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Sulfamethoxazole (SMX) is a widespread and persistent pollutant in the environment. Although the screening and analysis of SMX-degrading bacteria have been documented, the interaction mechanisms of functional microorganisms are still poorly understood. This study constructed a consortium with strain YL1 and YL2 supplied with SMX as the sole carbon and energy source. The coexisting mechanism and the removal of SMX of the consortium were investigated. The total oxidizable carbon (TOC) removal rate of the combined bacterial system was 38.94% compared to 29.45% for the single bacterial system at the same biomass. The mixed bacterial consortium was able to resist SMX at concentrations up to 400 mg/L and maintained a stable microbial structure at different culture conditions. The optimum conditions found for SMX degradation were 30 °C, pH 7.0, a shaking speed of 160 r·min−1, and an initial SMX concentration of 200 mg·L−1. The degradation of SMX was accelerated by the addition of YL2 for its ability to metabolize the key intermediate, 4-aminophenol. The removal rate of 4-aminophenol by strain YL2 reached 19.54% after 5 days. Genome analysis revealed that adding riboflavin and enhancing the reducing capacity might contribute to the degradation of SMX. These results indicated that it is important for the bioremediation of antibiotic-contaminated aquatic systems to understand the metabolism of bacterial communities.

Summary: The diaphragm is critical for respiration and separation of the thoracic and abdominal cavities, and defects in diaphragm development are the cause of congenital diaphragmatic hernias (CDH), a common and often lethal birth defect. The genetic etiology of CDH is complex. Single-nucleotide variants (SNVs), insertions/deletions (indels), and structural variants (SVs) in more than 150 genes have been associated with CDH, although few genes are recurrently mutated in multiple individuals and mutated genes are incompletely penetrant. This suggests that multiple genetic variants in combination, other not-yet-investigated classes of variants, and/or nongenetic factors contribute to CDH etiology. However, no studies have comprehensively investigated in affected individuals the contribution of all possible classes of variants throughout the genome to CDH etiology. In our study, we used a unique cohort of four individuals with isolated CDH with samples from blood, skin, and diaphragm connective tissue and parental blood and deep whole-genome sequencing to assess germline and somatic de novo and inherited SNVs, indels, and SVs. In each individual we found a different mutational landscape that included germline de novo and inherited SNVs and indels in multiple genes. We also found in two individuals a 343 bp deletion interrupting an annotated enhancer of the CDH-associated gene GATA4, and we hypothesize that this common SV (found in 1%–2% of the population) acts as a sensitizing allele for CDH. Overall, our comprehensive reconstruction of the genetic architecture of four CDH individuals demonstrates that the etiology of CDH is heterogeneous and multifactorial.

Assessing the impacts of climate change on geographic distribution by identifying how biological response relates to environmental conditions is important for addressing the adverse effects of climate change. Using the maximum entropy algorithm and spatial analysis module of ArcGIS, we construct a habitat prediction model for the geographic distribution of alpine vegetation in the Hengduan Mountains of southwestern China. We use the model to identify how alpine vegetation has responded to climatic changes during the period 1980–2018, and to predict responses to possible temperature and precipitation changes in the future. The results indicate that the geographic distribution of alpine vegetation in the Hengduan Mountains is most sensitive to annual mean minimum temperature variation. The most suitable habitat for alpine vegetation under climate change is in northernmost Sichuan, in the Hengduan–Himalayan mountain area, at elevations from 4500 to 5000 masl. The current area of alpine vegetation in the Hengduan Mountains accounts for 8.20% of their total area. As the annual mean temperature increases, the area suitable for alpine vegetation increases by 0.32–1.27%, regardless of changes in precipitation. When the temperature increases by 1–2°C, the area unsuitable for alpine vegetation decreases by 1.64–2.97%. These results indicate that a temperature increase influences the geographic distribution pattern of alpine vegetation in the Hengduan Mountains. The most notable effect was under the 2°C increase scenario. The predictions suggest that under future climate change, the geographic distribution of alpine vegetation will continue to shift toward middle and higher elevations. To protect endemic alpine vegetation, the best habitats should be protected from interference and destruction by human activities.

The aim of this study was to prepare a promising biomaterial for bone tissue repair and regeneration. The Strontium – calcium sulfate hemihydrate (Sr-α-CaS) scaffold incorporating gelatin microspheres (GMs) encapsulated with Ginsenoside Rg1 (Rg1) was designed. The scaffolds of Rg1/GMs/Sr-α-CaS showed sustained release of Rg1, good biocompatibility and ability of promoting osteogenic differentiation and angiogenesis in vitro. The scaffolds were implanted into animal model of cranial bone defect to characterize bone tissue repair and regeneration in vivo. From the images of Micro-CT, it was obvious that the most bone tissue was formed in Rg1/GMs/Sr-α-CaS group in 12 weeks. New bone structure, collagen and mineralization were analyzed with staining of HE, Masson and Safranin O-Fast green and showed good distribution. The expression of osteocalcin of Rg1/GMs/Sr-α-CaS indicated new bone formation in defect site. The results revealed that synergy of Rg1 and Sr showed the best effect of bone repair and regeneration, which provided a new candidate for bone defect repair in clinic.

Sequencing-based identification of tumor tissue-of-origin (TOO) is critical for patients with cancer of unknown primary lesions. Even if the TOO of a tumor can be diagnosed by clinicopathological observation, reevaluations by computational methods can help avoid misdiagnosis. In this study, we developed a neural network (NN) framework using the expression of a 150-gene panel to infer the tumor TOO for 15 common solid tumor cancer types, including lung, breast, liver, colorectal, gastroesophageal, ovarian, cervical, endometrial, pancreatic, bladder, head and neck, thyroid, prostate, kidney, and brain cancers. To begin with, we downloaded the RNA-Seq data of 7,460 primary tumor samples across the above mentioned 15 cancer types, with each type of cancer having between 142 and 1,052 samples, from the cancer genome atlas. Then, we performed feature selection by the Pearson correlation method and performed a 150-gene panel analysis; the genes were significantly enriched in the GO:2001242 Regulation of intrinsic apoptotic signaling pathway and the GO:0009755 Hormone-mediated signaling pathway and other similar functions. Next, we developed a novel NN model using the 150 genes to predict tumor TOO for the 15 cancer types. The average prediction sensitivity and precision of the framework are 93.36 and 94.07%, respectively, for the 7,460 tumor samples based on the 10-fold cross-validation; however, the prediction sensitivity and precision for a few specific cancers, like prostate cancer, reached 100%. We also tested the trained model on a 20-sample independent dataset with metastatic tumor, and achieved an 80% accuracy. In summary, we present here a highly accurate method to infer tumor TOO, which has potential clinical implementation.

Identification of the target genes of microRNAs (miRNAs), trans-acting small interfering RNAs (ta-siRNAs), and small interfering RNAs (siRNAs) is an important step for understanding their regulatory roles in plants. In recent years, many bioinformatics software packages based on small RNA (sRNA) high-throughput sequencing (HTS) and degradome sequencing data analysis have provided strong technical support for large-scale mining of sRNA-target pairs. However, sRNA-target regulation is achieved using a complex network of interactions since one transcript might be co-regulated by multiple sRNAs and one sRNA may also affect multiple targets. Currently used mining software can realize the mining of multiple unknown targets using known sRNA, but it cannot rule out the possibility of co-regulation of the same target by other unknown sRNAs. Hence, the obtained regulatory network may be incomplete. We have developed a new mining software, sRNATargetDigger, that includes two function modules, "Forward Digger" and "Reverse Digger", which can identify regulatory sRNA-target pairs bidirectionally. Moreover, it has the ability to identify unknown sRNAs co-regulating the same target, in order to obtain a more authentic and reliable sRNA-target regulatory network. Upon re-examination of the published sRNA-target pairs in Arabidopsis thaliana, sRNATargetDigger found 170 novel co-regulatory sRNA-target pairs. This software can be downloaded from http://www.bioinfolab.cn/sRNATD.html.

Objective: Changes in the number of various tumor-infiltrating lymphocytes (TILs) and degrees of vascular normalization in breast cancer (BC) patients after neoadjuvant chemotherapy (NAC) were analyzed to screen key factors that can predict the prognosis.Methods: HE-stained sections were used to assess the degree of TILs infiltration; immunohistochemically stained sections were used to assess the infiltration of CD8+, CD4+, FOXP3+ Tregs and the expression of PD-L1; immunofluorescence-stained sections were used to assess the microvessel density (MVD) and microvessel pericyte coverage index (MPI). The expression of them before NAC were compared with those after NAC, and correlations between changes in these parameters and the pathological complete remission (pCR) and DFS of BC patients were analyzed.Results: After NAC, the percentage of patients with enhanced sTILs in the pCR group was significantly higher than that in the Non-pCR group (P < 0.05). Univariate and multivariate analyses showed that the number of FOXP3+ Tregs and MPI before NAC were correlated with pCR (P < 0.05). Survival analysis showed that the DFS of BC patients with reduced FOXP3+ Tregs was significantly better than that of patients with elevated FOXP3+ Tregs (P = 0.029). The sTILs count and MPI were significantly higher in primary tumors than lymph nodes (P < 0.05).Conclusion: After NAC, the reduced infiltration of FOXP3+ Tregs was correlated with an improvement in DFS in BC patients. Changes in the number of FOXP3+ Tregs and the MPI may be used as prognostic markers for BC patients.

The performance of Rumex nepalensis, an important medicinal herb, varies significantly among subalpine grasslands, shrublands and forest ecosystems in southwestern China. Plant–soil feedback is receiving increasing interest as an important driver influencing plant growth and population dynamics. However, the feedback effects of soils from different ecosystems on R. nepalensis remain poorly understood. A greenhouse experiment was carried out to identify the effects of different soil sources on the photosynthesis and biomass of R. nepalensis. R. nepalensis was grown in soils collected from the rooting zones of R. nepalensis (a grassland soil, RS treatment), Hippophae rhamnoides (a shrub soil, HS treatment), and Picea asperata (a forest soil, PS treatment). The chlorophyll contents, net photosynthetic rates, and biomasses of R. nepalensis differed significantly among the three soils and followed the order of RS > HS > PS. After soil sterilization, these plant parameters followed the order of RS > PS > HS. The total biomass was 16.5 times higher in sterilized PS than in unsterilized PS, indicating that the existence of soil microbes in P. asperata forest ecosystems could strongly inhibit R. nepalensis growth. The root to shoot biomass ratio of R. nepalensis was the highest in the sterilized PS but the lowest in the unsterilized PS, which showed that soil microbes in PS could change the biomass allocation. Constrained redundancy analysis and path analysis suggested that soil microbes could impact the growth of R. nepalensis via the activities of soil extracellular enzymes (e.g., β-1,4-N-acetylglucosaminidase (NAG)) in live soils. The soil total soluble nitrogen concentration might be the main soil factor regulating R. nepalensis performance in sterilized soils. Our findings underline the importance of the soil microbes and nitrogen to R. nepalensis performance in natural ecosystems and will help to better predict plant population dynamics.

Pelvic lymphadenectomy procedure is included as part of the standard protocol of radical hysterectomy for women with early-stage cervical cancer (Stage IA to IB1). However, an important sequel to lymphadenectomy procedure is the possible occurrence of lymphedema in the lower abdomen and lower extremities. Previous researches also find that women with lymphedema experience many emotional impacts, including depression, anxiety, and adjustment problems. Only approximately 10% of women with clinical stage IB cervical carcinoma were involved with metastatic disease. If we could better define the relevant lymphatic nodes that must be removed, it is then possible to limit routinely performed lymphadenectomy for regional nodal metastasis in the pelvis, and hence reduce the need for extended surgical staging (para-aortic lymphadenectomy). We systematically reviewed a body of literature and updated available information concerning the current progress on the application of sentinel lymph node biopsy in women with early-stage cervical cancer. All detection methods (preoperative injection of radiocolloid tracer, intraoperative injection of blue dye, or a combination of both techniques) demonstrated reasonable sensitivity (with a few exceptions), high specificity, low false-negative rate and high negative predictive value. The review of the literature in this paper should convince the readers that sentinel lymph node biopsy has the potential to improve the quality of life and the possibility to maintain relapse-free survival for women with cervical cancer. The proper identification of negative sentinel lymph node allows individualized therapy and may preclude the need of lymphadenectomy procedure in most of these women. Keywords: Cervix, Lymphadenectomy, Lymphoscintigraphy, Sentinel lymph node, Staging

Background/Aims: To evaluate the clinicopathologic aspects of small cell neuroendocrine carcinoma of the uterine cervix (SCNEC). Methods: A retrospective review of 40 patients with SCNEC in 3 hospitals from 2009 to 2015 was conducted to assess the survival rates and examine the associations between clinicopathological variables and overall survival (OS). A meta-analysis of 22 studies containing 1901 patients was also conducted to further confirm the results. Results: In the clinical group of 40 patients, the 5-year OS rate was 20%. Advanced International Federation of Gynecology and Obstetrics (FIGO) stage and radiation therapy (RT) were associated with poor survival. However, radical surgery was associated with prolonged survival. In the meta-analysis of 1901 patients, the 2-year disease-free survival (DFS) rate, 5-year DFS rate, 2-year OS rate, 3-year OS rate and 5-year OS rate of SCNEC were 48%, 35%, 62%, 35%, and 35% respectively. Advanced FIGO stage, larger tumor size, lymph node metastasis (LNM) (+), lymphovascular space involvement (LVSI) (+), parametrial involvement (PI) (+), depth of stromal invasion (DSI) > 2/3, and RT were associated with poor survival. However, a chemotherapy regimen similar to that for small cell lung cancer was associated with prolonged survival. Conclusion: Advanced FIGO stage, larger tumor size, LNM (+), LVSI (+), DSI > 2/3, PI (+), and RT were independent predictors of poor prognosis of SCNEC. Radical surgery combined with a chemotherapy regimen similar to that of small cell lung cancer may be a potential therapeutic approach for SCNEC.

The purpose of this study was to investigate the synergistic and bactericidal effects of combinations of colistin with meropenem or amikacin in vitro and provide laboratory data needed for development of therapeutic strategies for the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection. We found that minimum inhibitory concentration (MIC) of colistin, meropenem and amikacin were 2~32, 4~256, and 1~16384 μg/ml, respectively. The minimum bactericidal concentration of the antibiotics was either 1× or 2×MIC. Treatments of 6 CRKP isolates at 1 μg/ml colistin completely killed 2 of them and suppressed 4 others growth. 4 CRKP isolates at 16 μg/ml meropenem or amikacin completely killed and suppressed 2 others growth. 2 CRKP isolates showed synergic effects in all colistin combination and 3 CRKP isolates showed synergic effects in part of colistin combination. Our data suggest that colistin in combination with either meropenem or amikacin could be a valid therapeutic option against colistin-resistant CRKP isolates. Moreover, the combination of colistin-amikacin is less expensive to treat CRKP infections in Eastern Heilongjiang Province.

Micro-nano scale pores can accurately and fastly be measured by the nuclear magnetic resonance (NMR) technique, which provides a new method to quantitatively characterize pore structures in tight sandstone. Based on the method of calibration of mercury pressure data for NMR T2 spectrum, for the measurement inaccuracy due to the mercury saturation less than 100% in tight sandstone, the mercury pressure curve and T2 spectrum is used to cumulate from the maximum pore on the right boundary to the small pores in the left, the range of pore-throat radius measured by the mercury injection in the leftward cumulative curve is selected as a comparable interval of NMR pore-throat radius, and the longitudinal interpolation method and the least square method are utilized to construct the distribution curve of pore-throat radius transformed by T2 spectrum. The modified method is used to obtain NMR T2 spectrum, conversion coefficient of pore-throat radius and pore-throat radius distribution of the Carboniferous-Permian tight sandstone gas reservoirs in the eastern Linqing depression, and characteristics of reservoir pore structures are quantitatively investigated; in addition, in combination with analysis of thin section and scanning electron microscopy, the reservoir effectiveness and cause of the pore structure variability in the tight sandstone are also well studied. The results show that the NMR pore-throat radius curve obtained by the modified method has a high consistency with the mercury injection curve, and the NMR test accuracy of tight sandstone is significantly improved. In the study area, the pore-throat radius of the Carboniferous-Permian tight sandstone mainly ranges from 0.002 to 2 μm, the pore is generally submicro-nano scale, but the pore-throat radius distribution of different types of sandstone varies significantly. The lithic quartz sandstone is rich in siliceous matter and poor in plastic detritus and matrix, generally dominated by submicro-scale pore-throats including micro-scale pore-throats; lithic feldspar sandstone and quartz-rich feldspar lithic sandstone are rich in quartz and poor in plastic detritus and matrix, dominated by submicro-nano scale pore-throats (nano-scale pore-throats predominantly); the lithic fragment-rich feldspar lithic sandstone and lithic sandstone are poor in quartz and rich in plastic detritus and matrix, mainly dominated by nano-scale pore-throats smaller than 0.05 μm. Micropetrographic components are key factors to control pore structure difference and reservoir effectiveness, and the reservoir quality may be macroscopically controlled by sedimentary microfacies; the lithic quartz sandstones of coarse- and fine-grained point bar/riverbed microfacies are the most favorable reservoirs; the lithic feldspar sandstone of fine-grained point bar microfacies, the quartz-rich feldspar lithic sandstone of fine-grained distributary channel and barrier bar microfacies are relatively favorable reservoirs, while both lithic fragment-rich feldspar lithic sandstone and lithic sandstone of tidal-flat facies are ineffective reservoirs with very poor porosity and permeability. Keywords: NMR T2 spectrum, Mercury injection, Conversion coefficient, Pore-throat, Rock fabric, Microfacies, Tight sandstone, Linqing depression

Background: Bilateral sudden sensorineural hearing loss (BSSHL) is rare and assumed to be a different clinical entity compared to unilateral SSHL (USSHL). This study examined the differences between the idiopathic BSSHL and USSHL. Methods: Forty-six sequential BSSHL patients (Se-BSSHL) and 68 simultaneous BSSHL (Si-BSSHL) were consecutively admitted between June 2008 and December 2015. Two sets of patients served as control groups: (1) USSHL patients with healthy contralateral ear and (2) USSHL patients with contralateral preexisting hearing loss (USSHLwCHL). We retrospectively analyzed differences among four cohorts using analysis of variance, Kruskal-Wallis test, Welch's t-test, and Chi-square test as appropriate before and after propensity score matching (PSM) based on age, gender, and body mass index (BMI). Results: The prevalence of idiopathic BSSHL was 8.6% (114/1329) among the total SSHL patients. In the total cohort, USSHL patients tended to be younger, female, and tended to have lower BMI, renal parameters, and total cholesterol in addition to higher high-density lipoprotein compared to the other three groups. Most routine blood indicators, some coagulation markers, and immunoglobulin M (H = 13.4, P = 0.004) were significantly different among the study groups. After PSM, the major significant differences were found in audiometric characteristics. Si-BSSHL and Se-BSSHL patients demonstrated similar hearing thresholds as USSHL but were significantly better than the USSHLwCHL patients across most frequencies before and after treatment (H = 30.0, P < 0.001 for initial hearing and H = 12.0, P = 0.007 for final hearing). Moreover, the BSSHL patients showed different hearing loss distribution patterns (more descending type, χ2 = 33.8, P = 0.001) with less hearing gain (H = 17.5, P < 0.001) compared to the USSHL patients. Conclusions: Idiopathic BSSHL is a relatively rare subtype of SSHL with a higher rate of descending audiogram type and inferior hearing outcome rather than being classified as a completely different disease entity compared to USSHL.

The COVID-19 vaccination behavior of people living with HIV (PLWH) was examined via a cross-sectional web-based survey of PLWH aged 18 years and older. The survey was conducted from l May to 20 June 2021. The survey included social demographic information; vaccination behavior (B); and questions related to perceived usefulness (PU), perceived risk (PR), subjective norms (SNs), perceived behavior control (PBC), and behavior intention (BI). The associations between the questionnaire variables and COVID-19 vaccination behavior were assessed by calculating the descriptive data, correlation analysis, and structural equation modeling. In total, 43.71% of the 350 eligible respondents had received a COVID-19 vaccine. The differences in COVID-19 vaccination behavior according to age, gender, religious belief, marital status, income, education level, and occupation were not obvious (p > 0.05). PU had a significantly negative effect on PR (p < 0.05). PR had a significantly negative effect on BI (p < 0.05). SNs had a significantly positive effect on BI (p < 0.05). BI had a significantly positive effect on B (p < 0.05). PR fully mediated the effects of PU on BI, BI fully mediated the effects of PR on B, and BI fully mediated the effects of SNs on B (p < 0.05). Health policymakers and medical workers should provide more information about the risks of vaccine application to improve the vaccination behavior of PLWH.

Biodegradation of 1,4-dioxane (dioxane) contamination has gained much attention for decades. In our previous work, we isolated a highly efficient dioxane degrader, Xanthobacter sp. YN2, but the underlying mechanisms of its extraordinary degradation performance remained unresolved. In this study, we performed a comparative transcriptome analysis of YN2 grown on dioxane and citrate to elucidate its genetic degradation mechanism and investigated the transcriptomes of different dioxane degradation stages (T0, T24, T48). We also analyzed the transcriptional response of YN2 over time during which the carbon source switched from citrate to dioxane. The results indicate that strain YN2 was a methylotroph, which provides YN2 a major advantage as a pollutant degrader. A large number of genes involved in dioxane metabolism were constitutively expressed prior to dioxane exposure. Multiple genes related to the catabolism of each intermediate were upregulated by treatment in response to dioxane. Glyoxylate metabolism was essential during dioxane degradation by YN2, and the key intermediate glyoxylate was metabolized through three routes: glyoxylate carboligase pathway, malate synthase pathway, and anaplerotic ethylmalonyl–CoA pathway. Genes related to quorum sensing and transporters were significantly upregulated during the early stages of degradation (T0, T24) prior to dioxane depletion, while the expression of genes encoding two-component systems was significantly increased at late degradation stages (T48) when total organic carbon in the culture was exhausted. This study is the first to report the participation of genes encoding glyoxalase, as well as methylotrophic genes xoxF and mox, in dioxane metabolism. The present study reveals multiple genetic and transcriptional strategies used by YN2 to rapidly increase biomass during growth on dioxane, achieve high degradation efficiency and tolerance, and adapt to dioxane exposure quickly, which provides useful information regarding the molecular basis for efficient dioxane biodegradation.

Function expansion of fiber sensor is highly desired for ultrasensitive optical detection and analysis. Here, we present an approach of multifunctional fiber sensor based on Fano resonances and localized surface plasmon resonance (LSPR) excited via cylindrical vector beam with ability of refractive index (RI) sensing, nano-distance detection, and surface enhanced Raman spectroscopy (SERS). Silver (Ag)-nanocube modified microfiber is theoretically proved to enable to detect RI of the nearby solids and gases based on Fano resonances with a sensitivity of 128.63 nm/refractive index unit (RIU) and 148.21 nm/RIU for solids and gases, respectively. The scattering spectrum of the Ag nanocube has the red-shift response to the varies of the nano-distance between the nanocube and the nearby solid, providing a detection sensitivity up to 1.48 nm (wavelength)/nm (distance). Moreover, this configuration is theoretically verified to have ability to significantly enhance electric field intensity. Radially polarized beam is proved to enhance the electric field intensity as large as 5 times in the side-face configuration compared with linear polarization beam. This fiber-based sensing method is helpful in fields of remote detection, multiple species detection, and cylindrical vector beam-based detection.

The removal of organic pollutants using green environmental photocatalytic degradation techniques urgently need high-performance catalysts. In this work, a facile one-step hydrothermal technique has been successfully applied to synthesize a Nb2O5 photocatalyst with uniform micro-flower structure for the degradation of methyl orange (MO) under UV irradiation. These nanocatalysts are characterized by transmission and scanning electron microscopies (TEM and SEM), X-ray diffraction (XRD), Brunauer–Emmett–Teller (BET) method, and UV-Vis diffuse reflectance spectroscopy (DRS). It is found that the prepared Nb2O5 micro-flowers presents a good crystal phases and consist of 3D hierarchical nanosheets with 400–500 nm in diameter. The surface area is as large as 48.6 m2 g−1. Importantly, the Nb2O5 micro-flowers exhibit superior catalytic activity up to 99.9% for the photodegradation of MO within 20 mins, which is about 60-fold and 4-fold larger than that of without catalysts (W/O) and commercial TiO2 (P25) sample, respectively. This excellent performance may be attributed to 3D porous structure with abundant catalytic active sites.

Objectives: Heteroresistance is a phenomenon in which there are various responses to antibiotics from bacterial cells within the same population. Here, we isolated and characterised an imipenem heteroresistant Acinetobacter baumannii strain (HRAB-85). Methods: The genome of strain HRAB-85 was completely sequenced and analysed to understand its antibiotic resistance mechanisms. Population analysis and multilocus sequence typing were performed. Results: Subpopulations grew in the presence of imipenem at concentrations of up to 64 μg/mL, and the strain was found to belong to ST208. The total length of strain HRAB-85 was 4,098,585 bp with a GC content of 39.98%. The genome harboured at least four insertion sequences: the common ISAba1, ISAba22, ISAba24, and newly reported ISAba26. Additionally, 19 antibiotic-resistance genes against eight classes of antimicrobial agents were found, and 11 genomic islands (GIs) were identified. Among them, GI3, GI10, and GI11 contained many ISs and antibiotic-resistance determinants. Conclusions: The existence of imipenem heteroresistant phenotypes in A. baumannii was substantiated in this hospital, and imipenem pressure, which could induce imipenem-heteroresistant subpopulations, may select for highly resistant strains. The complete genome sequencing and bioinformatics analysis of HRAB-85 could improve our understanding of the epidemiology and resistance mechanisms of carbapenem-heteroresistant A. baumannii.

Abstract Background Metastasis and recurrence are the most common reasons for treatment failure of colorectal carcinoma (CRC). Vasculogenic mimicry (VM, blood supply formation often seen in highly aggressive tumors), Aldehyde dehydrogenase 1 (ALDH1, a biomarker of cancer stem cells), KAI1 (a suppressor gene of tumor metastasis) are all valuable factors for metastasis and prognosis in diverse human cancers. However, the correlation of VM, ALDH1, KAI1 and microvessel density (MVD) in CRC is unclear. In this study, we analyzed the correlations among VM, ALDH1, KAI1 and MVD, as well as their respective correlations with clinicopathological parameters and survival in CRC. Methods The level of VM, ALDH1, KAI1 and MVD in 204 whole tissue samples of CRC were examined by immunhistochemistry. Clinical data was also collected. Results Levels of VM, ALDH1 and MVD were significantly higher, and levels of KAI1 significantly lower, in CRC tissues than in normal colorectal tissues. Levels of VM, ALDH1 and MVD were positively associated with invasion of depth, lymph node metastasis (LNM), distant metastasis and tumor-node-metastasis (TNM) stages, and negatively with patients’ overall survival (OS). Levels of KAI1 was negatively correlated with invasion of depth, LNM, distant metastasis and TNM stages, and the KAI1 positive expression subgroup had significantly longer OS than did the KAI1- subgroup. In multivariate analysis, high levels of VM, ALDH1 and KAI1, as well as TNM stages were independently correlated with lower OS in patients with CRC. Conclusions VM, MVD and the expression of ALDH1 and KAI1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets for CRC.

Background: The molecular genetic research showed the association between X-linked hearing loss and mutations in POU3F4. This research aimed to identify a POU3F4 mutation in a nonsyndromic X-linked recessive hearing loss family. Methods: A series of clinical evaluations including medical history, otologic examinations, family history, audiologic testing, and a high-resolution computed tomography scan were performed for each patient. Bidirectional sequencing was carried out for all polymerase chain reaction products of the samples. Moreover, 834 controls with normal hearing were also tested. Results: The pedigree showed X-linkage recessive inheritance pattern, and pathogenic mutation (c.499C>T) was identified in the proband and his family member, which led to a premature termination prior to the entire POU domains. This mutation co-segregated with hearing loss in this family. No mutation of POU3F4 gene was found in 834 controls. Conclusions: A nonsense mutation is identified in a family displaying the pedigree consistent with X-linked recessive pattern in POU3F4 gene. In addition, we may provide molecular diagnosis and genetic counseling for this family.

Background: Hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome is an autosomal dominant disorder primarily caused by haploinsufficiency of GATA binding protein 3 (GATA3) gene mutations, and hearing loss is the most frequent phenotypic feature. This study aimed at identifying the causative gene mutation for a three-generation Chinese family with HDR syndrome and analyzing auditory phenotypes in all familial HDR syndrome cases. Methods: Three affected family members underwent otologic examinations, biochemistry tests, and other clinical evaluations. Targeted genes capture combining next-generation sequencing was performed within the family. Sanger sequencing was used to confirm the causative mutation. The auditory phenotypes of all reported familial HDR syndrome cases analyzed were provided. Results: In Chinese family 7121, a heterozygous nonsense mutation c.826C>T (p.R276*) was identified in GATA3. All the three affected members suffered from sensorineural deafness and hypocalcemia; however, renal dysplasia only appeared in the youngest patient. Furthermore, an overview of thirty HDR syndrome families with corresponding GATA3 mutations revealed that hearing impairment occurred earlier in the younger generation in at least nine familial cases (30%) and two thirds of them were found to carry premature stop mutations. Conclusions: This study highlights the phenotypic heterogeneity of HDR and points to a possible genetic anticipation in patients with HDR, which needs to be further investigated.

Congenital diaphragmatic hernia (CDH) is a severe birth defect that is often accompanied by other congenital anomalies. Previous exome sequencing studies for CDH have supported a role of de novo damaging variants but did not identify any recurrently mutated genes. To investigate further the genetics of CDH, we analyzed de novo coding variants in 362 proband-parent trios including 271 new trios reported in this study. We identified four unrelated individuals with damaging de novo variants in MYRF (P = 5.3x10(-8)), including one likely gene-disrupting (LGD) and three deleterious missense (D-mis) variants. Eight additional individuals with de novo LGD or missense variants were identified from our other genetic studies or from the literature. Common phenotypes of MYRF de novo variant carriers include CDH, congenital heart disease and genitourinary abnormalities, suggesting that it represents a novel syndrome. MYRF is a membrane associated transcriptional factor highly expressed in developing diaphragm and is depleted of LGD variants in the general population. All de novo missense variants aggregated in two functional protein domains. Analyzing the transcriptome of patient-derived diaphragm fibroblast cells suggest that disease associated variants abolish the transcription factor activity. Furthermore, we showed that the remaining genes with damaging variants in CDH significantly overlap with genes implicated in other developmental disorders. Gene expression patterns and patient phenotypes support pleiotropic effects of damaging variants in these genes on CDH and other developmental disorders. Finally, functional enrichment analysis implicates the disruption of regulation of gene expression, kinase activities, intra-cellular signaling, and cytoskeleton organization as pathogenic mechanisms in CDH.

In order to synthesize a novel two-dimensional energetic material, nitrated graphene oxide (NGO) was prepared by the nitrification of graphite oxide to make a functional modification. Based on the morphological characterization, the NGO has a greater degree of curl and more wrinkles on the surface. The structure characterization and density functional theory calculation prove that epoxy and hydroxyl groups on the edge of graphite oxide have reacted with nitronium cation (NO2+) to produce nitro and nitrate groups. Hydrophobicity of NGO implied higher stability in storage than graphene oxide. Synchronous simultaneous analysis was used to explore the decomposition mechanism of NGO preliminarily. The decomposition enthalpy of NGO is 662.0 J·g−1 and the activation energy is 166.5 kJ·mol−1. The thermal stability is similar to that of general nitrate energetic materials. The hygroscopicity, thermal stability and flammability of NGO prove that it is a novel two-dimensional material with potential applications as energetic additives in the catalyst, electrode materials and energetic devices.

Background: The prevalence of sudden sensorineural hearing loss in children (CSSNHL) is consistently increasing. However, the pathology and prognosis of CSSNHL are still poorly understood. This retrospective study evaluated clinical characteristics and possible associated factors of CSSNHL. Methods: One hundred and thirty-six CSSNHL patients treated in Department of Otolaryngology-Head and Neck Surgery and Institute of Otolaryngology at Chinese PLA General Hospital between July 2008 and August 2015 were included in this study. These patients were analyzed for clinical characteristics, audiological characteristics, laboratory examinations, and prognostic factors. Results: Among the 136 patients (151 ears), 121 patients (121 ears, 80.1%) were diagnosed with unilaterally CSSNHL, and 15 patients (30 ears, 19.9%) with bilateral CSSNHL. The complete recovery rate of CSSNHL was 9.3%, and the overall recovery rate was 37.7%. We found that initial degree of hearing loss, onset of treatment, tinnitus, the ascending type audiogram, gender, side of hearing loss, the recorded auditory brainstem response (ABR), and distortion product otoacoustic emissions (DPOAEs) had prognostic significance. Age, ear fullness, and vertigo had no significant correlation with recovery. Furthermore, the relevant blood tests showed 30.8% of the children had abnormal white blood cell (WBC) counts, 22.1% had elevated homocysteine levels, 65.8% had high alkaline phosphatase (ALP), 33.8% had high IgE antibody levels, and 86.1% had positive cytomegalovirus (CMV) IgG antibodies. Conclusions: CSSNHL commonly occurs unilaterally and results in severe hearing loss. Initial severe hearing loss and bilateral hearing loss are negative prognostic factors for hearing recovery, while positive prognostic factors include tinnitus, gender, the ascending type audiogram, early treatment, identifiable ABR waves, and DPOAEs. Age, vertigo, and ear fullness are not correlated with the recovery. Some serologic indicators, including the level of WBC, platelet, homocysteine, ALP, positive CMV IgG antibody, fibrinogen, and some immunologic indicators, are closely related to CSSNHL.

AIM: To investigate the value of 3D- optical coherence tomography(OCT)in the diagnosis of macular disease before phacoemulsification. METHODS: Clinical records of 423 cataract patients(512 eyes)who underwent phacoemulsification combined with intraocular lens implantation in our hospital from June to December in 2015 were retrospectively analyzed. In addition to preoperative routine examination of fundus, Topcon 3D-OCT 2000 was used to examine the macula, the detection rate of macular disease was compared, risk factors of cataract combined with macular disease were analyzed. RESULTS: The OCT image results of 305 cases(384 eyes, 72.1%)were successfully obtained, 133 cases showed macular disease(146 eyes), the detection rate was 28.5%(95%CI: 27.64%-29.40%); the macular disease of 35 cases(37 eyes)were detected by routine examination of fundus before operation, the detection rate was 7.2%(95%CI: 6.72%-7.74%); the detection rate of 3D-OCT was significantly higher than routine examination of fundus for macular disease(χ2=79.05, PCI:1.091,2.664), 1.893(95%CI:1.219,2.939), 6.593(95%CI:2.027,21.447)and 95%CI: 5.130(2.841,9.263)respectively, the risk of cataract combined with macular disease showed an increasing trend with rising age. CONCLUSION: In preoperative examination of cataract patients, 3D-OCT has higher sensitivity in the detection of macular disease, especially for women, over 65 years old, high myopia and surgical history of diseased eye, 3D-OCT can be used as a routine preoperative examination.

The incorporation of metal heteroatoms into zeolites is an effective modification strategy for enhancing their catalytic performance. Herein, for the first time we report a generalized methodology for inserting metal heteroatoms (such as Sn, Fe, Zn, and Co) into the layered zeolite precursor RUB-36 via interlayer expansion by using the corresponding metal acetylacetate salt. Through this generalized methodology, Sn-JHP-1, Fe-JHP-1, Zn-JHP-1 and Co-JHP-1 zeolites could be successfully prepared by the reaction of RUB-36 and corresponding metal acetylacetate salt at 180 °C for 24 h in the presence of HCl solution. As a typical example, Sn-JHP-1 and calcined Sn-JHP-1 (Sn-JHP-2) zeolite is well characterized by the X-ray diffraction (XRD), diffuse reflectance ultraviolet-visible (UV-Vis), inductively coupled plasma (ICP), N2 sorption, temperature-programmed-desorption of ammonia (NH3-TPD) and X-ray photoelectron spectroscopy (XPS) techniques, which confirm the expansion of adjacent interlayers and thus the incorporation of isolated Sn sites within the zeolite structure. Notably, the obtained Sn-JHP-2 zeolite sample shows enhanced catalytic performance in the conversion of glucose to levulinic acid (LA) reaction.

Children’s paintings reflect their growth environments and psychological conditions, and these growth environments represent children’s family and educational environments in primary schools. The characteristics of these paintings change as children grow, and children’s expressiveness in the paintings also improves. Children’s paintings are a representation of their perceptions of things; children transform their perceptions into images that can be understood and observed by people. This research studies the growth characteristics of children based on professional painting techniques. A digital image analysis method was used to analyze the painting techniques of children aged between 7 and 13. The growth characteristics of the different age groups were combined to analyze the representative characteristics of children’s paintings at different ages. Lastly, the results of part of a questionnaire survey were used to assist in studying these characteristics. Analysis of these paintings shows that children have a poor ability to control the scale of the objects. Furthermore, the details of the objects are ignored, and children have a poor imitation ability. Young children have lower spatial cognitive abilities than older children, and girls prefer to participate in painting more than boys.

Painting materials are one of the mediums that help painters to show the effects of paintings. The use of different painting materials can help the painter to display different painting styles and artistic conception. Six hundred sixty-seven children aged 7 to 13 participated in the study. This study is mainly about the impact of the use of different painting materials on children’s painting creation. The questionnaire survey was conducted based on primary school fine arts education to study the influence of painting materials on children’s painting ability. The content of the questionnaire survey was to investigate children’s usage of different painting materials in painting works and the grasp of painting materials knowledge. This research also provided some painting materials training methods for primary school fine arts teachers to guide children to use different painting materials for painting creation based on the study results.

Dent disease 1 (DD1) is a renal salt-wasting tubulopathy associated with mutations in the Cl-/H+ antiporter ClC-5. The disease typically manifests with proteinuria, hypercalciuria, nephrocalcinosis, and nephrolithiasis but is characterized by large phenotypic variability of no clear origin. Several DD1 cases have been reported lately with additional atypical hypokalemic metabolic alkalosis and hyperaldosteronism, symptoms usually associated with another renal disease termed Bartter syndrome (BS). Expression of the Bartter-like DD1 mutant ClC-5 G261E in HEK293T cells showed that it is retained in the ER and lacks the complex glycosylation typical for ClC-5 WT. Accordingly, the mutant abolished CLC ionic transport. Such phenotype is not unusual and is often observed also in DD1 ClC-5 mutants not associated with Bartter like phenotype. We noticed, therefore, that one type of BS is associated with mutations in the protein barttin that serves as an accessory subunit regulating the function and subcellular localization of ClC-K channels. The overlapping symptomatology of DD1 and BS, together with the homology between the proteins of the CLC family, led us to investigate whether barttin might also regulate ClC-5 transport. In HEK293T cells, we found that barttin cotransfection impairs the complex glycosylation and arrests ClC-5 in the endoplasmic reticulum. As barttin and ClC-5 are both expressed in the thin and thick ascending limbs of the Henle’s loop and the collecting duct, interactions between the two proteins could potentially contribute to the phenotypic variability of DD1. Pathologic barttin mutants differentially regulated trafficking and processing of ClC-5, suggesting that the interaction between the two proteins might be relevant also for the pathophysiology of BS. Our findings show that barttin regulates the subcellular localization not only of kidney ClC-K channels but also of the ClC-5 transporter, and suggest that ClC-5 might potentially play a role not only in kidney proximal tubules but also in tubular kidney segments expressing barttin. In addition, they demonstrate that the spectrum of clinical, genetic and molecular pathophysiology investigation of DD1 should be extended.

ObjectivesThe PROMIS-Preference (PROPr) score is a recently developed summary score for the Patient-Reported Outcomes Measurement Information System (PROMIS). PROPr is a preference-based scoring system for seven PROMIS domains created using multiplicative multi-attribute utility theory. It serves as a generic, societal, preference-based summary scoring system of health-related quality of life. This manuscript evaluates construct validity of PROPr in two large samples from the US general population.MethodsWe utilized 2 online panel surveys, the PROPr Estimation Survey and the Profiles-Health Utilities Index (HUI) Survey. Both included the PROPr measure, patient demographic information, self-reported chronic conditions, and other preference-based summary scores: the EuroQol-5D (EQ-5D-5L) and HUI in the PROPr Estimation Survey and the HUI in the Profiles-HUI Survey. The HUI was scored as both the Mark 2 and the Mark 3. Known-groups validity was evaluated using age- and gender-stratified mean scores and health condition impact estimates. Condition impact estimates were created using ordinary least squares regression in which a summary score was regressed on age, gender, and a single health condition. The coefficient for the health condition is the estimated effect on the preference score of having a condition vs. not having it. Convergent validity was evaluated using Pearson correlations between PROPr and other summary scores.ResultsThe sample consisted of 983 respondents from the PROPr Estimation Survey and 3,000 from the Profiles-HUI survey. Age- and gender-stratified mean PROPr scores were lower than EQ-5D and HUI scores, with fewer subjects having scores corresponding to perfect health on the PROPr. In the PROPr Estimation survey, all 11 condition impact estimates were statistically significant using PROPr, 8 were statistically significant by the EQ-5D, 7 were statistically significant by HUI Mark 2, and 9 were statistically significant by HUI Mark 3. In the Profiles-HUI survey, all 21 condition impact estimates were statistically significant using summary scores from all three scoring systems. In these samples, the correlations between PROPr and the other summary measures ranged from 0.67 to 0.70.ConclusionsThese results provide evidence of construct validity for PROPr using samples from the US general population.

Rabies is an ancient disease but remains endemic in most parts of the world and causes approximately 59,000 deaths annually. The mechanism through which the causative agent, rabies virus (RABV), evades the host immune response and infects the host central nervous system (CNS) has not been completely elucidated thus far. Our previous studies have shown that lab-attenuated, but not wild-type (wt), RABV activates the innate immune response in the mouse and dog models. In this present study, we demonstrate that lab-attenuated RABV causes abortive infection in astrocytes, the most abundant glial cells in the CNS. Furthermore, we found that lab-attenuated RABV produces more double-stranded RNA (dsRNA) than wt RABV, which is recognized by retinoic acid-inducible gene I (RIG-I) or melanoma differentiation-associated protein 5 (MDA5). Activation of mitochondrial antiviral-signaling protein (MAVS), the common adaptor molecule for RIG-I and MDA5, results in the production of type I interferon (IFN) and the expression of hundreds of IFN-stimulated genes, which suppress RABV replication and spread in astrocytes. Notably, lab-attenuated RABV replicates in a manner identical to that of wt RABV in MAVS−/− astrocytes. It was also found that lab-attenuated, but not wt, RABV induces the expression of inflammatory cytokines via the MAVS- p38/NF-κB signaling pathway. These inflammatory cytokines increase the blood–brain barrier permeability and thus enable immune cells and antibodies infiltrate the CNS parenchyma, resulting in RABV control and elimination. In contrast, wt RABV restricts dsRNA production and thus evades innate recognition by RIG-I/MDA5 in astrocytes, which could be one of the mechanisms by which wt RABV evades the host immune response in resident CNS cells. Our findings suggest that astrocytes play a critical role in limiting the replication of lab-attenuated RABV in the CNS.

Background: Genetic factors are the main cause of early miscarriage. This study aimed to investigate aneuploidy in spontaneous abortion by fluorescence in situ hybridization (FISH) using probes for 13, 16, 18, 21, 22, X and Y chromosomes. Methods: A total of 840 chorionic samples from spontaneous abortion were collected and examined by FISH. We analyzed the incidence and type of abnormal cases and sex ratio in the samples. We also analyzed the relationship between the rate of aneuploidy and parental age, the rate of aneuploidy between recurrent abortion and sporadic abortion, the difference in incidence of aneuploidy between samples from previous artificial abortion and those from no previous induced abortion. Results: A total of 832 samples were finally analyzed. 368 (44.23%) were abnormal, in which 84.24% (310/368) were aneuploidies and 15.76% (58/368) were polyploidies. The first was trisomy16 (121/310), followed by trisomy 22, and X monosomy. There was no significant difference in the rate of aneuploidy in the advanced maternal age group (≥35 years old) and young maternal age group (

Background: There are more than 300 genetic loci that have been found to be related to hereditary hearing impairment (HHI), including 92 causative genes for nonsyndromic hearing loss, among which 34 genes are related to autosomal dominant nonsyndromic HHI (ADNSHHI). Traditional linkage analysis and candidate gene sequencing are not effective at detecting the ADNSHHI, especially for the unconditional families that may have more than one pathogenic cause. This study identified two disease-causing genes TJP2 and GJB2 in a Chinese family with unconditional ADNSHHI. Methods: To decipher the genetic code of a Chinese family (family 686) with ADNSHHI, different gene screening techniques have been performed, including linkage analysis, candidate genes screening, high-throughput sequencing and Sanger sequencing. These techniques were done on samples obtained from this family over a period of 10 years. Results: We identified a pathogenic missense mutation, c. 2081G>A (p.G694E), in TJP2, a gene that plays a crucial role in apoptosis and age-related hearing loss (ARHL). The mutation was co-segregated in this pedigree in all, but not in the two patients who presented with different phenotypes from the other affected family members. In one of the two patients, we confirmed that the compound heterozygosity for p.Y136FNx01 and p.G45E in the GJB2 gene may account for the phenotype shown in this patient. Conclusions: We identified the co-occurrence of two genetic causes in family 686. The possible disease-causing missense mutation of TJP2 in family 686 presents an opportunity for further investigation into ARHL. It is necessary to combine various genes screening methods, especially for some unconventional cases.

Rod gear speed reducer and transmission is composed of linkage mechanism and meshing transmission. This transmission mechanism is simplified plane four-bar mechanism. On the basis of kinematics and geometry principle,the kinematics analysis of the mechanism is studied by means of matrix method. The corresponding kinematics equations are derived,including position,velocity and acceleration equations of rod and rockers. The computer simulation analysis is developed and the variation curve of main component angle displacement,angle velocity,angle acceleration and errors are figured by using MATLAB program language. This study laid a foundation for further analysis and optimization of the rod gear speed reducer and transmission.