Identification of immune-related gene signatures for chronic obstructive pulmonary disease with metabolic syndrome: evidence from integrated bulk and single-cell RNA sequencing data.

Chronic obstructive pulmonary disease (COPD) is closely related to innate and adaptive inflammatory immune responses. It is increasingly becoming evident that metabolic syndrome (MetS) affects a significant portion of COPD patients. Through this investigation, we identify shared immune-related candidate biological markers. The Weighted Gene Co-Expression Network Analysis (WGCNA) was utilized to reveal the co-expression modules linked to COPD and MetS. The commonly expressed genes in the COPD and MetS were utilized to conduct an enrichment analysis. We adopted machine-learning to screen and validate hub genes. We also assessed the relationship between hub genes and immune cell infiltration in COPD and MetS, respectively. Moreover, associations across hub genes and metabolic pathways were also explored. Finally, we chose a single-cell RNA sequencing (scRNA-seq) dataset to investigate the hub genes and shared mechanisms at the level of the cells. We also applied cell trajectory analysis and cell-cell communication analysis to focus on the vital immune cell we were interested in. As a result, we selected and validated 13 shared hub genes for COPD and MetS. The enrichment analysis and immune infiltration analysis illustrated strong associations between hub genes and immunology. Additionally, we applied metabolic pathway enrichment analysis, indicating the significant role of reactive oxygen species (ROS) in COPD with MetS. Through scRNA-seq analysis, we found that ROS might accumulate the most in the alveolar macrophages. In conclusion, the 13 hub genes related to the immune response and metabolism may serve as diagnostic biomarkers and treatment targets of COPD with MetS.

The Genetic Echo of the Tarim Mummies in Modern Central Asians.

The diversity of Central Asians has been shaped by multiple migrations and cultural diffusion. Although ancient DNA studies have revealed the demographic changes of the Central Asian since the Bronze Age, the contribution of the ancient populations to the modern Central Asian remains opaque. Herein, we performed high-coverage sequencing of 131 whole genomes of Indo-European-speaking Tajik and Turkic-speaking Kyrgyz populations to explore their genomic diversity and admixture history. By integrating the ancient DNA data, we revealed more details of the origins and admixture history of Central Asians. We found that the major ancestry of present-day Tajik populations can be traced back to the admixture of the Bronze Age Bactria-Margiana Archaeological Complex and Andronovo-related populations. Highland Tajik populations further received additional gene flow from the Tarim mummies, an isolated ancient North Eurasian-related population. The West Eurasian ancestry of Kyrgyz is mainly derived from Historical Era populations in Xinjiang of China. Furthermore, the recent admixture signals detected in both Tajik and Kyrgyz are ascribed to the expansions of Eastern Steppe nomadic pastoralists during the Historical Era.

Structure and ecological function of the soil microbiome associated with 'Sanghuang' mushrooms suffering from fungal diseases.

BACKGROUND: The most serious challenges in medicinal 'Sanghuang' mushroom production are the fungal diseases caused by various molds. Application of biological agents has been regarded as a potential crop disease management strategy. Here, the soil microbiome associated with 'Sanghuang' mushroom affected by fungal diseases grown under field cultivation (FC) and hanging cultivation (HC) was characterized using culture-dependent and culture-independent methods. RESULTS: A total of 12,525 operational taxonomic units (OTUs) and 168 pure cultures were obtained using high-throughput sequencing and a culture-dependent method, respectively. From high-throughput sequencing, we found that HC samples had more OTUs, higher α-diversity, and greater microbial community complexity than FC samples. Analysis of ß-diversity divided the soil microbes into two groups according to cultivation mode. Basidiomycota (48.6%) and Ascomycota (46.5%) were the two dominant fungal phyla in FC samples, with the representative genera Trichoderma (56.3%), Coprinellus (29.4%) and Discosia (4.8%), while only the phylum Ascomycota (84.5%) was predominant in HC samples, with the representative genera Discosia (34.0%), Trichoderma (30.2%), Penicillium (14.9%), and Aspergillus (7.8%). Notably, Trichoderma was predominant in both the culture-independent and culture-dependent analyses, with Trichoderma sp. FZ0005 showing high host pathogenicity. Among the 87 culturable bacteria, 15 exhibited varying extents of antifungal activity against Trichoderma sp. FZ0005, with three strains of Bacillus spp. (HX0037, HX0016, and HX0039) showing outstanding antifungal capacity. CONCLUSIONS: Overall, our results suggest that Trichoderma is the major causal agent of 'Sanghuang' fungal diseases and that Bacillus strains may be used as biocontrol agents in 'Sanghuang' cultivation.

Anticancer Activity of Methyl Protodioscin against Prostate Cancer by Modulation of Cholesterol-Associated MAPK Signaling Pathway via FOXO1 Induction.

Methyl protodioscin (MPD), a furostanol saponin found in the rhizomes of Dioscoreaceae, has lipid-lowering and broad anticancer properties. However, the efficacy of MPD in treating prostate cancer remains unexplored. Therefore, the present study aimed to evaluate the anticancer activity and action mechanism of MPD in prostate cancer. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound healing, transwell, and flow cytometer assays revealed that MPD suppressed proliferation, migration, cell cycle, and invasion and induced apoptosis of DU145 cells. Mechanistically, MPD decreased cholesterol concentration in the cholesterol oxidase, peroxidase and 4-aminoantipyrine phenol (COD-PAP) assay, disrupting the lipid rafts as detected using immunofluorescence and immunoblot analyses after sucrose density gradient centrifugation. Further, it reduced the associated mitogen-activated protein kinase (MAPK) signaling pathway protein P-extracellular regulated protein kinase (ERK), detected using immunoblot analysis. Forkhead box O (FOXO)1, a tumor suppressor and critical factor controlling cholesterol metabolism, was predicted to be a direct target of MPD and induced by MPD. Notably, in vivo studies demonstrated that MPD significantly reduced tumor size, suppressed cholesterol concentration and the MAPK signaling pathway, and induced FOXO1 expression and apoptosis in tumor tissue in a subcutaneous mouse model. These results suggest that MPD displays anti-prostate cancer activity by inducing FOXO1 protein, reducing cholesterol concentration, and disrupting lipid rafts. Consequently, the reduced MAPK signaling pathway suppresses proliferation, migration, invasion, and cell cycle and induces apoptosis of prostate cancer cells.

First Report of Root Rot Caused by Pleiocarpon algeriense on peony (Paeonia suffruticosa) in China.

Peony (Paeonia suffruticosa Andr.) is a perennial plant of Ranunculaceae. Its root bark (Danpi in Chinese) is a traditional Chinese medicine, which has the effects of clearing heat and cooling blood, promoting blood circulation to resolve blood stasis. Peony is mainly planted in the provinces of Anhui, Gansu, Henan and Shandong. Peony is also called Fengdan in the Fenghuang Mountain of Tongling, Anhui Province. In November 2021, a root rot-like disease was observed on the root of peony in several fields located in Tongling county, Anhui Province, China (118°0'51" N, 30°48'11" E). Approximately 20-40% of the peony plants were affected in the fields. The roots of the diseased plants were rotten and blackened, the bark of the roots was detached, and the leaves were withered, causing the whole plants to die. To isolate the pathogen, the symptomatic roots were sampled, and small pieces (5 × 5 mm) of diseased tissues were surface sterilized with 0.5% NaClO solution and 75% ethanol for 5 min, rinsed with sterile distilled water three times, and finally incubated on potato dextrose agar (PDA) at 28°C in the dark for 7 days. A total of 16 isolates were obtained from the infected tissues. Among isolates, six isolates were morphologically similar to B4. Colonies were passaged multiple times on fresh PDA medium, and pure isolate B4 exhibiting cinnamon-to-honey coloration on PDA with pale yellow aerial hyphae, was then selected. Microscopic observations revealed that microconidia were straight to curved, ellipsoid or subcylindrical, and ranged from 7.14 to 14.29 × 2.85 to 5.00 µm (n = 20). The morphological characteristics were similar to the description of Pleiocarpon algeriense by Aigoun-Mouhous et al. (2019). To further identify the taxonomic status of B4 strain, three genes of the internal transcribed spacer (ITS) region of rDNA, beta-tubulin (TUB2), and the RNA polymerase II second subunit (RPB2) were respectively amplified and sequenced using primers ITS1/ITS4 (White et al. 1990), T1/Bt-2b (O'Donnell and Cigelnik 1997), and 5F2/7cR (O'Donnell et al. 2007). Sequences for the isolate B4 were deposited in GenBenk (OP810684, ITS; OP882301, TUB2; OP863337, RPB2). BLAST analysis showed the ITS, TUB2, RPB2 sequences of B4 were 99.80% (505/506), 99.51% (609/612) and 100.00% (854/854) homology with those of P. algeriense Di3A-AP52 (MT613337, ITS; MT597145, TUB2; MT635004, RPB2). A phylogenetic tree was built using MEGA11 based on sequences of three genes showing that B4 strain was closely clustered with reference strain of P. algeriense, which has not been reported in peony in China. The pathogenicity test of the isolates was performed by inoculating 50 mL of conidial suspension (1 × 108 conidia/mL) on the roots of ten healthy peonies, ten peonies inoculated with 50 mL of sterile water were used as a control group. After one-month, typical symptoms of root rot appeared on the inoculated plants and the control plants were asymptomatic. The fungus (P. algeriense) was reisolated from the diseased roots and identified by sequencing of ITS gene, conforming to Koch's postulates. Pleiocarpon algeriense has been reported to cause stem and crown rot in avocado (Aiello et al. 2020). To the best of our knowledge, this is the first report of P. algeriense causing root rot in peony. Control methods of P. algeriense on peony fields will be studied in-depth in the future.

Study on the Potential for Stimulating Mulberry Growth and Drought Tolerance of Plant Growth-Promoting Fungi.

Drought stress often leads to heavy losses in mulberry planting, especially for fruits and leaves. Application of plant growth-promoting fungi (PGPF) endows various plant beneficial traits to overcome adverse environmental conditions, but little is known about the effects on mulberry under drought stress. In the present study, we isolated 64 fungi from well-growing mulberry trees surviving periodical drought stress, and Talaromyces sp. GS1, Pseudeurotium sp. GRs12, Penicillium sp. GR19, and Trichoderma sp. GR21 were screened out due to their strong potential in plant growth promotion. Co-cultivation assay revealed that PGPF stimulated mulberry growth, exhibiting increased biomass and length of stems and roots. Exogenous application of PGPF could alter fungal community structures in the rhizosphere soils, wherein Talaromyces was obviously enhanced after inoculation of Talaromyces sp. GS1, and Peziza was increased in the other treatments. Moreover, PGPF could promote iron and phosphorus absorption of mulberry as well. Additionally, the mixed suspensions of PGPF induced the production of catalase, soluble sugar, and chlorophyll, which in turn enhanced the drought tolerance of mulberry and accelerated their growth recovery after drought. Collectively, these findings might provide new insights into improving mulberry drought tolerance and further boosting mulberry fruit yields by exploiting interactions between hosts and PGPF.

Roles of ARID1A variations in colorectal cancer: a collaborative review.

Colorectal cancer (CRC), a common malignancy, is one of the leading cause of cancer death in adults. AT-rich interaction domain 1A (ARID1A), a critical portion of the SWItch/sucrose non-fermentation (SWI/SNF) chromatin remodeling complexes, shows one of the most frequent mutant genes across different human cancer types. Deleterious variations of ARID1A has been recognized to be correlated the tumorigenesis and the poor prognosis of CRC. Here, we summarize recent advances in the clinical implications and molecular pathogenesis of ARID1A variations in CRC. According to independent data of 23 included studies, ARID1A is mutated in 3.6-66.7%. Consistently, all of the 23 relevant studies report that ARID1A functions as a specific tumor suppressor in CRC. Clinically, ARID1A variation status serves as a biomarker for survival prognosis and various therapies for CRC. Mechanistically, the pathophysiologic impacts of ARID1A variations on CRC may be associated with the co-occurrence variations of other genes (i.e., TP53, KRAS, APC, FBXW7, and PIK3CA) and the regulation of several signaling pathways being affected (i.e., WNT signaling, Akt signaling, and MEK/ERK pathway), leading to cell cycle arrest, chromatin remodeling, chromosome organization, and DNA hypermethylation of the cancer cells. The present review highlights ARID1A serving as a potent tumor suppressor and an important prognostic factor in CRC. ARID1A variations hint towards a promising tool for diagnostic tumor profiling and individualized therapeutic targets for CRC in the future.

Risk of osteoporosis and fracture after hysterectomies without oophorectomies: a systematic review and pooled analysis.

The present study provides evidence that women who underwent hysterectomy without oophorectomies are at a higher risk of osteoporosis and bone fractures than the general population. Early interventions for these susceptible women may help to delay or reduce the risk of osteoporosis and bone fractures. INTRODUCTION: Mounting studies have shown that patients with hysterectomy are at high risk of developing osteoporosis or bone fractures, but the evidence from all the relevant studies has not been previously synthesized. The present study aims to investigate whether women with hysterectomy without oophorectomies have a prominently higher prevalence of osteoporosis or fractures than healthy subjects. METHODS: Four electronic databases were systematically searched to identify the eligible studies. The combined effect was assessed by calculating the relative risk (RR) with a 95% confidence interval (CI). More methodologies for this study were available in the PROSPERO (ID: CRD42021227255). RESULTS: Finally, three observational studies offering osteoporosis cases and two retrospective studies reporting fracture cases were included. One eligible study has provided independent data from three groups of fractures. Synthetic results revealed that hysterectomy without oophorectomies was significantly associated with an increased risk of osteoporosis as compared to the general population (combined RR from three studies = 1.47, 95%CI 1.253 to 1.725, P < 0.001; heterogeneity, I2 = 76.2%, P = 0.015). Consistently, the prevalence of fractures was also significantly higher in patients with hysterectomy without oophorectomies than in healthy controls (pooled RR from four studies = 2.333, 95%CI: 1.314 to 4.144, P = 0.004; heterogeneity, I2 = 92.3%, P < 0.001). CONCLUSIONS: This is the first study to quantify the association between hysterectomy without oophorectomies and osteoporosis/fracture risk through a meta-analysis and has subsequently confirmed its positive relationship. Additional large-sample rigorously prospective cohorts are still warranted to validate the present evidence.

The impact of the endophytic bacterial community on mulberry tree growth in the Three Gorges Reservoir ecosystem, China.

Plant-associated microbes influence plant performance and may also impact biotic and abiotic stress tolerance. The microbiome of mulberry trees planted for ecological restoration in the hydro-fluctuation belt of the Three Gorges Reservoir Region, China, exhibited distinct patterns of localization. The endosphere exhibited lower α-diversity relative to the rhizosphere, but was more closely related to host growth status, especially in stem tissues. Pantoea was the predominant bacterial genus inhabiting the stems of two well-growing plants, while sequences identified as Pseudomonas and Pantoea were abundant in poorly growing plants. The complexity of the endophytic community was more connected to growth status in well-growing plants than it was in poorly growing plants. Among 151 endophytes cultured from collected samples of mulberry, 64 exhibited plant growth-promoting (PGP) potential in vitro and the majority of beneficial taxa were harvested from well-growing plants. Collectively, the present study indicates that the recruitment of beneficial endophytes may contribute to mulberry fitness under abiotic stress, and it provides a foundation for the development of a new strategy in vegetation restoration.

Hematologic and spirometric characteristics of Tajik and Kyrgyz highlanders in the Pamir Mountains.

OBJECTIVES: In this study, we measured the hematologic and spirometric parameters of native Tajik and Kyrgyz highlanders in the Pamir Mountains to investigate adaptations to high altitude stressors. METHODS: Hematological parameters including arterial oxygen saturation (SaO2 ), red blood cell (RBC) counts, and hemoglobin (Hb) concentration were measured on Sarikoli Tajik (n = 80; 3100 m), Wakhi Tajik (n = 48; 3500 m), and Kyrgyz (n = 64; 3250 m) in comparison to lowland Uyghurs (n = 50; 1300 m). Spirometric parameters including forced vital capacity (FVC), the first second of forced expiration (FEV1), and forced expiratory flow between 25% and 75% (FEF25-75) were measured. We also reported mountain sickness symptoms in these highlanders and conducted a multivariate regression analysis to analyze the association between these symptoms and the measured parameters. RESULTS: SaO2 of Sarikoli Tajik, Wakhi Tajik, and Kyrgyz (91%-93.5%) are significantly lower than lowland Uyghurs, yet are comparable to other native highlanders at a similar altitude. RBC counts and Hb concentrations of all three highland populations are significantly increased compared to Uyghurs. FVC is lower in Sarikoli Tajik, Wakhi Tajik, and Kyrgyz (male: 3.48-3.86 L, female: 2.47-2.78 L) compared to Uyghurs. Combined with normal FEV1, elevated FEV1/FVC ratio, and FEF25-75, the spirometric patterns of these highlanders indicate restrictive lung disease. A high prevalence of mountain sickness symptoms such as headache and nausea was found in all three highland populations, and are attributed to low FVC and aging by regression analysis. CONCLUSION: Tajik and Kyrgyz highlanders showed adaptation in SaO2 , RBC, and Hb level, but poor performance in spirometry, which causes mountain sickness.

The risk factors of postoperative delirium in patients with hip fracture: implication for clinical management.

BACKGROUND: Delirium is a common complication of hip surgery patients. It is necessary to investigate the epidemiological characteristics and related risk factors of delirium after hip fracture surgery, to provide evidence supports for the prevention and management of delirium. METHODS: Hip fracture patients admitted to our hospital for surgical treatment from March 2018 to March 2020 were identified as participants. The characteristics and laboratory examinations in patients with and without postoperative delirium were compared and analyzed. Logistic regression analyses were conducted to ascertain the independent risk factors, and the area under the curve (AUC) were calculated to analyze the predictive value. RESULTS: A total of 568 postoperative patients with hip fracture were included, the incidence of delirium in postoperative patients with hip fracture was 14.44 %. The preoperative albumin (OR 4.382, 2.501 ~ 5.538), history of delirium (OR 2.197, 1.094 ~ 3.253), TSH (OR1.245, 1.077 ~ 1.638), the resting score on the first postoperative day (OR1.235, 0.944 ~ 1.506) and age(OR1.185, 0.065 ~ 1.814) were the independent risk factors for the postoperative delirium in patients with hip fracture(all p < 0.05). The AUC of albumin, history of delirium, TSH, the resting score on the first postoperative day and age were 0.794, 0.754, 0.746, 0.721 and 0.689 respectively. CONCLUSIONS: The incidence of delirium in postoperative patients with hip fracture is rather high, especially for patients with old age and history of delirium. Monitoring albumin, TSH and resting score may be beneficial to the management of postoperative delirium.

Nonalcoholic fatty liver disease and risk of prostatic diseases: Roles of insulin resistance.

Nonalcoholic fatty liver disease (NAFLD), the liver component of metabolic syndrome, is considered to be associated with high risk of prostatic diseases but a systematic review has not been conducted. Under a comprehensive review of the eligible clinical studies, a potential positive association between NAFLD and benign prostatic hyperplasia/prostate cancer (BPH/PCa) has been postulated. Insulin resistance and metabolic aberrations are considered to be the potential mechanism for such association. However, the relationship between NAFLD and other prostatic diseases, that is, prostatic inflammation and lower urinary tract symptoms, seems vague due to limited relevant studies in the literatures. The present review highlights that clinicians should be conscious of the detrimental effect of NAFLD on the development of BPH and PCa.

Heparin sensitivity and postoperative blood loss in patients undergoing cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Heparin-associated coagulation disorder is an important factor related to postoperative bleeding in patients undergoing cardiac surgery with cardiopulmonary bypass. Currently, the relationship between heparin sensitivity and postoperative bleeding is unknown. OBJECTIVE: To investigate the relationship between individual heparin sensitivity and postoperative blood loss in patients undergoing cardiac surgery. DESIGN: Prospective controlled study. SETTING: Tertiary teaching hospital, Urumqi, Xinjiang, PR China. The study was conducted from January 2016 to August 2018. PATIENTS: A total of 195 adult patients undergoing cardiac valve replacement surgery were included. INTERVENTION: After initial heparin dosing (2.5 mg kg), patients were divided into three groups according to the whole blood activated clotting time (ACT): group A, insensitive group (ACT < 480 s); group B, sensitive group (480 s < ACT < 750 s); group C, hypersensitive group (ACT > 750 s). MAIN OUTCOME MEASURES: First, intra-operative and 24-h postoperative blood loss. Second, antithrombin (AT) and factor X mRNA levels. Third, the plasma levels of AT-III and factor X. Fourth, heparin sensitivity index. RESULTS: Blood loss was approximately 20 to 25% lower in group B than in groups A and C, which was statistically significant (P < 0.01). The AT-III mRNA levels increased from groups A to C and was positively associated with heparin sensitivity; the factor X mRNA levels changed in the opposite direction; a significant difference was observed between groups A and C (P < 0.05). The factor X plasma level showed the same trend as its mRNA. The AT-III plasma level was significantly lower in group B than in groups A and C (P < 0.05). CONCLUSION: Postoperative blood loss is related to heparin sensitivity in patients undergoing cardiac surgery, and the moderately sensitive patients have the least postoperative bleeding. Individual variation in heparin sensitivity is related to the mRNA and plasma levels of AT-III and factor X. TRIAL REGISTRATION: Registration number ChiCTR-RPC-17012259.

Genomic and Functional Characterization of the Endophytic Bacillus subtilis 7PJ-16 Strain, a Potential Biocontrol Agent of Mulberry Fruit Sclerotiniose.

Bacillus sp. 7PJ-16, an endophytic bacterium isolated from a healthy mulberry stem and previously identified as Bacillus tequilensis 7PJ-16, exhibits strong antifungal activity and has the capacity to promote plant growth. This strain was studied for its effectiveness as a biocontrol agent to reduce mulberry fruit sclerotiniose in the field and as a growth-promoting agent for mulberry in the greenhouse. In field studies, the cell suspension and supernatant of strain 7PJ-16 exhibited biocontrol efficacy and the lowest disease incidence was reduced down to only 0.80%. In greenhouse experiments, the cell suspension (1.0 × 106 and 1.0 × 105 CFU/mL) and the cell-free supernatant (100-fold and 1000-fold dilution) stimulated mulberry seed germination and promoted mulberry seedling growth. In addition, to accurately identify the 7PJ-16 strain and further explore the mechanisms of its antifungal and growth-promoting properties, the complete genome of this strain was sequenced and annotated. The 7PJ-16 genome is comprised of two circular plasmids and a 4,209,045-bp circular chromosome, containing 4492 protein-coding genes and 116 RNA genes. This strain was ultimately designed as Bacillus subtilis based on core genome sequence analyses using a phylogenomic approach. In this genome, we identified a series of gene clusters that function in the synthesis of non-ribosomal peptides (surfactin, fengycin, bacillibactin, and bacilysin) as well as the ribosome-dependent synthesis of tasA and bacteriocins (subtilin, subtilosin A), which are responsible for the biosynthesis of numerous antimicrobial metabolites. Additionally, several genes with function that promote plant growth, such as indole-3-acetic acid biosynthesis, the production of volatile substances, and siderophores synthesis, were also identified. The information described in this study has established a good foundation for understanding the beneficial interactions between endophytes and host plants, and facilitates the further application of B. subtilis 7PJ-16 as an agricultural biofertilizer and biocontrol agent.

Fungi as Architects of the Rimstone Dams in Huanglong, NSD, Sichuan, China.

The Huanglong park area of the Sichuan Province of China is a unique scenic area of the world. It is known for its thousands of aquamarine-colored pools that are formed behind naturally formed rimstone dams of travertine (calcite) along a cold water stream. The travertine, based on its crystalline structural analysis, is of biological origin. This makes sense since the temperature of the waters of Huanglong varies from 5 to 7 °C and thus geochemical crystallization does not occur as it does in other locations around the world possessing thermal pools whose structures are primarily formed through cooling processes. Fungi and bacteria were discovered associated with both leaves associated with the calcite dams as well as in the older parts of well-established dams. Several species of Phytium, a phycomycete and an endophyte, accounted for over 45 % of all of the fungi successfully isolated from the well-established dam samples and at least 85 % in the floating leaf samples. Saprolegnia spp. (Phycomycetes) along with Phoma spp. (Ascomycetes) were noted along with Mortierella sp. as other dam-associated fungi. The fungal hyphae observed on dead leaf material as well as in the calcite dams directly served as nucleation points for the formation of crystalline CaCO3. Eventually, these crystals grow large enough to fuse to make calcite plates which form the main structural feature of all of the travertine dams in this area. Interestingly, each of the individual crystals associated with the dams has an associated hole in its core where a fungal hypha used to reside as observed by scanning electron microscopy. While diatoms were present in the analysis, they too seem to contribute to the structure of the dams but in a minor way. The only bacteria isolated from the older dam of this aquatic environment were Pseudomonas spp. and their role in dam formation is uncertain. Huanglong is a unique and beautiful place, and the water features present in this area can definitely be attributed to those fungal architects that encourage calcite crystal formation.

The critical role of toll-like receptor 4 in bone remodeling of osteoporosis: from inflammation recognition to immunity.

Osteoporosis is a common chronic metabolic bone disorder. Recently, increasing numbers of studies have demonstrated that Toll-like receptor 4 (TLR4, a receptor located on the surface of osteoclasts and osteoblasts) plays a pivotal role in the development of osteoporosis. Herein, we performed a comprehensive review to summarize the findings from the relevant studies within this topic. Clinical data showed that TLR4 polymorphisms and aberrant TLR4 expression have been associated with the clinical significance of osteoporosis. Mechanistically, dysregulation of osteoblasts and osteoclasts induced by abnormal expression of TLR4 is the main molecular mechanism underlying the pathological processes of osteoporosis, which may be associated with the interactions between TLR4 and NF-κB pathway, proinflammatory effects, ncRNAs, and RUNX2. In vivo and in vitro studies demonstrate that many promising substances or agents (i.e., methionine, dioscin, miR-1906 mimic, artesunate, AEG-1 deletion, patchouli alcohol, and Bacteroides vulgatus) have been able to improve bone metabolism (i.e., inhibits bone resorption and promotes bone formation), which may partially attribute to the inhibition of TLR4 expression. The present review highlights the important role of TLR4 in the clinical significance and the pathogenesis of osteoporosis from the aspects of inflammation and immunity. Future therapeutic strategies targeting TLR4 may provide a new insight for osteoporosis treatment.

In vitro and in vivo inhibitory effects of the Sanghuang mushroom extracts against Candida albicans.

Aim: To explore the antifungal potential of Sanghuang mushroom, a traditional Chinese medicine. Materials & methods: The antifungal properties and the potential mechanism of Sanghuang mushroom extracts against Candida albicans were studied in vitro and in vivo. Results: Sanghuang mushroom extracts inhibited the biofilm formation, increased the cell membrane permeability and promoted cell apoptosis of C. albicans in vitro. In a murine model of vulvovaginal candidiasis, Sanghuang mushroom extracts reduced the vaginal fungal load, improved inflammatory cell infiltration and downregulated the expression of TNF-α, IL-1ß and IL-6. Untargeted metabolomic analysis suggested the presence of ten antifungal components in Sanghuang mushroom extracts. Conclusion: Sanghuang mushroom extracts showed promise as antifungal agent against candidiasis, with potential therapeutic implications.

[Box: see text].

Phellintremulins A-C, antinociceptive sesquiterpenoids from the medicinal fungus Phellinus tremulae.

Phellintremulin A (1), a rearranged sesquiterpenoid with an unprecedented bicyclic backbone, and two previously unreported illudane-type sesquiterpenoids, namely phellintremulin B (2) and phellintremulin C (3), together with two known analogues (±)‒4 and (±)‒5, were isolated from cultures of the medicinal fungus Phellinus tremulae. Their structures and absolute configurations were established by means of spectroscopic data and HRESIMS analyses, as well as ECD and NMR calculations. A plausible biogenesis for 1 was discussed. The electrophysiological experiments showed that phellintremulins (A‒C) can inhibit Nav current in DRG neuron cells at 10 µM, with percentage inhibitions of 23.2%, 49.3%, and 31.7%, respectively. The antinociceptive activities of phellintremulins (A‒C) were evaluated via the acetic acid-induced writhing test in mice at a dose of 3 mg/kg. They showed significant antinociceptive effects with percentages of inhibition of 43.8%, 54.4%, and 50.6%, respectively, and phellintremulin B and C expressed more potent analgesic effect than lidocaine.

Prevalence of osteoporosis in patients with nephrolithiasis and vice versa: a cumulative analysis.

Purpose: Nephrolithiasis is thought to be a risk factor for osteoporosis, but data assessing if osteoporosis predisposes to the risk of nephrolithiasis are lacking. The present study aims to investigate whether patients with nephrolithiasis have a prominently higher prevalence of osteoporosis than the controls and vice versa via a cumulative analysis. Methods: Four databases were used to detect the eligible studies. We calculated the relative risk (RR) with a 95% confidence interval (CI) to assess the combined effect. The methodologies for conducting this study followed the PRISMA guidelines and were registered in the PROSPERO (ID: CRD42023395875). Results: Nine case-control or cohort studies with a total of 454,464 participants were finally included. Combined results indicated that there was a significantly higher prevalence of osteoporosis in patients with nephrolithiasis as compared to the general population without nephrolithiasis (overall RR from six studies= 1.204, 95%CI: 1.133 to 1.28, P< 0.001; heterogeneity: I2 = 34.8%, P= 0.162). Conversely, osteoporosis was significantly correlated to an increased risk of nephrolithiasis as compared to the controls without osteoporosis (overall RR from four studies= 1.505, 95%CI: 1.309 to 1.731, P< 0.001; I2 = 89.8%, P< 0.001). Sensitivity analysis on the two categories validated the above findings. No significant publication bias was identified in this study. Conclusions: The present study highlighted a significantly high prevalence of osteoporosis in patients with nephrolithiasis and vice versa. This reciprocal association reminded the clinicians to conduct a regular follow-up assessment when managing patients with nephrolithiasis or osteoporosis, especially for the elderly. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier CRD42023395875.

Network pharmacology-based prediction and validation of the active ingredients and potential mechanisms of the Huangxiong formula for treating ischemic stroke.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangxiong Formula (HXF) is composed of four herbs: Rheum palmatum L., Ligusticum striatum DC., Curcuma aromatica Salisb., and Acorus gramineus Aiton. HXF is clinically used for the treatment of ischemic stroke (IS). However, its molecular mechanism remains unclear. AIM OF THE STUDY: A network pharmacology-based strategy combined with experimental study in vivo and in vitro to were used to investigate the bioactive components, potential targets, and molecular mechanisms of HXF in the treatment of IS. MATERIALS AND METHODS: The components of HXF were detected by ultra-performance liquid chromatography (UPLC). The potential active ingredients of HXF were acquired from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and literature, and corresponding targets were discerned through the Swiss TargetPrediction database. IS-related targets were obtained from Genecards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and DisGeNET. The intersection of ingredient and disease targets was screened, and a herbal-compound-target network was constructed. A protein-protein interaction (PPI) network was created, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Based on these analyses, we established a compound-target-pathway (C-T-P) network. A cerebral ischemia-reperfusion (I/R) animal model was established, and the cerebral protective effect of HXF was assessed. The accuracy of the predicted targets was verified by real-time quantitative polymerase chain reaction (RT-qPCR). Hippocampal neuronal injury cell model induced by oxygen-glucose deprivation and reperfusion (OGD/R) was used to evaluate the protective effect of α-Asarone. Furthermore, molecular docking, drug affinity responsive target stability (DARTS) assay, and cellular thermal shift assay (CETSA) were performed to verify whether α-Asarone can bind to PI3K. RESULTS: A total of 44 active ingredients and 795 gene targets were identified through network pharmacology. Network analysis showed that naringenin, eupatin, kaempferol, and α-Asarone were possible drug candidates. SRC, AKT1, TP53, MAPK3, STAT3, HRAS, CTNNB1, EGFR, VEGFA, PIK3R1 could serve as potential drug targets. KEGG analysis implied that the PI3K/AKT signaling pathway might play an important role in treating IS by HXF. Moreover, HXF significantly reduced neurological impairment, cerebral infarct volume, brain index, and brain histopathological damage in I/R rats. The mRNA expression of the top 10 potential targets was verified in the brain tissue. The C-T-P network and UPLC analysis suggested that α-Asarone might be an important component of HXF and can inhibit oxidative stress and apoptosis in HT22 cells by activating the PI3K/AKT signaling pathway. Molecular docking, DARTS, and CETSA assay analysis confirmed that there were direct interactions between α-Asarone and PI3K. CONCLUSION: HXF had a therapeutic effect in IS with multi-component, multi-target, and multi-approach features. α-Asarone, identified as one of the major active components of HXF, could alleviate oxidative stress and apoptosis by targeting PI3K/AKT pathway.