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The estimation of soil moisture (SM) utilizing the data from the Cyclone Global Navigation Satellite System (CYGNSS) has attracted significant interest in recent times. However, CYGNSS’ inherent capability of variable resolution has not been fully exploited, often resulting in a loss of detailed spatial information in the raw data. In this paper, a novel downscaling scheme tailored for CYGNSS data is introduced to yield a “self-adjusting adaptive resolution” SM product, which dynamically varies the resolution of SM estimates based on the available CYGNSS data resolution at different geographic locations. Initially, a direct quantitative relationship is established between the key CYGNSS parameters reflecting SM variations and the reference SM from the Soil Moisture Active Passive (SMAP) mission with a coarse resolution of 36 km. This model is then applied to CYGNSS observations with resolutions down to 3 km to generate high-resolution, self-adjusting SM estimates that better conserve the fine-scale information linked to the original CYGNSS data. Extensive experimental results with error ratio diagrams show that the advanced geographically weighted regression (GWR)-based SM estimation method outperforms other competing estimation models and better retains localized spatial relationships and patterns. This study underscores the potential of CYGNSS as a novel and robust independent data source capable of delivering fine-resolution SM estimations by harnessing its unique multiresolution observational capability.

Efficient solar energy utilization is a crucial determinant of crop yield formation. Moreover, various planting methods have dissimilar impacts on crop solar energy utilization and its measurement methods. This study examined the differences in solar energy utilization between monoculture and intercropping by considering density configuration, plant type arrangement, timing schedule, and spatial layout. We further evaluated the traditional methodologies versus remote sensing technology for solar energy measurements and described the differences in calculation methods for monoculture and intercropping, drawing from the photosynthesis model. Additionally, we discussed the potential advantages and limitations of employing remote sensing technology for the monitoring and prediction of solar energy utilization in field crops.

Given the ever-growing availability of remote sensing data (e.g., Gaofen in China, Sentinel in the EU, and Landsat in the USA), multimodal remote sensing techniques have been garnering increasing attention and have made extraordinary progress in various Earth observation (EO)-related tasks. The data acquired by different platforms can provide diverse and complementary information. The joint exploitation of multimodal remote sensing has been proven effective in improving the existing methods of land-use/land-cover segmentation in urban environments. To boost technical breakthroughs and accelerate the development of EO applications across cities and regions, one important task is to build novel cross-city semantic segmentation models based on modern artificial intelligence technologies and emerging multimodal remote sensing data. This leads to the development of better semantic segmentation models with high transferability among different cities and regions. The Cross-City Semantic Segmentation contest is organized in conjunction with the 13th Workshop on Hyperspectral Image and Signal Processing: Evolution in Remote Sensing (WHISPERS).

Compared with patients who undergo renal and islet transplantation sequentially, simultaneous omentum intraomental bio-scaffold islet-kidney transplantation in patients with type 1 diabetes complicated by renal failure has the advantages of donor homologation, less trauma, lower cost, and easier acceptance by patients. Omentum intraomental bio-scaffold islet has been gradually applied in clinical practice, and rare clinical complications have been reported. Here we report a case of abdominal abscess associated with extended-spectrum β-lactamase in a patient who underwent simultaneous omentum intraomental bio-scaffold islet-kidney transplantation; the islet grafts remained partially functional after appropriate anti-infective treatment.

Abstract The FK506-binding protein 51 (FKBP51, encoded by FKBP5 gene) has emerged as a critical regulator of mammalian endocrine stress responses and as a potential pharmacological target for metabolic disorders, including type 2 diabetes (T2D). However, in β cells, which secrete the only glucose-lowering hormone—insulin, the expression and function of FKBP5 has not been documented. Here, using human pancreatic tissue and primary human islets, we demonstrated the abundant expression of FKBP5 in β cells, which displayed an responsive induction upon acute inflammatory stress mimicked by in vitro treatment with a cocktail of inflammatory cytokines (IL-1β, IFN-γ, and TNF-α). To explore its function, siRNAs targeting FKBP5 and pharmacological inhibitor SAFit2 were applied both in clonal NIT-1 cells and primary human/mice islets. We found that FKBP5 inhibition promoted β-cell survival, improved insulin secretion, and upregulated β-cell functional gene expressions (MAFA and NKX6.1) in acute-inflammation stressed β cells. In primary human and mice islets, which constitutively suffer from inflammation stress during isolation and culture, FKBP5 inhibition also presented decent performance in improving islet function, in accordance with its protective effect against inflammation. Molecular studies found that FKBP5 is an important regulator for FOXO1 phosphorylation at Serine 256, and silencing of FOXO1 abrogated the protective effect of FKBP5 inhibition, suggesting that it is the key downstream effector of FKBP5 in β cells. At last, in situ detection of FKBP5 protein expression on human and mice pancreases revealed a reduction of FKBP5 expression in β cells in human T2D patients, as well as T2D mice model (db/db), which may indicate a FKBP5-inhibition-mediated pro-survival mechanism against the complex stresses in T2D milieus.

Abstract In mammals, the production of mature oocytes necessitates rigorous regulation of the discontinuous meiotic cell-cycle progression at both the transcriptional and post-transcriptional levels. However, the factors underlying this sophisticated but explicit process remain largely unclear. Here we characterize the function of N-acetyltransferase 10 (Nat10), a writer for N4-acetylcytidine (ac4C) on RNA molecules, in mouse oocyte development. We provide genetic evidence that Nat10 is essential for oocyte meiotic prophase I progression, oocyte growth and maturation by sculpting the maternal transcriptome through timely degradation of poly(A) tail mRNAs. This is achieved through the ac4C deposition on the key CCR4-NOT complex transcripts. Importantly, we devise a method for examining the poly(A) tail length (PAT), termed Hairpin Adaptor-poly(A) tail length (HA-PAT), which outperforms conventional methods in terms of cost, sensitivity, and efficiency. In summary, these findings provide genetic evidence that unveils the indispensable role of maternal Nat10 in oocyte development.

ObjectiveZinc is an essential micronutrient that is critical for many physiological processes, including glucose metabolism, regulation of inflammation, and intestinal barrier function. Further, zinc dysregulation is associated with an increased risk of chronic inflammatory diseases such as type II diabetes, obesity, and inflammatory bowel disease. However, whether altered zinc status is a symptom or cause of disease onset remains unclear. Common symptoms of these three chronic diseases include the onset of increased intestinal permeability and zinc dyshomeostasis. The specific focus of this work is to investigate how dietary sources of intestinal permeability, such as high sucrose consumption, impact transporter-mediated zinc homeostasis and subsequent zinc-dependent physiology contributing to disease development.MethodWe used in vivo subchronic sucrose treatment, ex vivo intestinal organoid culture, and in vitro cell systems. We analyze the alterations in zinc metabolism and intestinal permeability and metabolic outcomes.ResultsWe found that subchronic sucrose treatment resulted in systemic changes in steady-state zinc distribution and increased 65Zn transport (blood-to-intestine) along with greater ZIP14 expression at the basolateral membrane of the intestine. Further, sucrose treatment enhanced cell survival of intestinal epithelial cells, activation of the EGFR-AKT-STAT3 pathway, and intestinal permeability.ConclusionOur work suggests that subchronic high sucrose consumption alters systemic and intestinal zinc homeostasis linking diet-induced changes in zinc homeostasis to the intestinal permeability and onset of precursors for chronic disease.

Human oocyte maturation arrest represents one of the severe conditions for female patients with primary infertility. However, the genetic factors underlying this human disease remain largely unknown. The spindle assembly checkpoint (SAC) is an intricate surveillance mechanism that ensures accurate segregation of chromosomes throughout cell cycles. Once the kinetochores of chromosomes are correctly attached to bipolar spindles and the SAC is satisfied, the MAD2L1BP, best known as p31comet, binds mitosis arrest deficient 2 (MAD2) and recruits the AAA+-ATPase TRIP13 to disassemble the mitotic checkpoint complex (MCC), leading to the cell-cycle progression. In this study, by whole-exome sequencing (WES), we identified homozygous and compound heterozygous MAD2L1BP variants in three families with female patients diagnosed with primary infertility owing to oocyte metaphase I (MI) arrest. Functional studies revealed that the protein variants resulting from the C-terminal truncation of MAD2L1BP lost their binding ability to MAD2. cRNA microinjection of full-length or truncated MAD2L1BP uncovered their discordant roles in driving the extrusion of polar body 1 (PB1) in mouse oocytes. Furthermore, the patient’s oocytes carrying the mutated MAD2L1BP resumed polar body extrusion (PBE) when rescued by microinjection of full-length MAD2L1BP cRNAs. Together, our studies identified and characterized novel biallelic variants in MAD2L1BP responsible for human oocyte maturation arrest at MI, and thus prompted new therapeutic avenues for curing female primary infertility.

To investigate the anti-obesity effect of a noni (Morinda citrifolia L.) fruit polysaccharide (NFP) and its potential mechanisms, 24 male C57BL/6J mice were randomly divided into three groups—normal control group, high-fat diet (HFD) group, and NFP-administration group and were gavaged once a day for 12 weeks. The body weights, serum lipid parameters, bile acid (BA)-related proteins, fecal BA, and cecal bacteria of the mice were obtained and analyzed. Results indicate that NFP supplementation (200 mg/kg·bw) reduced the body weight, energy intake, and serum and liver lipids of the HFD mice. Further studies found that NFP activated the hepatic and colonic farnesoid X receptor and increased the excretion of fecal-conjugated BAs, particularly tauro-alpha-muricholic acid and tauro-beta-muricholic acid. In addition, NFP modulated the intestinal microbiota and increased the relative abundance of Lactobacillus in the HFD mice. In conclusion, NFP modulated gut microbiota and improved BA metabolism, which may be the main mechanism behind NFP alleviation of fat accumulation and dyslipidemia in mice under HFD.

Software defect prediction (SDP) plays an important role in allocating testing resources and improving testing efficiency. Multi-source cross-project defect prediction (MSCPDP) based on transfer learning refers to transferring defect knowledge from multiple source projects to the target project. MSCPDP has drawn increasing attention from academic and industry communities, and some MSCPDP methods have been proposed. However, most existing MSCPDP models are not open-source. MSCPDPLab replicates nine state-of-the-art MSCPDP models with unified interface and integrates the processes of data loading, model training and testing, and performance evaluation (including 13 performance measures). This paper describes the toolbox’s functionalities and presents its ease of use.

Abstract Background Cryptococcosis is a major opportunistic invasive mycosis in immunocompromised patients, but it is also increasingly seen in immunocompetent patients. In the early stages of cryptococcosis, limitations of the detection method may hinder the diagnosis. A molecular diagnostic technique based on nucleic acid sequence-based amplification (NASBA) method was developed to fulfil the need for efficient diagnosis of cryptococcosis. Methods We compared the diagnostic performance of NASBA, PCR and cryptococcal antigen (CrAg) test (colloidal gold method) in clinical samples from 25 cryptococcosis patients (including 8 cryptococcal meningoencephalitis and 17 pulmonary cryptococcosis) who were categorized as proven cases (n = 10) and probable cases (n = 15) according to the revised EORTC/MSG definitions. 10 patients with non-Cryptococcus infection and 30 healthy individuals were categorized as control group. Results The lowest detection limit of NASBA was 10 CFU/mL, and RNA of non-target bacteria or fungi was not amplified. The sensitivity of NASBA, PCR and colloidal gold method was 92.00% (95% CI 72.50–98.60%), 64.00% (95% CI 42.62–81.29%), 100.00% (95% CI 83.42–100.00%), and the specificity was 95.00% (95% CI 81.79–99.13%), 80.00% (95% CI 63.86–90.39%) and 82.50% (95% CI 66.64–92.11%) respectively. The highest specificity (97.50%), accuracy (95.38%) and k value (0.90) were achieved when both NASBA and colloidal gold results were positive. Conclusions NASBA is a new alternative detection method for cryptococcosis which is both accurate and rapid without expensive equipment and specialised personnel. It may be used as a tool for confirming current infection as well as monitoring the effectiveness of antifungal treatment. The use of NASBA to detect Cryptococcus RNA in blood samples is of great significance for the diagnosis of pulmonary cryptococcosis. The combination of NASBA and colloidal gold can improve the diagnostic accuracy of cryptococcosis.

Male sterility is an ideal character for the female parent in commercial hybrid seed production in Chinese cabbages. We identified three allele male sterile mutants msm2-1/2/3 in progenies of ethyl methane sulfonate mutagenized Chinese cabbage. It was proved that their male sterilities were controlled by a same recessive nuclear gene. Cytological observation showed that the delayed tapetal programmed cell death (PCD) as well as the abnormal pollen exine and intine led to pollen abortion in these mutants. MutMap combined with KASP analyses showed that BraA10g019050.3C, a homologous gene of AtMS1 encoding a PHD-finger transcription factor and regulated pollen development, was the causal gene. A single-nucleotide mutation from G to A occurred at the 2443th base of BrMS1 in msm2-1 which results in premature termination of the PHD-finger protein translation; a single-nucleotide mutation from G to A existed at 1372th base in msm2-2 that makes for frameshift mutation; a single-nucleotide mutation from G to A distributed at 1887th base in msm2-3 which issues in the amino acid changed from Asp to Asn. The three allelic mutations in BrMS1 all led to the male sterile phenotype, which revealed its function in stamen development. Quantitative reverse transcription polymerase chain reaction analysis indicated that BrMS1 specially expressed in the anther at the early stage of pollen development and its expression level was higher in msm2-1/2/3 than that in the wild-type “FT.” BrMS1 was located at the nucleus and a length of 12 amino acid residues at the C-terminus had transcriptional activation activity. RNA-seq indicated that the mutation in BrMS1 affected the transcript level of genes related to the tapetum PCD and pollen wall formation, which brought out the pollen abortion. These male sterile mutants we developed provided a novel gene resource for hybrid breeding in Chinese cabbage.

Abstract Background NKX6.1 is a transcription factor for insulin, as well as a marker for β cell maturity. Abnormal NKX6.1 expression in β cells, such as translocation from the nucleus to cytoplasm or lost expression, has been shown as a marker for β cell dedifferentiation. Methods We obtained pancreatic sections from organ donors and immunofluorescence staining with NKX6.1 and insulin was performed to characterize NKX6.1 expression in subjects with or without type 2 diabetes mellitus (T2DM). Results Our results showed that cells with insulin expression but no nucleic NKX6.1 expression (NKX6.1Nuc-Ins+), and cells with cytoplasmic NKX6.1 expression but no insulin expression (NKX6.1cytIns−) were significantly increased in T2DM subjects and positively correlated with glycated hemoglobin (HbA1c), indicating the elevated β cell dedifferentiation with NKX6.1 inactivation in T2DM. To investigate whether β cell dedifferentiation has initiated in subjects with higher risks for T2DM, we next analyzed the association between β-cell dedifferentiation level in ND subjects with different ages, body mass index, and HbA1c. The results showed the absolute number and percentage of dedifferentiated β cells with NKX6.1 inactivation did not significantly change in subjects with advanced aging, obesity, or modest hyperglycemia, indicating that the β cell dedifferentiation might mainly occur after T2DM was diagnosed. Conclusion Our results suggested that NKX6.1 expression in β cells was changed in type 2 diabetic subjects, evidenced by significantly increased NKX6.1Nuc-Ins+ and NKX6.1cytIns− cells. This abnormality did not occur more frequently in subjects with a higher risk for T2DM, suggesting that β cell dedifferentiation might be secondary to the pathological changes in T2DM.

Background: Linezolid is one of the last lines of defence for Gram-positive bacteria, and the increasing emergence of linezolid-resistant enterococci (LRE) has become an important problem in nosocomial infections. Objectives: This study aimed to explore the mechanisms of linezolid resistance and analyse risk factors for the infection with LRE. Methods: The known resistance mechanisms of linezolid were detected by polymerase chain reaction (PCR). Clinical data of patients with LRE infection were collected from the electronic medical record system. Risk factors associated with LRE were determined by comparing two case groups (LRE group and linezolid-susceptible enterococci [LSE] group) with the control group (without enterococci infection) at a ratio of 1:1:2. Multivariate logistic regression models were used to evaluate independent risk factors for acquiring LRE and LSE. Results: A total of 85 (4.5%) LRE isolates were detected during a 5-year period. The main resistance mechanism was acquisition of the transferable gene optrA (98.8%), followed by the L4 protein mutation (37.7%) and L3 protein mutation (4.7%). In our study, 85 LRE cases, 85 LSE cases, and 170 controls were then enrolled; multivariable analyses indicated that transfer from another hospital (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.5–7.3; P = 0.004), malignant tumour (OR, 3.7; 95% CI, 1.6–8.8; P = 0.003), polymicrobial infection (OR, 12.2; 95% CI, 1.4–106.2; P = 0.023), and urinary tract infections (OR, 42.7; 95% CI, 11.4–159.3; P = 0.000) were independent predictors for acquiring LRE. In addition, polymicrobial infections (OR, 43.3; 95% CI, 14.1–132.8; P = 0.000), total length of hospital stay (≥30 days) (OR, 5.7; 95% CI, 1.9–17.3; P = 0.002) and exposure to glycopeptide (OR, 6.6; 95% CI, 1.1–38.8; P = 0.035) were independently associated with LSE infections. Conclusions: Proper antibiotic management programs and monitoring of patient risk factors are necessary to control LRE infections.

Curly kale (Brassica oleracea L. convar. acephala var. sabellica), the most common type of edible kale, characterized by providing rich nutrition and health care functions, is sought after and has been listed as top of the healthiest vegetables in recent trends, and has aroused the interest of breeders in cultivating new varieties. However, it usually takes more than six years to obtain a homozygous kale inbred line for commercial seed production through conventional breeding procedures due to its long growth and development period. The isolated microspore culture (IMC) technique could be a time-saving alternative method for producing doubled haploid (DH) lines that are genetically homozygous. In this study, we successfully utilize the efficient cytokinin thidiazuron (TDZ) to promote microspore embryogenesis and plant regeneration in two curly kale cultivars (‘Winterbor F2’ and ‘Starbor F2’). Compared with the control (0 mg/L TDZ), all tested TDZ concentrations (0.1, 0.2, 0.3, 0.4 mg/L) had no adverse effects on embryogenesis, and 0.2 mg/L TDZ had an optimal effect on embryo survival and plant regeneration of the two genotypes. For ‘Starbor F2’, 0.2 mg/L TDZ treatment achieved the highest embryogenesis rate (1.83-fold higher than the control group) and direct seeding rate (1.61-fold increase), and the lowest mortality rate. Likewise, 0.2 mg/L TDZ increased the embryogenesis rate of ‘Winterbor F2’ by 1.62 times, the direct seeding rate by 1.61 times, and the mortality rate fell to the lowest. A 1/2 Murashige and Skoog (MS) medium with 0.2 mg/L 1-Naphthaleneacetic acid (NAA) can significantly promote the rooting of the regenerated seedlings. These results provide new insights into the practical application of the IMC technique in shortening the breeding cycle of kale.

Amphioxus is a promising model organism for understanding the origin and evolution of vertebrates due to its basal phylogenetic position among chordates. We here compared the mutation efficacy and mutation type of tail tips and gametes of amphioxus founders injected with Cas9 protein and six different sgRNAs targeting five distinct genes, and revealed a strong correlation for mutation efficacy and a mild correlation for mutation type among the two tissues. In addition, we also observed a positive relationship between gene insertions observed in tail tips and gametes of amphioxus founders injected with Tol2 transposase and two different transgenic constructs. Finally, we showed that amphioxus larvae which had their tail tips cut at the 3–4 gill-slit stage were able to recover within 6 days and developed a normal number of gonads at the adult stage, and that F0 larvae carry similar mutation efficacy and type in the posterior end to that in the tail tips after their metamorphosis. Together, these findings suggest a great potential for obtaining valid amphioxus founders with desired mutations and transgenes at as early as the early larval stage, which will certainly speed up the generation of amphioxus mutants and transgenes and make it more cost- and labor-effective.

β cell dedifferentiation is a key mechanism for β cell dysfunction in type 2 diabetes mellitus (T2DM). Although it has been indicated in previous studies that β cell dedifferentiation could be induced by inflammation, the cytohistologic analyses of inflammation-induced β cell dedifferentiation in human islets is lacking. The present study aims to cytohistologically characterize the β cell dedifferentiation of human islets treated by proinflammatory cytokines Interleukin-1β/Tuman necrosis factor-α/Interferon-γ (IL-1β/TNF-α/IFN-γ), which is a frequently-used method to mimic the islet inflammation in previous studies. The loss of cytosolic FOXO1 expression, the loss of nucleic NKX6.1 expression, and the gain of ALDH1A3 expression in β cells are proclaimed as marking events for β cell dedifferentiation. Taking advantages of islets from organ donors and the immunofluorescence staining methods, the present study visualized the β cell dedifferentiation events marked by different markers, and quantified the frequency of each event as well. We successfully captured and described the characteristics of the differentiating/differentiated β cells. We found that dedifferentiated β cells were increased in the cytokines treated islets, evidenced by the increase of β cells with FOXO1 translocated to the nucleus (INS + FOXO nuc ), β cells with NKX6.1 exported from the nucleus (INS + NKX6.1 cyt ), and β cells loss of NKX6.1 expression (INS + NKX6.1 - ), and β cells with dual expression of insulin and progenitor marker ALDH1A3. Consistently, we found that proinflammatory cytokines IL-1β/TNF-α/IFN-γ treatment reduced the mRNA expression of key β cell markers, but elevated the expression of progenitor marker genes. This study gives the most direct evidence for inflammation-induced β cell dedifferentiation in human islets, and supports the concept that anti-inflammation treatments may facilitate alleviating the β cell dedifferentiation in human T2DM islets.

Vitamin D is synthesized in the skin following exposure to UVB radiation or is directly absorbed from the diet. Following hydroxylation in the liver and kidneys, vitamin D becomes its bioactive form, 1,25(OH)2D, which has been described to have potent immunomodulatory capacity. This review will focus on the effect of vitamin D in modulating the dysregulated immune system of autoimmune rheumatic diseases (ARD) patients across age, in particular in arthritis (rheumatoid arthritis and juvenile idiopathic arthritis), and systemic lupus erythematosus (with adult and juvenile onset). As well as delineating the impact of vitamin D on the innate and adaptive immune functions associated with each disease pathology, this review will also summarize and evaluate studies that link vitamin D status with disease prevalence, and supplementation studies that examine the potential benefits of vitamin D on disease outcomes. Exploring this evidence reveals that better designed randomized controlled studies are required to clarify the impact of vitamin D supplementation on ARD outcomes and general health. Considering the accessibility and affordability of vitamin D as a therapeutic option, there is a major unmet need for evidence-based treatment recommendations for the use of vitamin D in this patient population.

Background: Several studies have indicated that positive childhood experiences (PCEs) might have important protective effects on adulthood mental health. However, the instruments to assess PCEs are scarce. Objective: In this study, we assessed the validity and reliability of the Benevolent Childhood Experiences (BCEs) scale, a new instrument of PCEs, in a large sample of Chinese adults. Furthermore, we examined associations of PCEs with symptoms of posttraumatic stress disorder (PTSD) and depression, as well as, prosocial behaviours across different levels of trauma. Method: Participants were 6929 adults (33% male; mean age 38.04 years, SD = 7.81, ranging from 18 to 81.) recruited from Jiangxi and Hunan provinces in China. Self-administrated questionnaires were used to measure PCEs, childhood trauma, lifetime trauma, PTSD, depression, and prosocial behaviours. Multiple linear regression models were conducted to examine the interdependent and interactive effects of PCEs, lifetime trauma, childhood trauma on symptoms of PTSD and depression and prosocial behaviours. Results: In the current sample, the Cronbach’s α of the BCEs scale was 0.70. PCEs were not related to lifetime trauma, while modestly associated with childhood trauma, demonstrating excellent discriminant validity. PCEs were negatively correlated with severity of PTSD and depression, while positively correlated with prosocial behaviours, indicating good predictive validity. PCEs, lifetime trauma and childhood trauma were independently associated with severity of PTSD and depression and prosocial behaviours. Moreover, the interaction of PCEs and lifetime trauma negatively predicted severity of PTSD and depression, while the interaction of PCEs and childhood trauma negatively predicted prosocial behaviours. PCEs had a protective effect on PTSD and depression in high level of lifetime trauma, and showed a reduced positive effect on prosocial behaviours in high level of childhood trauma. Conclusions: The Chinese BCEs scale is a reliable and valid instrument. PCEs can buffer adversity and foster positive outcomes in adulthood.

Despite recent recognition of the ATP-binding cassette protein OptrA as an important mediator of linezolid resistance in Enterococcus faecalis worldwide, the mechanisms of optrA gene acquisition and transfer remain poorly understood. In this study, we performed comprehensive molecular and phenotypic profiling of 44 optrA-carrying E. faecalis clinical isolates with linezolid resistance. Pulse-field gel electrophoresis and DNA hybridization revealed the presence of optrA in the plasmid in 26 (59%) isolates and in the chromosome in 18 (41%) isolates. Conjugation experiments showed a successful transfer of optrA in 88.5% (23/26) of isolates carrying optrA in plasmids while no transfer occurred in any isolates carrying optrA in the chromosome (0/18). All 23 transconjugants exhibited in vitro resistance to linezolid and several other antibiotics and were confirmed to contain optrA and other resistance genes. Plasmid typing demonstrated a predominance (18/23,78%) of rep9–type plasmids (pCF10 prototype) known to be the best studied sex pheromone responsive plasmids. Full plasmid genome sequencing of one isolate revealed the presence of drug resistance genes (optrA and fexA) and multiple sex pheromone response genes in the same plasmid, which represents the first sex pheromone responsive plasmid carrying optrA from a clinical isolate. PCR-based genotyping revealed the presence of three key sex pheromone response genes (prgA, prgB, and prgC) in 23 optrA-carrying isolates. Finally, functional studies of these isolates by clumping induction assay detected different degrees of clumping in 17 isolates. Our analysis suggests that optrA-mediated linezolid resistance can be widely disseminated through sex pheromone plasmid transfer.

Traditional dental implant navigation systems (DINS) based on binocular stereo vision (BSV) have limitations, for example, weak anti-occlusion abilities, as well as problems with feature point mismatching. These shortcomings limit the operators’ operation scope, and the instruments may even cause damage to the adjacent important blood vessels, nerves, and other anatomical structures. Trinocular stereo vision (TSV) is introduced to DINS to improve the accuracy and safety of dental implants in this study. High positioning accuracy is provided by adding cameras. When one of the cameras is blocked, spatial positioning can still be achieved, and doctors can adjust to system tips; thus, the continuity and safety of the surgery is significantly improved. Some key technologies of DINS have also been updated. A bipolar line constraint algorithm based on TSV is proposed to eliminate the feature point mismatching problem. A reference template with active optical markers attached to the jaw measures head movement. A T-type template with active optical markers is used to obtain the position and direction of surgery instruments. The calibration algorithms of endpoint, axis, and drill are proposed for 3D display of the surgical instrument in real time. With the preoperative path planning of implant navigation software, implant surgery can be carried out. Phantom experiments are carried out based on the system to assess the feasibility and accuracy. The results show that the mean entry deviation, exit deviation, and angle deviation are 0.55 mm, 0.88 mm, and 2.23 degrees, respectively.

Background: A physiological hallmark of patients with type 2 diabetes mellitus (T2DM) is β cell dysfunction. Despite adequate treatment, it is an irreversible process that follows disease progression. Therefore, the development of novel therapies that restore β cell function is of utmost importance. Methods: This study aims to unveil the mechanistic action of mesenchymal stem cells (MSCs) by investigating its impact on isolated human T2DM islets ex vivo and in vivo. Findings: We propose that MSCs can attenuate β cell dysfunction by reversing β cell dedifferentiation in an IL-1Ra-mediated manner. In response to the elevated expression of proinflammatory cytokines in human T2DM islet cells, we observed that MSCs was activated to secret IL-1R antagonist (IL-1Ra) which acted on the inflammed islets and reversed β cell dedifferentiation, suggesting a crosstalk between MSCs and human T2DM islets. The co-transplantation of MSCs with human T2DM islets in diabetic SCID mice and intravenous infusion of MSCs in db/db mice revealed the reversal of β cell dedifferentiation and improved glycaemic control in the latter. Interpretation: This evidence highlights the potential of MSCs in future cell-based therapies regarding the amelioration of β cell dysfunction. Keywords: Mesenchymal stem cells, Type 2 diabetes mellitus, β cell dysfunction, Inflammation, β cell dedifferentiation

A high precision optical tracking system (OTS) based on near infrared (NIR) trinocular stereo vision (TSV) is presented in this paper. Compared with the traditional OTS on the basis of binocular stereo vision (BSV), hardware and software are improved. In the hardware aspect, a NIR TSV platform is built, and a new active tool is designed. Imaging markers of the tool are uniform and complete with large measurement angle (>60°). In the software aspect, the deployment of extra camera brings high computational complexity. To reduce the computational burden, a fast nearest neighbor feature point extraction algorithm (FNNF) is proposed. The proposed method increases the speed of feature points extraction by hundreds of times over the traditional pixel-by-pixel searching method. The modified NIR multi-camera calibration method and 3D reconstruction algorithm further improve the tracking accuracy. Experimental results show that the calibration accuracy of the NIR camera can reach 0.02%, positioning accuracy of markers can reach 0.0240 mm, and dynamic tracking accuracy can reach 0.0938 mm. OTS can be adopted in high-precision dynamic tracking.

Despite increasing reports of low-level linezolid-resistant enterococci worldwide, the mechanism of this resistance remains poorly understood. Previous transcriptome studies of low-level linezolid-resistant Enterococcus faecalis isolates have demonstrated a number of significantly up-regulated genes potentially involved in mediation of drug resistance. However, whether the transcriptome faithfully reflects the proteome remains unknown. In this study, we performed quantitative proteomics analysis of membrane proteins in an E. faecalis isolate (P10748) with low-level linezolid-resistance in comparison with two linezolid-susceptible strains 3138 and ATCC 29212, all of which have been previously investigated by whole transcriptome analysis. A total of 8,197 peptides associated with 1,170 proteins were identified in all three isolates with false discovery rate (FDR) at 1% and P < 0.05. There were 14 significantly up-regulated and 6 significantly down-regulated proteins in strain P10748 compared to strains 3138 and ATCC 29212, which were in general positively correlated with transcription levels revealed in previous transcriptome studies. Our analysis suggests that the low-level linezolid-resistance in E. faecalis is conferred primarily by the ATP-binding cassette protein OptrA through ribosomal protection and, possibly, also by the enterococcal surface protein (Esp) and other proteins through biofilm formation. The genetic transfer of optrA is potentially regulated by the surface exclusion protein Sea1, conjugal transfer protein TraB, replication protein RepA and XRE family transcription regulator protein. This report represents the first investigation of the mechanisms of linezolid-resistance in E. faecalis by a quantitative proteomics approach.

Background Busulfan is the most commonly used drug for the treatment of chronic myelogenous leukemia and pretreatment for hematopoietic stem cell transplantation, which can damage the reproductive and immune system. However, little is known about the protein expression profiling in busulfan treated testis.Methods This research studies the proteomics for busulfan-induced spermatogenesis disorder. The model of busulfan-induced mouse spermatogenesis disorder was subjected to label-free quantification proteomics analysis. Clustering heatmap, gene ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein interaction analyses were performed and validated by molecular experiments.Results The busulfan-treated mouse model showed abnormal testis morphology and reduced sperm number and testis weight. Testicular and sperm damage was most severe at 30 days after busulfan treatment. The busulfan-treated mouse testes were subjected to label-free quantification proteomics, which revealed 190 significantly downregulated proteins including lactate dehydrogenase A like 6B (LDHAL6B) and ubiquitin-specific protease 7 (USP7). In addition, the testis and spermatozoa in the epididymis progressively improved from 70 to 80 days after busulfan treatment, and that the testis weight and spermatozoa number gradually increased from 40 to 80 days after busulfan treatment. Western blotting revealed that LDHAL6B protein significantly increased at 10 days, decreased from 20 to 60 days, and then gradually elevated from 70 to 80 days after busulfan treatment.Conclusion We revealed 190 significantly downregulated proteins in busulfan-treated mouse testes at 30 days and indicated that 70 days is the cut-off point of spermatogenic recovery for busulfan-treated mouse testis, increasing our understanding of this reproductive disorder model. An increased understanding of busulfan’s toxic effect will help to prevent and treat reproductive diseases.