical for HSC self-renewal, thus identifying potential for future clinical applications.

Hox genes modulate the properties of hematopoietic stem cells (HSCs) and reacquired Hox expression in progenitors contributes to leukemogenesis. Here, our transcriptome and DNA methylome analyses revealed that Hoxb cluster and retinoid signaling genes are predominantly enriched in LT-HSCs, and this coordinate regulation of Hoxb expression is mediated by a retinoid-dependent cis-regulatory element, distal element RARE (DERARE). Deletion of the DERARE reduced Hoxb expression, resulting in changes to many downstream signaling pathways (e.g., non-canonical Wnt signaling) and loss of HSC self-renewal and reconstitution capacity. DNA methyltransferases mediate DNA methylation on the DERARE, leading to reduced Hoxb cluster expression. Acute myeloid leukemia patients with DNMT3A mutations exhibit DERARE hypomethylation, elevated HOXB expression, and adverse outcomes. CRISPR-Cas9-mediated specific DNA methylation at DERARE attenuated HOXB expression and alleviated leukemogenesis. Collectively, these findings demonstrate pivotal roles for retinoid signaling and the DERARE in maintaining HSCs and preventing leukemogenesis by coordinate regulation of Hoxb genes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to describe the secular trends in drug-resistant tuberculosis (DR-TB) and to identify unique characteristics of multidrug-resistant tuberculosis (MDR-TB) in rural China., Methods: A retrospective study was conducted using TB data collected from 36 TB prevention and control institutions serving rural populations in Shandong Province, China, for the period 2006-2015., Results: Approximately 8.3% of patients suffered from MDR-TB, among whom 70% were newly treated patients; this rate increased by 1.3% annually during the 10-year study period. An increase in the percentage of overall first-line drug resistance against isoniazid, rifampicin, ethambutol, and streptomycin was confirmed (p<0.05). The percentage of MDR-TB in new and previously treated cases increased at yearly rates of 9.9% and 11.1%, respectively. MDR-TB patients were more likely to be female (odds ratio (OR) 1.58, 95% confidence interval (CI) 1.32-1.89), smokers (OR 1.75, 95% CI 1.47-2.07), to have had recent TB contact (OR 1.58, 95% CI 1.04-2.42), or to have been retreated (OR 2.89, 95% CI 2.46-3.41)., Conclusions: Increasing MDR-TB and rates of primary MDR-TB characterize DR-TB cases in rural China. Persistent efforts need to be made among MDR-TB patients in future TB control strategies., (Copyright © 2017. Published by Elsevier Ltd.)

Microbial drug resistance has become a major public health concern worldwide. To acquire epidemiologic data on drug-resistant tuberculosis (DR TB) among children, a major cause of illness and death for this population, we conducted a retrospective study of 2006-2015 data from 36 TB prevention and control institutions in Shandong Province, China. A total of 14,223 new TB cases, among which children (<18 years of age) accounted for only 5.5%, were caused by culture-confirmed Mycobacterium tuberculosis. Among children with TB, 18.9% had DR TB and 6.9% had multidrug-resistant TB. Over the past decade, the percentage of DR TB; multidrug-resistant TB; and overall first-line drug resistance for isoniazid, rifampin, ethambutol, and streptomycin among children increased significantly (at least 12%). Understanding the long-term trends of DR TB among children can shed light on the performance of TB control programs, thereby contributing to global TB control.

Transgenic rice producing insecticidal proteins from Bacillus thuringiensis (Bt) could help protect the plants from damage by lepidopteran pests. However, one concern is the potential of Bt rice to harm non-target natural enemies, which play a vital role in pest control. In the present study, the potential effects of Cry1C rice and Cry2A rice on different life-table parameters and population dynamics of Pseudogonatopus flavifemur, a parasitoid of rice planthoppers, were evaluated under laboratory and field condition. The exposure of P. flavifemur to plant-produced Bt proteins was also analyzed. Results indicated that direct feeding on rice plants was the main exposure pathway of P. flavifemur to the Cry1C and Cry2A proteins. No significant difference on the development, survival, longevity, fecundity, and prey consumption of P. flavifemur was detected over two generations between the Bt and non-Bt rice treatments. Furthermore, the population dynamics of P. flavifemur were not affected by Cry1C rice and Cry2A rice. In conclusion, the tested Cry1C rice and Cry2A rice do not appear to harm the parasitoid P. flavifemur.

Background: Extensively Drug-Resistant (XDR) Tuberculosis (TB) has posed a great threat to global health and finance systems, especially for developing countries with high TB and Multidrug-Resistant (MDR) TB burden., Methods: We retrospectively analyzed HIV-uninfected TB case confirmed and treated in Shandong Provincial Chest Hospital (SPCH) between January 2008 and December 2015. Unique characteristics of XDR-TB were identified; its longitudinal changes and survival were analyzed., Results: Between January 2008 and December 2015, a total of 144 cases were confirmed to be XDR-TB (2.5% of 5663 culture-confirmed TB cases; 27.9% of 516 MDR-TB cases). The proportion of XDR TB cases among MDR-TB cases has increased from 26.5% in 2008 to 44.5% in 2014 (Chi-Square test for trends: P < 0.01). Among the 144 XDR-TB cases, 21 patients (14.6%) had treatment success, 123 (85.1%) had poor treatment outcomes. Mortality was higher among XDR-TB cases than among MDR TB cases (8.3% vs. 3.8%, P = 0.033) and drug-susceptible TB cases (8.3% vs. 2.1%, P < 0.01)., Conclusions: XDR-TB cases comprise a substantial and increasing fraction of MDR-TB cases, causing poor treatment outcomes and high mortalities. Early drug susceptibility testing, adequate TB treatment and efficient infection control must be in place in future TB control strategies.