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Abstract The organosulfur compound dimethylsulfoniopropionate (DMSP) has key roles in stress protection, global carbon and sulfur cycling, chemotaxis, and is a major source of climate-active gases. Saltmarshes are global hotspots for DMSP cycling due to Spartina cordgrasses that produce exceptionally high concentrations of DMSP. Here, in Spartina anglica, we identify the plant genes that underpin high-level DMSP synthesis: methionine S-methyltransferase (MMT), S-methylmethionine decarboxylase (SDC) and DMSP-amine oxidase (DOX). Homologs of these enzymes are common in plants, but differences in expression and catalytic efficiency explain why S. anglica accumulates such high DMSP concentrations and other plants only accumulate low concentrations. Furthermore, DMSP accumulation in S. anglica is consistent with DMSP having a role in oxidative and osmotic stress protection. Importantly, administration of DMSP by root uptake or over-expression of Spartina DMSP synthesis genes confers plant tolerance to salinity and drought offering a route for future bioengineering for sustainable crop production.

AbstractObjective Stable luteal cell function is an important prerequisite for reproductive ability and embryonic development. However, luteal insufficiency seriously harms couples who have the desire to have a pregnancy, and the most important thing is that there is no complete solution. In addition, Vaspin has been shown to have regulatory effects on luteal cells, but the complex mechanisms involved have not been fully elucidated. Therefore, this study aimed to explore the effect of Vaspin on rat luteal cells and its mechanism.Methods Granulosa lutein cells separated from the ovary of female rats were incubated for 24h with gradient concentrations of Vaspin, and granulosa lutein cells incubated with 0.5% bovine serum albumin were used as controls. The proliferation, apoptosis, angiogenesis, progesterone (P4) and estradiol (E2) were detected by CCK-8, Anneixn-FITC/PI staining, angiogenesis experiment and ELISA. Western blot was applied to observe the expression levels of proteins related to cell proliferation, apoptosis, angiogenesis and MEK/MAPK signaling pathway.Results Compared with the Control group, Vaspin could significantly up-regulate the proliferation of granulosa lutein cells and reduce the apoptosis. Moreover, Vaspin promoted the angiogenesis of granulosa lutein cells and the production of P4 and E2 in a concentration-dependent manner. Furthermore, Vaspin up-regulated the CyclinD1, CyclinB1, Bcl2, VEGFA and FGF-2 expression in granulosa lutein cells, and down-regulated the level of Bax. Also, Vaspin increased the p-MEK1 and p-p38 levels.Conclusion Vaspin can up-regulate the proliferation and steroidogenesis of rat luteal cells and reduce apoptosis, which may be related to the influence of MEK/MAPK activity.

Abstract Background Hadal trenches (>6000 m) are the deepest oceanic regions on Earth and depocenters for organic materials. However, how these enigmatic microbial ecosystems are fueled is largely unknown, particularly the proportional importance of complex polysaccharides introduced through deposition from the photic surface waters above. In surface waters, Bacteroidetes are keystone taxa for the cycling of various algal-derived polysaccharides and the flux of carbon through the photic zone. However, their role in the hadal microbial loop is almost unknown. Results Here, culture-dependent and culture-independent methods were used to study the potential of Bacteroidetes to catabolize diverse polysaccharides in Mariana Trench waters. Compared to surface waters, the bathypelagic (1000–4000 m) and hadal (6000–10,500 m) waters harbored distinct Bacteroidetes communities, with Mesoflavibacter being enriched at ≥ 4000 m and Bacteroides and Provotella being enriched at 10,400–10,500 m. Moreover, these deep-sea communities possessed distinct gene pools encoding for carbohydrate active enzymes (CAZymes), suggesting different polysaccharide sources are utilised in these two zones. Compared to surface counterparts, deep-sea Bacteroidetes showed significant enrichment of CAZyme genes frequently organized into polysaccharide utilization loci (PULs) targeting algal/plant cell wall polysaccharides (i.e., hemicellulose and pectin), that were previously considered an ecological trait associated with terrestrial Bacteroidetes only. Using a hadal Mesoflavibacter isolate (MTRN7), functional validation of this unique genetic potential was demonstrated. MTRN7 could utilize pectic arabinans, typically associated with land plants and phototrophic algae, as the carbon source under simulated deep-sea conditions. Interestingly, a PUL we demonstrate is likely horizontally acquired from coastal/land Bacteroidetes was activated during growth on arabinan and experimentally shown to encode enzymes that hydrolyze arabinan at depth. Conclusions Our study implies that hadal Bacteroidetes exploit polysaccharides poorly utilized by surface populations via an expanded CAZyme gene pool. We propose that sinking cell wall debris produced in the photic zone can serve as an important carbon source for hadal heterotrophs and play a role in shaping their communities and metabolism. Video Abstract

One of the challenges posed by current antibacterial therapy is that the expanded and massive use of antibiotics endows bacteria with the ability to resist almost all kinds of antibiotics. Therefore, developing alternative strategies for efficient antibacterial treatment is urgently needed. Antibacterial gas therapy has attracted much attention in the past decade. Nitric oxide (NO), carbon monoxide (CO), sulfur dioxide (SO2), hydrogen sulfide (H2S), and hydrogen (H2) are not only known as endogenous signaling molecules, but also play critical roles in many pathological processes. These gases are considered as attractive bactericidal agents because they are able to kill bacteria, disperse biofilms, and promote bacteria-infected wound healing while avoiding resistance. In this review, we discuss the bactericidal properties of these gases, as well as the recent advances of gas-involving systems in antibacterial, antibiofilm, and wound treatment applications. Moreover, we summarize various gas donors utilized in antibacterial treatment. We hope this review will shed new light on the future design and applications of advanced antibacterial gas therapy.

ABSTRACT The Sansha Yongle Blue Hole (SYBH), the deepest blue hole in the world, is an excellent habitat for revealing biogeochemical cycles in the anaerobic environment. However, how sulfur cycling is mediated by microorganisms in the SYBH hasn’t been fully understood. In this study, the water layers of the SYBH were divided into oxic zone, hypoxic zone, anoxic zone I and II, and microbial-mediated sulfur cycling in the SYBH was comprehensively interpreted. The 16S rRNA genes/transcripts analyses showed that the microbial community structures associated with the sulfur cycling in each zone had distinctive features. Sulfur-oxidizing bacteria were mostly constituted by Gammaproteobacteria, Alphaproteobacteria, Campylobacterota, and Chlorobia above the anoxic zone I and sulfate-reducing bacteria were dominated by Desulfobacterota in anoxic zones. Metagenomic analyses showed that the sulfide-oxidation-related gene sqr and genes encoding the Sox system were mainly distributed in the anoxic zone I, while genes related to dissimilatory sulfate reduction and sulfur intermediate metabolite reduction were mainly distributed in the anoxic zone II, indicating different sulfur metabolic processes between these two zones. Moreover, sulfur-metabolism-related genes were identified in 81 metagenome-assembled genomes (MAGs), indicating a high diversity of microbial communities involved in sulfur cycling. Among them, three MAGs from the candidate phyla JdFR-76 and AABM5-125-24 with genes related to dissimilatory sulfate reduction exhibited distinctive metabolic features. Our results showed unique and novel microbial populations in the SYBH sulfur cycle correlated to the sharp redox gradients, revealing complex biogeochemical processes in this extreme environment. IMPORTANCE Oxygen-deficient regions in the global ocean are expanding rapidly and affect the growth, reproduction and ecological processes of marine organisms. The anaerobic water body of about 150 m in the Sansha Yongle Blue Hole (SYBH) provided a suitable environment to study the specific microbial metabolism in anaerobic seawater. Here, we found that the vertical distributions of the total and active communities of sulfur-oxidizing bacteria (SOB) and sulfate-reducing bacteria (SRB) were different in each water layer of the SYBH according to the dissolved oxygen content. Genes related to sulfur metabolism also showed distinct stratification characteristics. Furthermore, we have obtained diverse metagenome-assembled genomes, some of which exhibit special sulfur metabolic characteristics, especially candidate phyla JdFR-76 and AABM5-125-24 were identified as potential novel SRB. The results of this study will promote further understanding of the sulfur cycle in extreme environments, as well as the environmental adaptability of microorganisms in blue holes.

Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms. Fingolimod (FTY-720) is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities, and has recently attracted much attention for the treatment of ischemic cerebrovascular diseases. In the current research, the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia model. Our results revealed that FTY-720 markedly decreased infarct volume, promoted neurological function recovery, and weakened the blood-brain barrier permeability of ischemic rats. The protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein levels. These findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.

Lung cancer is one of the most devastating diseases worldwide with high incidence and mortality, and the incidence continues to rise. Metastasis is the leading cause of death in lung cancer patients, yet the molecular effectors underlying tumor dissemination remain poorly defined. Research findings in recent years confirmed primed microenvironment of future metastatic sites, called the pre‐metastatic niche, is a prerequisite for overt metastasis. Exosomes have recently emerged as important players in pre‐metastatic niche formation. Natural medicines have traditionally been rich sources of drug discovery. Some of them exhibit favorable anti-lung cancer activity. The review focused on the latest advances in the regulation of the pre‐metastatic niche formation in lung cancer by the contents of exosomes of representative natural medicines. Additionally, the mechanism of natural medicines was summarized in detail, which would provide new insights for anti-cancer new drug development.

Abstract N6-methyladenosine (m6A), the most prevalent epigenetic modification of RNA in mammals, has become a hot topic throughout recent years. m6A is involved with every links of the RNA fate, including RNA splicing, nuclear export, translation and stability. Due to the reversible and dynamic regulatory network composed of ‘writers’ (methylase), ‘erasers’ (demethylase) and ‘readers’ (m6A binding proteins), m6A has been deemed as an essential modulator in vast physiological and pathological processes. Previous studies have shown that aberrant expression and dysfunction of these regulators are implicated in diverse tumors, exemplified by hematological malignancies. However, we should hold a dialectic perspective towards the influence of m6A modification on leukemogenesis. Given that m6A itself is neither pro-oncogenic nor anti-oncogenic, whether the modifications promote hematological homeostasis or malignancies occurrence and progression is dependent on the specific targets it regulates. Ample evidence supports the role of m6A in maintaining normal hematopoiesis and leukemogenesis, thereby highlighting the therapeutic potential of intervention in m6A modification process for battling leukemia. In this review, we introduce the advances of m6A modification and summarize the biological functions of m6A in RNA metabolism. Then we discuss the significance of several well-studied m6A regulators in modulating normal and malignant hematopoiesis, with focus on the therapeutic potentials of targeting these regulators for battling hematopoietic malignancies.

Abstract Background Immune checkpoint inhibitors had a great effect in triple-negative breast cancer (TNBC); however, they benefited only a subset of patients, underscoring the need to co-target alternative pathways and select optimal patients. Herein, we investigated patient subpopulations more likely to benefit from immunotherapy and inform more effective combination regimens for TNBC patients. Methods We conducted exploratory analyses in the FUSCC cohort to characterize a novel patient selection method and actionable targets for TNBC immunotherapy. We investigated this in vivo and launched a phase 2 trial to assess the clinical value of such criteria and combination regimen. Furthermore, we collected clinicopathological and next-generation sequencing data to illustrate biomarkers for patient outcomes. Results CD8-positivity could identify an immunomodulatory subpopulation of TNBCs with higher possibilities to benefit from immunotherapy, and angiogenesis was an actionable target to facilitate checkpoint blockade. We conducted the phase II FUTURE-C-Plus trial to assess the feasibility of combining famitinib (an angiogenesis inhibitor), camrelizumab (a PD-1 monoclonal antibody) and chemotherapy in advanced immunomodulatory TNBC patients. Within 48 enrolled patients, the objective response rate was 81.3% (95% CI, 70.2–92.3), and the median progression-free survival was 13.6 months (95% CI, 8.4–18.8). No treatment-related deaths were reported. Patients with CD8- and/or PD-L1- positive tumors benefit more from this regimen. PKD1 somatic mutation indicates worse progression-free and overall survival. Conclusion This study confirms the efficacy and safety of the triplet regimen in immunomodulatory TNBC and reveals the potential of combining CD8, PD-L1 and somatic mutations to guide clinical decision-making and treatments. Trial registration ClinicalTrials.gov: NCT04129996 . Registered 11 October 2019.

Abstract Chemically manipulating bacterial surface structures, a cutting‐edge research direction in the biomedical field, predominantly relies on metabolic labeling by now. However, this method may involve daunting precursor synthesis and only labels nascent surface structures. Here, we report a facile and rapid modification strategy based on a tyrosinase‐catalyzed oxidative coupling reaction (TyOCR) for bacterial surface engineering. This strategy employs phenol‐tagged small molecules and tyrosinase to initiate direct chemical modification of Gram‐positive bacterial cell walls with high labeling efficiency, while Gram‐negative bacteria are inert to this modification due to the hindrance of an outer membrane. By using the biotin‒avidin system, we further present the selective deposition of various materials, including photosensitizer, magnetic nanoparticle, and horseradish peroxidase, on Gram‐positive bacterial surfaces, and realize the purification/isolation/enrichment and naked‐eye detection of bacterial strains. This work demonstrates that TyOCR is a promising strategy for engineering live bacterial cells.

Dimethylsulfoniopropionate (DMSP) is an osmolyte produced by marine microbes that plays an important role in nutrient cycling and atmospheric chemistry. Here the authors go to the Mariana Trench—the deepest point in the ocean—and find bacteria are key DMSP producers, and that DMSP has a role in protection against high pressure.

Abstract Background Spontaneous subretinal hemorrhage (SSRH) is a rare disease that severely affects the visual function, and is difficult to diagnose. This study aimed to describe the multimodality imaging characteristics of SSRH in a young male patient. Case presentation A 28-year-old male was presented to our hospital with “sudden drop of left eye vision for one week.” Three weeks ago, he was admitted to other hospital due to sudden severe pain and unclear vision in the left eye for 1 h. The intraocular pressure was 69 mmHg, and the blood pressure was 230/120 mmHg. Skull CT and MRI detected abnormal signal shadows in the left eye and no abnormalities in the brain. B-ultrasonography indicated occupying lesions in the left eye. Two weeks later, the patient came to our hospital for treatment as the vision of the left eye had decreased sharply. Admission examination: blood pressure was 200/120 mmHg, best-corrected visual acuity was 20/20 in the right eye and hand motion in the left eye. Fundus details could not be evaluated in the left eye because of hemorrhage in the vitreous cavity. B-ultrasonography of the left eye revealed a dense, diffuse intravitreal hemorrhage. Skull MRI showed an abnormal signal shadow in the left eyeball, suggesting intraocular hemorrhage. Vitrectomy revealed a dome-shaped lesion in the peripheral part of the inferotemporal region during the operation. Postoperative indocyanine green angiography (ICGA) of the lesion showed hypofluorescence and no leakage or altered morphology during the whole imaging process. Follow-up showed gradual reabsorption of SSRH. Conclusions In this case, SSRH was considered to be associated with high blood pressure. Multimodal imaging provides accurate data for the diagnosis and follow-up of the disease.

Objective To evaluate the safety and efficacy of O‐arm‐guided minimally invasive pedicle screw fixation combined with percutaneous kyphoplasty for metastatic spinal tumors with posterior wall destruction. Methods Patients who underwent minimally invasive pedicle screw fixation combined with percutaneous kyphoplasty for pathological vertebral fractures with posterior wall defects from January 2015 to December 2017 were followed up for 1 year. Visual analogue scale (VAS), SF‐36 scores, middle vertebral height, posterior vertebral height, and the accuracy of pedicle screws were assessed preoperatively, postoperatively, and 1 year after surgery. The operation time, time from operation to discharge, blood loss, volume of bone cement, and leakage of bone cement were recorded. Results Twenty‐three patients (13 females and 10 males) who met our criteria were followed up for 1 year. The operation time of these patients was 162.61 ± 33.47 min, the amount of bleeding was 230.87 ± 93.76 mL, the time from operation to discharge was 4.35 ± 2.42 days, and the volume of bone cement was 3.67 ± 0.63 mL. The VAS score decreased from 7.04 ± 1.07 to 2.65 ± 0.93 before surgery (P = 0.000) and remained at 2.57 ± 0.79 1 year after surgery. Compared with the preoperative SF‐36 scores for physical pain, physiological function, energy, and social function, the postoperative scores were significantly improved (P = 0.000). The height of the middle vertebral body increased from 14.47 ± 2.96 mm before surgery to 20.18 ± 2.94 mm (P = 0.000), and remained at 20.44 to 3.01 mm 1 year after surgery. The height of the posterior vertebral body increased from 16.56 ± 3.07 mm before operation to 22.79 ± 4.00 mm (P = 0.000), and 22.45 ± 3.88 mm 1 year after surgery. The 23 patients had a total of 92 pedicle screws; 85 screws were Grade A and 7 screws were Grade B. There was no leakage of bone cement after surgery. Conclusion In the short term, O‐arm‐guided minimally invasive pedicle screw fixation combined with kyphoplasty is safe and effective in the treatment of metastatic spinal tumors with posterior wall destruction.

Rapid and accurate differentiation between live and dead cells is highly desirable for the evaluation of cell viability. Here, we report the application of the orange-emitting sulfur-doped organosilica nanodots (S-OSiNDs) for ultrafast (30 s), ultrasensitive (1 μg/mL), and universal staining of the dead bacterial, fungal, and mammalian cells but not the live ones, which satisfies the requirements of a fluorescent probe that can specifically stain the dead cells. We further verify that the fluorescence distribution range of S-OSiNDs (which are distributed in cytoplasm and nucleus) is much larger than that of the commercial dead/fixed cell/tissue staining dye RedDot2 (which is distributed in the nucleus) in terms of dead mammalian cell staining, indicating that S-OSiNDs possess a better staining effect of dead cells than RedDot2. Overall, S-OSiNDs can be used as a robust fluorescent probe for ultrafast and accurate discrimination between dead and live cells at a single cell level, which may find a variety of applications in the biomedical field.

Metagenomics and metatranscriptomics are powerful methods to uncover key micro-organisms and processes driving biogeochemical cycling in natural ecosystems. Databases dedicated to depicting biogeochemical pathways (for example, metabolism of dimethylsulfoniopropionate (DMSP), which is an abundant organosulfur compound) from metagenomic/metatranscriptomic data are rarely seen. Additionally, a recognized normalization model to estimate the relative abundance and environmental importance of pathways from metagenomic and metatranscriptomic data has not been organized to date. These limitations impact the ability to accurately relate key microbial-driven biogeochemical processes to differences in environmental conditions. Thus, an easy-to-use, specialized tool that infers and visually compares the potential for biogeochemical processes, including DMSP cycling, is urgently required. To solve these issues, we developed DiTing, a tool wrapper to infer and compare biogeochemical pathways among a set of given metagenomic or metatranscriptomic reads in one step, based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) and a manually created DMSP cycling gene database. Accurate and specific formulae for over 100 pathways were developed to calculate their relative abundance. Output reports detail the relative abundance of biogeochemical pathways in both text and graphical format. DiTing was applied to simulated metagenomic data and resulted in consistent genetic features of simulated benchmark genomic data. Subsequently, when applied to natural metagenomic and metatranscriptomic data from hydrothermal vents and the Tara Ocean project, the functional profiles predicted by DiTing were correlated with environmental condition changes. DiTing can now be confidently applied to wider metagenomic and metatranscriptomic datasets, and it is available at https://github.com/xuechunxu/DiTing.

ABSTRACTWe report a recent (2018) gonorrhoeal urethritis caused by a multidrug-resistant Neisseria gonorrhoeae strain in China. The isolated N. gonorrhoeae strain from a male and female pair expressed high-level resistance to spectinomycin (SPC), azithromycin, and other antibiotics but was sensitive to ceftriaxone. The SPC high-level resistance (MIC = 2048 mg/L) was due to a small deletion in rspE that caused two amino acid changes in ribosomal protein S5.

Quorum sensing (QS) is a density-dependent communicating mechanism that allows bacteria to regulate a wide range of biogeochemical important processes and could be inhibited by quorum quenching (QQ). Increasing researches have demonstrated that QS can affect the degradation of particulate organic matter (POM) in the photic zone. However, knowledge of the diversity and variation of microbial QS and QQ systems in sinking POM is scarce. Here, POM samples were collected from surface seawater (SW), bottom seawater (BW), and surficial sediment (SS) in the Yellow Sea of China. 16S rRNA gene amplicon and metagenome sequencing were performed to analyze the community structure of particle-associated microorganisms and distribution of QS genes [acylated homoserine lactone (AHL) synthesizing gene luxI and AHL sensing gene luxR] and QQ genes (genes encoding for AHL lactonase and acylase) in POM. Shifting community structures were observed at different sampling depths, with an increase of microbial abundance and diversity from SW to BW. Along with the variation of microbial communities, the abundances of luxI and luxR decreased slightly but were restored or even exceeded when POM arrived at SS. Comparatively, abundances of AHL lactonase and acylase remained constant during the transportation process from SW to BW but increased dramatically in SS. Correlation tests indicated that abundances of luxI and luxR were positively correlated with temperature, while those of AHL acylase were positively correlated with depth, SiO42–, PO43–, and NO3–, but negatively correlated with temperature and pH. According to phylogenetic analyses, the retrieved QS and QQ genes are more diverse and distinctive than ever experimentally identified. Besides, the vertical transmission of QS and QQ genes along with POM sinking was observed, which could be one of the key factors leading to the prevalence of QS and QQ genes in marine ecosystems. Overall, our results increase the current knowledge of QS and QQ metabolic pathways in marine environment and shed light on the intertwined interspecies relationships to better investigate their dynamics and ecological roles in POM cycling.

Microbial eukaryotes are widespread and play important roles in marine ecosystems. However, their ecological characteristics in the deep sea (>1,000 m), especially hadal trenches, were largely unknown. Here, we investigated the diversity and metabolic potentials of microbial eukaryotes along the whole water column of the Mariana Trench by metagenomics. Our results showed clear depth-related distribution of microbial eukaryotic community and associated metabolic potentials. Surface seawater was dominated by phototrophic/mixotrophic groups (e.g., Dinoflagellata) and genes involved in biosynthesis (photosynthesis and fatty acid biosynthesis), while deep (bathypelagic and/or hadal) seawaters were enriched with heterotrophic groups (e.g., Bicoecea) and genes related to digestion (lysosomal enzymes and V-type ATPase) and carbohydrate metabolism. Co-occurrence analysis revealed high intra-domain connectivity, indicating that microbial eukaryotic composition was more influenced by microbial eukaryotes themselves than bacteria. Increased abundance of genes associated with unsaturated fatty acid biosynthesis likely plays a role in resisting high hydrostatic pressure. Top1 and hupB genes, responsible for the formation and stabilization of DNA structure, were unique and abundant in the hadal zone and thus may be helpful to stabilize DNA structure in the deep sea. Overall, our results provide insights into the distribution and potential adaptability of microbial eukaryotes in the hadal zone.

In 2016, we identified a ceftriaxone-resistant Neisseria gonorrhoeae isolate in China. The strain genotype was identical to the resistant clone FC428 that originated in Japan. Enhanced international collaborative surveillance programs are crucial to track the transmission of the ceftriaxone-resistant clones.

Abstract The mitochondrial genome (mt genome) provides important information for understanding molecular evolution and phylogenetics. As such, the two complete mt genomes of Ampelophaga rubiginosa and Rondotia menciana were sequenced and annotated. The two circular genomes of A. rubiginosa and R. menciana are 15,282 and 15,636 bp long, respectively, including 13 protein-coding genes (PCGs), two rRNA genes, 22 tRNA genes and an A + T-rich region. The nucleotide composition of the A. rubiginosa mt genome is A + T rich (81.5%) but is lower than that of R. menciana (82.2%). The AT skew is slightly positive and the GC skew is negative in these two mt genomes. Except for cox1, which started with CGA, all other 12PCGs started with ATN codons. The A + T-rich regions of A. rubiginosa and R. menciana were 399 bp and 604 bp long and consist of several features common to Bombycoidea insects. The order and orientation of A. rubiginosa and R. menciana mitogenomes with the order trnM-trnI-trnQ-nad2 is different from the ancestral insects in which trnM is located between trnQ and nad2 (trnI-trnQ-trnM-nad2). Phylogenetic analyses indicate that A. rubiginosa belongs in the Sphingidae family, and R. menciana belongs in the Bombycidae family.

The Earth’s oceans are a huge body of water with physicochemical properties and microbial community profiles that change with depth, which in turn influences their biogeochemical cycling potential. The differences between microbial communities and their functional potential in surface to hadopelagic water samples are only beginning to be explored. Here, we used metagenomics to investigate the microbial communities and their potential to drive biogeochemical cycling in seven different water layers down the vertical profile of the Challenger Deep (0–10,500 m) in the Mariana Trench, the deepest natural point in the Earth’s oceans. We recovered 726 metagenome-assembled genomes (MAGs) affiliated to 27 phyla. Overall, biodiversity increased in line with increased depth. In addition, the genome size of MAGs at ≥4000 m layers was slightly larger compared to those at 0–2000 m. As expected, surface waters were the main source of primary production, predominantly from Cyanobacteria. Intriguingly, microbes conducting an unusual form of nitrogen metabolism were identified in the deepest waters (>10,000 m), as demonstrated by an enrichment of genes encoding proteins involved in dissimilatory nitrate to ammonia conversion (DNRA), nitrogen fixation and urea transport. These likely facilitate the survival of ammonia-oxidizing archaea α lineage, which are typically present in environments with a high ammonia concentration. In addition, the microbial potential for oxidative phosphorylation and the glyoxylate shunt was enhanced in >10,000 m waters. This study provides novel insights into how microbial communities and their genetic potential for biogeochemical cycling differs through the Challenger deep water column, and into the unique adaptive lifestyle of microbes in the Earth’s deepest seawater.

BACKGROUND:Gonorrhea remains one of the most common sexually transmitted diseases worldwide. Successful treatment has been hampered by emerging resistance to each of the antibiotics recommended as first-line therapies. We retrospectively analyzed the susceptibility of gonorrhea to azithromycin and ceftriaxone using data from the China Gonococcal Resistance Surveillance Programme (China-GRSP) in order to provide evidence for updating the treatment recommendations in China. METHODS AND FINDINGS:In this study, we included 3,849 isolates collected from patients with a confirmed positive Neisseria gonorrhoeae (N. gonorrhoeae) culture at clinic visits during the period of 1 January 2013 through 31 December 2016 in 7 provinces. Antimicrobial susceptibility testing of gonorrhea isolates using agar dilution was conducted to determine minimum inhibitory concentration (MIC). Resistance to azithromycin (RTA) was defined as MIC ≥ 1.0 mg/l, and decreased susceptibility to ceftriaxone (DSC) was defined as MIC ≥ 0.125 mg/l. The prevalence of isolates with RTA was 18.6% (710/3,827; 95% CI 17.4%-19.8%). The percentage of patients with DSC fluctuated between 9.7% and 12.2% over this period. The overall prevalence of isolates with both RTA and DSC was 2.3% (87/3,827; 95% CI 1.9%-2.8%) and it increased from 1.9% in 2013 to 3.3% in 2016 (chi-squared test for trend, P = 0.03). Study limitations include the retrospective study design and potential biases in the sample, which may overrepresent men with symptomatic infection, coastal residents, and people reporting as heterosexual. CONCLUSIONS:To our knowledge, this is the first national study on susceptibility of N. gonorrhoeae to azithromycin and ceftriaxone in China. Our findings indicate high rates of RTA and DSC from 2013 to 2016. Although dual therapy with azithromycin and ceftriaxone has been recommended by WHO and many countries to treat gonorrhea, reevaluation of this therapy is needed prior to its introduction in China.

AIM:To investigate efficacy of phacoemulsification combined with trabeculectomy for senile with cataract and glaucoma and to study the cause and the treatment for complications after the surgeries. METHODS: This study retrospectively analyzed 35 patients(42 eyes)with cataract and glaucoma treated by phacoemulsification combined with trabeculectomy. Visual acuity, anterior chamber depth,the change of the intraocular pressure(IOP)were observed before and after operations. Postoperative complications were observed and treated too. Follow-ups lasted for 6～18mo. RESULTS:Visual acuity of all patients had been improved with different degrees. The best corrected visual acuity(BCVA)was 0.3 in 22 eyes(52%). The mean IOP reduced from 23.24±6.89 mmHg before operations to 16.54 ± 2.56mmHg after operations. Anterior chamber depth increased from 1.34±0.41mm to 2.81±0.53mmHg after operations. About complications, there were 14 eyes with corneal edema, 2 eyes with fibrinoid exudation, 2 eyes with anterior chamber hemorrhage; 1 eyes with shallow anterior chamber and low intraocular pressure, 2 eyes with posterior capsule opacification, 3 eyes with high IOP. After the treatment for complications, the patients were satisfied with the operation efficacy.CONCLUSION:Phacoemulsification combined with trabeculectomy is safe and effective on the treatment of cataract coexisting with glaucoma, making little damage and quick healing. However, due to shallower anterior segment in glaucoma patients, phacoemulsification is difficult to performance. How to avoid the occurrence of complications and to treat them are the guarantee for successful operation.

In the current study, corn steep liquor (CSL) is evaluated as an ideal raw agro-material for efficient lipid and docosahexaenoic acid DHA production by Aurantiochytrium sp. Low CSL level in medium (nitrogen deficiency) stimulated the biosynthesis of lipids and DHA while inhibiting cellular growth. The transcriptomic profiles of the Aurantiochytrium sp. cells are analyzed and compared when cultured under high (H group), normal (N group), and low (L group) levels of CSL in the medium. The discriminated transcriptomic profiles from the three groups indicates that changes in CSL level in medium result in a global change in transcriptome of Aurantiochytrium sp. The overall de novo assembly of cDNA sequence data generated 61,163 unigenes, and 18,129 of them were annotated in at least one database. A total of 5105 differently expressed (DE) genes were found in the N group versus the H group, with 2218 downregulated and 2887 upregulated. A total of 3625 DE genes were found in the N group versus the L group, with 1904 downregulated and 1721 upregulated. The analysis and categorization of the DE genes indicates that the regulation mechanism of CSL involved in the perception and transduction of the limited nitrogen signal, the interactions between the transcription factors (TFs) and multiple downstream genes, and the variations in downstream genes and metabolites, in sequence, are illuminated for the first time in the current study.

Abstract Background Lymphatic metastasis is the major challenge in the treatment of penile cancer. The prognosis of individuals with lymphatic metastasis is extremely poor. Therefore, early identification of disease progression and lymphatic metastasis is an urgent task for researchers in penile cancer worldwide. Methods In this study, using single‐cell RNA sequencing, an immune landscape was established for the cancer ecosystem based on 46,861 cells from six patients with penile cancer (four with lymphatic metastasis [stage IV] and two without lymphatic metastasis [stage I]). Using bulk RNA sequencing, the discrepancy between the cancers and their respective metastatic lymph nodes was depicted based on seven patients with penile cancer. Results The interaction between epithelial cells, fibroblasts, and endothelial cells, and the functional cooperation among invasion, epithelial‐mesenchymal transition, and angiogenesis were found to be important landscapes in the penile cancer ecosystem, playing important roles in progression of cancer and lymph node metastasis. Conclusions This study is the first to investigate the altered tumor microenvironment heterogeneity of penile cancer as it evolves from non‐lymphatic to lymphatic metastasis and provides insights into the mechanisms underlying malignant progression, the premetastatic niche, and lymphatic metastasis in penile cancer.

Penile cancer is a rare malignant tumor of the male urinary system. The treatment benefit of standard first-line chemotherapy is not ideal for patients with locally advanced or metastatic lymph nodes. Immunotherapy has brought new treatment strategies and opportunities for patients with penile cancer. At present, clinical studies on immunotherapy for penile cancer have been reported, and the results show that it is effective but not conclusive. With the development of immunotherapy and the progress of molecular research technology, we can better screen the immunotherapy response population and explore new combination treatment regimens to evaluate the best combination regimen and obtain the optimal treatment options, which is also an important research direction for the immunotherapy of penile cancer in the future.