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Parabacteroides distasonis (P. distasonis), part of the gut microbiome, was reported to play a role in diabetes, colorectal cancer and inflammatory bowel disease. Here the authors report that P. distasonis ameliorates liver fibrosis in studies with male mice, potentially via altered bile acid metabolism and hepatocyte pyroptosis.

Parathyroid hormone-related protein (PTHrP) plays a significant role in various tumor types, including prostate cancer. However, its specific role and underlying mechanisms in prostate cancer remain unclear. This study investigates the role of PTHrP and its interaction with the c-Met in prostate cancer. PTHrP was overexpressed and knocked down in prostate cancer cell lines to determine its effect on cell functions. Xenograft tumor models were employed to assess the impact of PTHrP overexpression on tumor growth. To delve into the interaction between PTHrP and c-Met, rescue experiments were conducted. Clinical data and tissue samples from prostate cancer patients were gathered and analyzed for PTHrP and c-Met expression. PTHrP overexpression in prostate cancer cells upregulates c-Met expression and augments cell functions. In contrast, PTHrP-knockdown diminishes c-Met expression and inhibits cell functions. In vivo experiments further demonstrated that PTHrP overexpression promoted tumor growth in xenograft models.Moreover, modulating c-Met expression in rescue experiments led to concurrent alterations in prostate cancer cell functions. Immunohistochemical analysis of clinical samples displayed a significant positive correlation between PTHrP and c-Met expression. Additionally, PTHrP expression correlated with clinical parameters like prostate-specific antigen (PSA) levels, tumor stage, lymph node involvement, distant metastasis, and Gleason score. PTHrP plays a crucial role in prostate cancer progression by upregulating c-Met expression. These insights point to PTHrP as a promising potential biomarker for prostate cancer.

ABSTRACTMultidrug-resistant Klebsiella pneumoniae strains, especially carbapenem-resistant K. pneumoniae, have become a rapidly emerging crisis worldwide, greatly limiting current therapeutic options and posing new challenges to infection management. Therefore, it is imperative to develop novel and effective biological agents for the treatment of multidrug-resistant K. pneumoniae infections. Platelets play an important role in the development of inflammation and immune responses. The main component responsible for platelet antibacterial activity lies in the supernatant stimulated by gram-positive bacteria. However, little research has been conducted on the interaction of gram-negative bacteria with platelets. Therefore, we aimed to explore the bacteriostatic effect of the supernatant derived from platelet-K. pneumoniae coculture and the mechanism underlying this effect to further assess the potential of platelet-bacterial coculture supernatant. We conducted this study on the gram-negative bacteria K. pneumoniae and CRKP and detected turbidity changes in K. pneumoniae and CRKP cultures when grown with platelet-K. pneumoniae coculture supernatant added to the culture medium. We found that platelet-K. pneumoniae coculture supernatant significantly inhibited the growth of K. pneumoniae and CRKP in vitro. Furthermore, transfusion of platelet-K. pneumoniae coculture supernatant alleviated the symptoms of K. pneumoniae and CRKP infection in a murine model. Additionally, we observed apoptosis-like changes, such as phosphatidylserine exposure, chromosome condensation, DNA fragmentation, and overproduction of reactive oxygen species in K. pneumoniae following treatment with the supernatant. Our study demonstrates that the platelet-K. pneumoniae coculture supernatant can inhibit K. pneumoniae growth by inducing an apoptosis-like death, which is important for the antibacterial strategies development in the future.IMPORTANCEWith the widespread use of antibiotics, bacterial resistance is increasing, and a variety of multi-drug resistant Gram-negative bacteria have emerged, which brings great challenges to the treatment of infections caused by Gram-negative bacteria. Therefore, finding new strategies to inhibit Gram-negative bacteria and even multi-drug- resistant Gram-negative bacteria is crucial for treating infections caused by Gram-negative bacteria, improving the abuse of antibiotics, and maintaining the balance between bacteria and antibiotics. K. pneumoniae is a common clinical pathogen, and drug-resistant CRKP is increasingly difficult to cure, which brings great clinical challenges. In this study, we found that the platelet-K. pneumoniae coculture supernatant can inhibit K. pneumoniae growth by inducing an apoptosis-like death. This finding has inspired the development of future antimicrobial strategies, which are expected to improve the clinical treatment of Gram-negative bacteria and control the development of multidrug-resistant strains.

The distribution of species is mostly influenced by climate synergistic effects and land use. The prediction of endangered species is dependent on fine-scale environmental features, especially in forests. The capture of fine-scale suitable habitats is bounded by low spatial resolution and coarse categorization. In this study, we improved the land use information and forest spatial detail through high forest thematic resolution land use data. To understand the relative influence of environmental factors, suitable habitat models for Chinese endangered tree species (Firmiana danxiaensis) under three climate and high forest thematic resolution land use conditions was constructed. We also assess F. danxiaensis 's response to climate and land use, and differential performance in land use on the suitable habitat. The area of suitable habitat for F. danxiaensis grows slowly under the SSP1-2.6 (shared social pathway scenario) scenario, decreases by 21.33% from the present to 2090 under the SSP2-4.5 scenario, and expands significantly under the SSP5-8.5 scenario. We conclude that high forest thematic resolution land use is beneficial in capturing species' requirements for specific habitats and especially necessary in predicting endangered species. At the same time, the distribution of suitable habitats for species is primarily driven by climate, and limited their development by land use. The study shows that the synthetic effects of climate and land use change on F. danxiaensis are positive, with a marked trend toward the northeast. As a consequence, some endangered species are able to benefit from future SSPs scenarios, in particular they respond more strongly to the SSP5-8.5 scenario than to the other scenarios. Assessing the role of changes in the climate and high forest thematic resolution land use on F. danxiaensis will help promote sustainable land use management and contribute to the conservation policy for Chinese endangered species.

Asthma is a heterogeneous respiratory disease characterized by airway inflammation occurring in the bronchus. Direct delivery of targeted treatments to the bronchus for asthma has the potential to optimize therapeutic efficacy. Inhaled corticosteroids are cornerstone therapy for persistent asthma, however, there remain challenges in designing effective formulations for the inhaled route and minimizing long-term corticosteroid side effects. Here, a nanogel delivery system with good bio-adhesion based on alginate crosslinked with zinc ions was designed. The prepared alginate nanogel particles (ALG-NPs) effectively delivered icariin (ICA) which possesses anti-inflammatory and antioxidant activities, to the bronchus through ultrasonic aerosol inhalation, thereby ameliorating asthmatic symptoms and attenuating bronchial inflammation. The ALG-NPs exhibited favorable biological safety and could be deposited in the bronchus to control the release of ICA, enabling targeted treatment of asthma. In addition, ICA loaded ALG-NPs significantly reduced airway inflammation by modulating key targets associated with asthm (Th1 transcription factor and Th2 transcription factor) while also inducing eosinophilic apoptosis by regulating the Bax/Bcl-2 ratio expression. This study suggests that the ultrasonic aerosol inhalation of ICA loaded ALG-NPs was a promising strategy of treating asthma.

Background: Nintedanib and pirfenidone are preferred pharmacological therapies for patients with idiopathic pulmonary fibrosis (IPF). However, evidence favoring antifibrotic therapy in patients with non-IPF fibrosing interstitial lung diseases (ILD) is limited. Objective: To investigate the effects of antifibrotic therapy on disease progression, all-cause mortality, and acute exacerbation (AE) risk in patients with non-IPF fibrosing ILDs. Design: Meta-analysis. Data sources and methods: Electronic databases were searched for articles published before 28 February 2023. Studies that evaluated the efficacy of antifibrotic agents in patients with fibrosing ILDs were selected. The primary outcome was the disease progression risk, and the secondary outcomes included all-cause mortality and AE risk. The GRADE criteria were used for the certainty of evidence assessment. Results: Nine studies with 1990 participants were included. Antifibrotic therapy reduced the rate of patients with disease progression (five trials with 1741 subjects; relative risk (RR), 0.56; 95% CI, 0.42–0.75; p

Background: Litchi (Litchi chinensis) is an important sub-tropical fruit in the horticulture market in China. Breeding for improved fruit characteristics is needed for satisfying consumer demands. Budding is a sustainable method for its propagation. During our ongoing breeding program, we observed a litchi mutant with flat leaves and sharp fruit peel cracking in comparison to the curled leaves and blunt fruit peel cracking fruits of the mother plant.Methods: To understand the possible molecular pathways involved, we performed a combined metabolome and transcriptome analysis.Results: We identified 1,060 metabolites in litchi leaves and fruits, of which 106 and 101 were differentially accumulated between the leaves and fruits, respectively. The mutant leaves were richer in carbohydrates, nucleotides, and phenolic acids, while the mother plant was rich in most of the amino acids and derivatives, flavonoids, lipids and organic acids and derivatives, and vitamins. Contrastingly, mutant fruits had higher levels of amino acids and derivatives, carbohydrates and derivatives, and organic acids and derivatives. However, the mother plant’s fruits contained higher levels of flavonoids, scopoletin, amines, some amino acids and derivatives, benzamidine, carbohydrates and derivatives, and some organic acids and derivatives. The number of differentially expressed genes was consistent with the metabolome profiles. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway-enriched gene expressions showed consistent profiles as of metabolome analysis.Conclusion: These results provide the groundwork for breeding litchi for fruit and leaf traits that are useful for its taste and yield.

HuaChanSu is active water extracts from the skin of Bufo bufo gargarizans Cantor. It has been already used to treat clinical cancers including HCC (Hepatocellular carcinoma, HCC), however, the molecular mechanisms under HuaChanSu's anti-cancer effects remain unclear. PPP (Pentose phosphate pathway, PPP), the major source of ribose and NADPH (Nicotinamide adenine dinucleotide phosphate, NADPH), is always over-activated and particularly critical for tumor cells growth. In this study, firstly, we illustrate that HuaChanSu restrains the growth of human hepatoma cells. More importantly, we demonstrate that the expression of G6PD (Glucose-6-phosphate dehydrogenase, G6PD), the first rate-limiting enzyme of the PPP, is restrained in human hepatoma cells after treatment with HuaChanSu. Additionally, our results show that G6PD enzyme activity and dimer formation are inhibited by HuaChanSu. Furthermore, we find that HuaChanSu could inhibit NADPH production and nucleotide level. In addition, we identify that expression of PLK1 (Polo-like kinase 1, PLK1) is also reduced in response to HuaChanSu, and knockdown of PLK1 restrains enzyme activity and dimer formation of G6PD, but has no effect on G6PD protein level. Subsequently, we demonstrate that inhibition of G6PD could restrain the proliferation of tumor cells and enhance the inhibitory effect of HuaChanSu on cell proliferation of human hepatoma cells. In conclusion, for the first time, our study reveals that HuaChanSu interferes with PPP via suppression of G6PD expression and enzyme activity to restrain growth of tumor cells, and these results provide a novel insight for the anti-hepatoma mechanisms of HuaChanSu and promote the innovation of the research model of TCM. Moreover, the development of drugs targeting abnormal tumor metabolism is currently a hot topic, our works provide theoretical support for further drug development from HuaChanSu, meanwhile, the revelation of the new molecular mechanism also provides a new perspective for the study of the pathogenesis of liver cancer. Short abstract: HuaChanSu suppresses expression of G6PD, the first rate-limiting enzyme of the PPP, restrains G6PD enzyme activity and dimer formation via inhibition of PLK1, knockdown of G6PD could impair the growth of human hepatoma cells and increase the blocking effect of HuaChanSu on cell proliferation of cancer cells. In addition, HuaChanSu restrains NADPH production and nucleotide level, implying the suppression of PPP flux. Our study suggests that HuaChanSu interferes with PPP via G6PD inhibition to exert anti-hepatoma effects.

BackgroundBy comparing the three lateral approaches to thyroidectomy, the feasibility and clinical effects were analyzed, and the advantages of the lateral approach were summarized.MethodsFrom January 2022 to January 2023, 52 patients with thyroid cancer admitted to our department were selected and subjected to Lateral approach for thyroidectomy. Among them, 31 patients underwent thyroidectomy via the supraclavicular approach, 13 patients underwent endoscopic thyroidectomy via the subclavicular approach, and 8 patients underwent endoscopic thyroidectomy via the axillary approach. The basic conditions, surgical conditions, complications, postoperative pain scores and postoperative satisfaction of patients in the three approach surgery groups were recorded and analyzed.ResultsThere were no significant differences among the three approach groups in terms of patient characteristics, number of central lymph node dissections, intraoperative blood loss, postoperative drainage volume, duration of drainage tube placement, length of hospital stay, postoperative pain, satisfaction, and complications. However, the operation time was longest in the subclavicular approach group, followed by the axillary approach group, and shortest in the supraclavicular approach group. The total hospitalization cost was highest in the axillary approach group, followed by the subclavicular approach group, and lowest in the supraclavicular approach group.ConclusionThe lateral approach for thyroidectomy is deemed a safe and effective method. The three different approach paths gradually increase in length, allowing for the accumulation of anatomical experience. This approach has a shorter learning curve for clinical doctors and is a favorable choice for patients seeking aesthetic benefits.

Introduction: Diabetic ulcers have become one of the major complications of diabetes mellitus (DM) and are a leading cause of death and disabling disease. However, current therapies are not effective enough to meet clinical needs. A traditional Chinese medicine (TCM) formula, Pien Tze Huang (PZH), is known as a medicine that is used to treat diabetic ulcers.Methods: In this study, PZH (0.05 g/cm2 and 0.15 g/cm2) and the positive drug-rhEGF were topically administered in a high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic full-thickness incisional wounds, respectively. Wound healing was assessed by wound closure rate, two-photon microscope (SHG), staining with Hematoxylin and eosin (H&E), and Masson's trichrome (MTC). Then, RNA sequencing (RNA-seq) analysis, Enzyme-linked immunosorbent assay (ELISA), western blotting, and immunofluorescence (IF), network analysis, were performed.Results and discussion: The results showed that PZH significantly accelerated wound healing, as well as enhanced the expression of collagen. RNA-seq analysis showed that PZH has functions on various biological processes, one of the key biological processes is inflammatory response. Tlr9, Klrk1, Nod2, Tlr2, and Ifng were identified as vital targets and the NF-κB signaling pathway was identified as the vital pathway. Additionally, PZH profoundly reduced the levels of Cleaved caspase-3 and promoted the expression of CD31 and TGF-β1. Mechanically, PZH significantly decreased expression of NKG2-D, NOD2, and TLR2, and further inhibited the activation of downstream NF-κB signaling pathway and inhibited expression of inflammatory factors (IFN-γ and IL-1β). Importantly, we found that several active ingredients may play a significant role in diabetic wound healing, including Notoginsenoside R1, Deoxycorticosterone, Ursolic acid, and 4-Methoxyphenol. In summary, our study sheds light on the complicated mechanisms underlying the promising anti-diabetic wounds of PZH and provides the discovery of agents treating diabetic ulcers.

Study questionIn infertile women with polycystic ovary syndrome (PCOS), is the sequential use of letrozole 2.5 mg/follicle stimulating hormone(FSH) more effective than letrozole 5 mg/FSH in stimulating ovulation and promoting pregnancy?Research design and methodsThe study was designed as a prospective, single-center, randomized, controlled pragmatic clinical trial. 220 infertile women between the ages of 20 and 40, who matched the Rotterdam criteria for PCOS and had no other identified reasons for infertility were enrolled from April 2023 to July 2023.The participants were randomly assigned to two groups in a 1:1 ratio. One group received 2.5 mg of letrozole on cycle days 3-7 with a sequential injection of 75 IU FSH on cycle days 8-10 (n = 110), while the other group received 5 mg of letrozole on cycle days 3-7 with a sequential injection of 75 IU FSH on cycle days 8-10 (n = 110). The duration of FSH treatment varied depending on the follicular development stage. Each participant underwent one to three treatment cycles until achieving pregnancy.The primary outcome was the cumulative pregnancy rate of all the participants. Secondary outcomes included characteristics and clinical pregnancy rates of all the intervention cycles.ResultsFor all 220 participants, the sequential letrozole 2.5 mg/FSH treatment group had a significantly higher cumulative pregnancy rate compared to the letrozole 5 mg/FSH treatment group (72.7% versus 59.1%, RR (95%CI) = 1.23 (1.02, 1.49), P-value = 0.033). For all 468 intervention cycles, letrozole 2.5 mg/FSH group had a significantly higher clinical pregnancy rate than the letrozole 5 mg/FSH group (36.2% versus 26.3%, P-value = 0.021), no statistically significant differences were observed in ovulation rates or adverse effects.ConclusionsThe data indicate that the sequential letrozole 2.5mg/FSH protocol may be more effective than the sequential letrozole 5mg/FSH protocol for promoting pregnancy in infertile women with PCOS.Clinical trial registrationwww.chictr.org.cn, identifier ChiCTR2300069638.