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BackgroundSevere community-acquired pneumonia (SCAP) is the main cause of mortality in immunocompromised patients. Compared with conventional microbiological tests (CMT), metagenomic next-generation sequencing (mNGS) can quickly and simultaneously detect a wide array of bacteria, viruses, and fungi in an unbiased manner. It is increasingly used for severe respiratory infectious diseases, especially for immunocompromised patients. However, the effects of mNGS-based antimicrobial treatment procedures on clinical outcomes in immunocompromised patients with SCAP have not been evaluated.Methods/DesignThe MATESHIP study is a prospective, multicenter, parallel-group, open-label, randomized controlled trial from 20 ICUs in university hospitals and academic teaching hospitals across Shandong Province, China. We will enroll 342 immunocompromised patients with early onset SCAP who are admitted to an intensive care unit (ICU). Participants will be randomly allocated to an mNGS-guided treatment group or a conventional treatment group (guided by CMT), according to centrally computer-based block randomization stratified by participating centers. Participants will undergo CMT tests using appropriate lower respiratory tract (LRT) and other necessary specimens, with or without mNGS tests using LRT specimens. The primary outcomes will be: (1) The relative change in Sequential Organ Failure Assessment (SOFA) score from randomization to day 5, day 7, day 10, or the day of ICU discharge/death; and (2) the consumption of antimicrobial agents during ICU stay (expressed as defined daily doses). The secondary outcome measures will be: days from randomization to initiation of definitive antimicrobial treatment; overall antimicrobial agent use and cost; total cost of hospitalization; length of ICU stay; 28- and 90-day mortality; and clinical cure rate. This study hypothesizes that mNGS-guided treatment will decrease the degree of organ dysfunction/failure, the consumption of antimicrobial agents, and mortality, while the cure rate will be increased, and the time to initiation of appropriate therapy will be advanced.DiscussionThe MATESHIP study will evaluate for the first time whether mNGS-guided antimicrobial therapy improves the outcomes of SCAP in an immunocompromised population, and provide high-level evidence on the application of mNGS in the management of this population.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT05290454].

Context Qingluoyin (QLY) is a traditional Chinese medicine (TCM) formula which has been used in treating human rheumatoid arthritis (RA) for years in China. Objective This study investigates the effect of QLY granules on adjuvant arthritis (AA) and the possible mechanism. Materials and methods Sprague-Dawley (SD) rats were injected with Complete Freund’s adjuvant (CFA) to induce the AA model. After the onset of arthritis, rats received intragastric administrations of the QLY granules (1.35, 2.70, and 5.40 g/kg) or Tripterygium glycosides (TG) tablets (positive drug, 10 mg/kg) for 14 d. After 28 d immunization, the symptoms, inflammatory parameters and molecular mechanisms were investigated. Results In the QLY granule (1.35, 2.70, and 5.40 g/kg) therapy groups, the arthritis index decreased to 6.30 ± 2.06, 5.80 ± 1.55, 5.30 ± 1.16 compared with the model (9.00 ± 3.01), paw swelling decreased to 1.56 ± 0.40, 1.28 ± 0.38, 1.12 ± 0.41 mL compared with the model (2.22 ± 0.73 mL). QLY granules (1.35, 2.70 and 5.40 g/kg) significantly reduced the thymus and the spleen indexes, inhibited the production of pro-inflammatory cytokines, and alleviated the pathological changes of joints compared with the model group. Furthermore, the treatment of QLY granules (2.70 and 5.40 g/kg) markedly inhibited CXCL12, CXCR4 (in spleen and synovium) and p-NF-κB p65 (in synovium) protein expression of AA rats. Conclusions QLY granules have obvious therapeutic effects on AA rats, which may be associated with downregulating the CXCL12/CXCR4-NF-κB signalling pathway. QLY granules can be used as a candidate for the treatment of RA, which deserves further study.

Background. The present work aims at formulating the melatonin-loaded nanoparticles (MTNPs) exhibiting the controlled-release and pH-sensitivity to repurpose the use of melatonin in the treatment of depressive-like behaviors and hypothalamus-pituitary-adrenal (HPA) axis dysregulation. Methods. MTNPs were characterized for the size, drug incorporation, and in vitro release in the different pH environments. Its merits were in vivo tested on the pinealectomized rats presenting the depressive-like behaviors and the abnormal HPA axis activity by calculating the improvement on saccharin preference, swimming immobility time, and the negative feedback of HPA axis. Results. Results revealed that MTNPs showed nanometer size, 15.77% of drug loading, 33.82% of encapsulation efficiency, the different controlled-release profiles in different pH environments (pH 1.2, pH 6.8, and pH 7.4), more sensitivity release in simulated intestinal fluid (pH 7.4) and blood (pH 6.8), and less sensitivity release in simulated gastric fluid (pH 1.2). Furthermore, MTNPs displayed better antidepressant actions in reducing the immobility time of forced swimming test, increasing the preference for saccharin, and sensitizing the blunt negative feedback of HPA axis, when compared to the free melatonin. Conclusions. The controlled-release nanoparticles is shown to be an effective improvement on the dosage form for melatonin, which is worthy of futuristic and complete evaluation.

Aim. The aim of this study was to evaluate the levels of kisspeptin and AMH in children with PT or CPP or controls to provide a reference for diagnosis and prognosis. Methods. 38 Chinese children with central precocious puberty (CPP), 38 Chinese children with premature thelarche (PT), and 75 controls were recruited. Results. In CPP girls, AMH levels decreased significantly compared to control girls at T2 stage. Compared with the PT and control groups, AMH is the lowest in girls in the CPP group at T3 stage. Kisspeptin decreased significantly in girls in the PT group and increased significantly in girls in the control group from T2 stage to T3 stage. At T3 stage, kisspeptin was significantly higher in girls in the CPP and control groups than in the PT group. In the control group, kisspeptin was significantly higher in boys than in girls at T2 stage. AMH and height were negatively correlated in the girls group. Conclusions. Kisspeptin and AMH have a unique significance in the auxiliary diagnosis, the differential diagnosis, the treatment, and prognosis of sexual puberty disorder.

The synthesis of anthocyanin in pear (Pyrus bretschneideri) fruit is regulated by light. However, little is known about the molecular mechanisms of pear fruit coloring mediated by upstream light-signaling regulators. Here, the photoresponse factors CONSTITUTIVE PHOTOMORPHOGENIC (COP) 1.1 and 1.2 were cloned from ‘Red Zaosu’ peel to study their functions in pear fruit coloring. The overexpression vectors pBI121-PbCOP1.1 and pBI121-PbCOP1.2 were constructed to analyze their effects on anthocyanin synthesis in pear fruit. A protein sequence alignment and phylogenetic tree analysis revealed that PbCOP1 proteins are highly homologous with those of other species. An analysis of tissue differential expression showed that the greatest expression levels of PbCOP1s occurred in the leaves. Their expression levels increased in the leaves during development, when the leaves changed from red to green. The overexpression of PbCOP1s in the peel resulted in reduced anthocyanin synthesis at the injection sites. A quantitative PCR analysis of the injection sites showed that PbCOP1.1 significantly inhibited the expression of the anthocyanin synthesis-related genes CHI, DFR, UFGT2, bHLH3, HY5 and GST. Based on the above results, we hypothesize that PbCOP1.1 is an anthocyanin synthetic inhibitory factor of pear coloration.

Monitoring the quality of marine water is crucial for ensuring the health and sustainability of marine ecosystems. The conventional monitoring approach involves manual sampling using a water sampler, followed by packaging the water samples in plastic bottles and transporting them to a terrestrial laboratory for analysis. However, this method is time consuming, labor intensive, and cannot provide real-time data for addressing unforeseen circumstances. In response to these challenges, an advanced shipborne integrated platform for water quality inspection (ASIPWQI) has been proposed and implemented. This system automates the collection of multi-layer seawater samples in the vertical profile, conducts online measurements of monitoring elements, and provides real-time measurement data. In multiple sea trials, ASIPWQI successfully conducted onsite collection and measurement of a significant number of samples, meeting the water quality monitoring requirements in China’s nearshore waters. Comparative analysis of the laboratory measurement results for nutrients, heavy metals, and total phosphorus and nitrogen in water samples collected using automatic and manual methods revealed no significant differences between the two sampling approaches and demonstrated strong correlation. Further analysis using practical relative error (PRE) statistical methods showed that the data rate of most monitoring elements with relative errors less than 10% was higher than 70%, with nitrite, silicate, and phosphate even exceeding 90%. This indicate that ASIPWQI has excellent stability and applicability, offering a viable alternative to traditional manual sampling and laboratory testing. This innovation makes water quality monitoring significantly more efficient. [ABSTRACT FROM AUTHOR]