Effect of Sleeve Gastric Surgery on Body Weight and Hypothalamic-Pituitary Axis Hormone Levels in Patients with Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder in women of reproductive age. It is difficult for patients with PCOS to achieve weight loss with conventional treatment. The aim of this study was to investigate weight loss and changes in hypothalamic-pituitary axis hormone levels in patients with PCOS combined with obesity after sleeve gastrectomy. METHODS: A retrospective analysis of 12 patients without PCOS and 24 patients with PCOS who underwent bariatric surgery at Beijing Luhe hospital from 2020 to 2022 was performed. The study assessed the changes in body weight and hormonal indexes of the hypothalamic-pituitary axis before and six months after the surgery. RESULTS: Patients with PCOS experienced greater weight loss compared to those without the condition. Following surgery, individuals with PCOS showed lower levels of postoperative testosterone, prolactin, and free testosterone indices compared to preoperative levels. Additionally, postoperative LH and FSH levels were higher than preoperative levels. Analysis of thyroid axis hormone levels revealed that FT3 and TSH levels were notably reduced in patients with PCOS postoperatively. Furthermore, growth hormone levels were found to be elevated in patients with PCOS following surgery. CONCLUSION: Bariatric surgery enhances hormone levels in the hypothalamic-pituitary axis in women with PCOS, leading to greater improvements in patients with PCOS compared to those with simple obesity.

The high-bone-mass phenotype of novel transgenic mice with LRP5 A241T mutation.

Gain-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) can cause high-bone-mass (HBM) phenotype, with 19 identified mutations so far. The A242T mutation in LRP5 has been found in 9 families, making it one of the most prevalent mutations. However, the correlation between the A242T mutation and HBM phenotype remains unverified in animal models. This study aimed to investigate the bone properties in a new transgenic mouse model carrying the LRP5 A241T missense mutation, equivalent to A242T in humans. Heterozygous Lrp5A241T mice were generated using CRISPR/Cas9 genome editing. Body weight increased with age from 4 to 16 weeks, higher in males than females, with no difference between Lrp5A241T mice and wild-type control. Micro-CT showed slightly longer femur and notably elevated trabecular bone mass of the femur and fifth lumbar spine with higher bone mineral density, bone volume fraction, and trabecular thickness in Lrp5A241T mice compared to wild-type mice. Additionally, increased cortical bone thickness and volume of the femur shaft and skull were observed in Lrp5A241T mice. Three-point bending tests of the tibia demonstrated enhanced bone strength properties in Lrp5A241T mice. Histomorphometry confirmed that the A241T mutation increased bone formation without affecting osteoblast number and reduced resorption activities in vivo. In vitro experiments indicated that the LRP5 A241T mutation enhanced osteogenic capacity of osteoblasts with upregulation of the Wnt signaling pathway, with no significant impact on the resorptive activity of osteoclasts. In summary, mice carrying the LRP5 A241T mutation displayed high bone mass and quality due to enhanced bone formation and reduced bone resorption in vivo, potentially mediated by the augmented osteogenic potential of osteoblasts. Continued investigation into the regulatory mechanisms of its bone metabolism and homeostasis may contribute to the advancement of novel therapeutic strategies for bone disorders.

IL-6 Inhibitor Tocilizumab Reduces Bone Resorption Around Implants with Bacterial Infection During Osseointegration: A Pilot Study in Rabbits.

PURPOSE: To evaluate the effect of interleukin-6 (IL-6) inhibitor (tocilizumab) on bacterial infection-associated bone resorption around implants during osseointegration in rabbits. MATERIALS AND METHODS: At total of 24 male, 9-monthold New Zealand white rabbits were included, and their two mandibular anterior teeth were extracted. Three months after extraction, 24 one-piece Dentium implants (Ø 2.5 mm, intraosseous length of 12 mm) were inserted in the anterior mandible, and the rabbits were divided into four groups (n = 6 per group). Different treatment methods were used in each group: blank control group (BC); only silk ligation (negative control [NC]); silk ligation and injection with minocycline hydrochloride ointment (positive control [PC]); and silk ligation and injection with tocilizumab at 8 mg/kg via the auricle vein (experimental [EP]). Eight weeks later, the animals were sacrificed, and samples were collected and then analyzed using microcomputed tomography (microCT) scanning, immunohistochemical analysis, and histologic analysis. RESULTS: From the microCT measurement, the ratio of the bone volume to the total volume (BV/TV) in the EP group was 67.00% ± 2.72%, which was higher than that in the other three groups (58.85% ± 2.43% in the BC group, 55.72% ± 2.48% in the PC group, and 36.52% ± 3.02% in the NC group). From immunohistochemical analysis, the expression of IL-6 was found to be higher in the NC group than in the BC, PC, and EP groups, but there was no statistical difference between these three groups. Furthermore, the RANKL (receptor activator of nuclear factor-κB ligand) expression was the lowest in the EP group, followed by the BC group, the PC group, and the NC group, which had the highest expression; there was no difference between the NC and PC groups. Upon histologic analysis, significant new bone was found on the implant surfaces in the EP group, sparse and less new bone could be seen in the BC and PC groups, and the most serious bone resorption occurred in the NC group. CONCLUSIONS: Tocilizumab, an inhibitor of IL-6, has a certain effect in preventing bone loss around implants caused by bacterial infection during the osseointegration period.

G272V and P301L mutations induce isoform specific tau mislocalization to dendritic spines and synaptic dysfunctions in cellular models of 3R and 4R tau frontotemporal dementia.

Tau pathologies are detected in the brains of some of the most common neurodegenerative diseases including Alzheimer's disease (AD), Lewy body dementia (LBD), chronic traumatic encephalopathy (CTE), and frontotemporal dementia (FTD). Tau proteins are expressed in six isoforms with either three or four microtubule-binding repeats (3R tau or 4R tau) due to alternative RNA splicing. AD, LBD, and CTE brains contain pathological deposits of both 3R and 4R tau. FTD patients can exhibit either 4R tau pathologies in most cases, or 3R tau pathologies less commonly in Pick's disease, which is a subfamily of FTD. Here, we report the isoform-specific roles of tau in FTD. The P301L mutation, linked to familial 4R tau FTD, induces mislocalization of 4R tau to dendritic spines in primary hippocampal cultures that were prepared from neonatal rat pups of both sexes. Contrastingly, the G272V mutation, linked to familial Pick's disease, induces phosphorylation-dependent mislocalization of 3R tau but not 4R tau proteins to dendritic spines. The overexpression of G272V 3R tau but not 4R tau proteins leads to the reduction of dendritic spine density and suppression of miniature excitatory synaptic currents (mEPSCs) in 5-week-old primary rat hippocampal cultures. The decrease in mEPSC amplitude caused by G272V 3R tau is dynamin dependent whereas that caused by P301L 4R tau is dynamin independent, indicating that the two tau isoforms activate different signaling pathways responsible for excitatory synaptic dysfunction. Our 3R and 4R tau studies here will shed new light on diverse mechanisms underlying FTD, AD, LBD, and CTE.Significance statement Frontotemporal dementia is the third most common form of dementia caused by neurodegeneration with diverse clinical presentations. Here, we report distinct cellular mechanisms that may explain some of the similarities and differences between diverse forms of frontotemporal dementia. Tau proteins are composed of six isoforms. We found that although all isoforms can cause neural deficits, each isoform may impair the structures and functions of neurons with different temporal dynamics or through different mechanisms. The mechanistic studies of isoform-specific tau-mediated synaptic impairments reported here will add valuable information to the current molecular and cellular framework, by which diverse tau isoforms cause brain deficits in frontotemporal dementia and other neurodegenerative diseases including Alzheimer's diseases, Lewy body dementia, and chronic traumatic encephalopathy.

Metastatic clear cell sarcoma of the pancreas: From diagnosis to treatment.

This article presents a comprehensive case report on an uncommon instance of metastatic clear cell sarcoma (CCS) originating from the pancreas. The high mortality rate of pancreatic carcinoma underscores the importance of precise diagnosis and early detection. The authors report a novel case of CCS with pancreatic metastasis, detailing successful surgical intervention through distal pancreatectomy and splenectomy, resulting in favourable outcomes. This study highlights the standard role of surgery in treating advanced CCS and emphasizes preoperative imaging and thorough patient history assessment. This article also underscores the necessity for long-term surveillance due to the potential for recurrence or metastasis. Despite the favourable recovery postsurgery, the absence of subsequent follow-up evaluation prompts consideration of the need for extended monitoring. This article raises questions about the nature of the pancreatic lesion and suggests the possibility of a primary lesion. Further evidence is crucial to establish the correlation between the features related to the development of the patient's primary and metastatic tumours. In conclusion, this study offers valuable insights into metastatic CCS of the pancreas, highlighting the importance of regular postoperative follow-up for improved outcomes through early detection and intervention.

Black rice diet alleviates colorectal cancer development through modulating tryptophan metabolism and activating AHR pathway.

Consumption of dietary fiber and anthocyanin has been linked to a lower incidence of colorectal cancer (CRC). This study scrutinizes the potential antitumorigenic attributes of a black rice diet (BRD), abundantly rich in dietary fiber and anthocyanin. Our results demonstrate notable antitumorigenic effects in mice on BRD, indicated by a reduction in both the size and number of intestinal tumors and a consequent extension in life span, compared to control diet-fed counterparts. Furthermore, fecal transplants from BRD-fed mice to germ-free mice led to a decrease in colonic cell proliferation, coupled with maintained integrity of the intestinal barrier. The BRD was associated with significant shifts in gut microbiota composition, specifically an augmentation in probiotic strains Bacteroides uniformis and Lactobacillus. Noteworthy changes in gut metabolites were also documented, including the upregulation of indole-3-lactic acid and indole. These metabolites have been identified to stimulate the intestinal aryl hydrocarbon receptor pathway, inhibiting CRC cell proliferation and colorectal tumorigenesis. In summary, these findings propose that a BRD may modulate the progression of intestinal tumors by fostering protective gut microbiota and metabolite profiles. The study accentuates the potential health advantages of whole-grain foods, emphasizing the potential utility of black rice in promoting health.

Genome-wide identification and expression analysis of the SPL transcription factor family and its response to abiotic stress in Pisum sativum L.

Squamous promoter binding protein-like (SPL) genes encode plant-specific transcription factors (TFs) that play essential roles in modulating plant growth, development, and stress response. Pea (Pisum sativum L.) is a coarse grain crop of great importance in food production, biodiversity conservation and molecular genetic research, providing genetic information and nutritional resources for improving agricultural production and promoting human health. However, only limited researches on the structure and functions of SPL genes exist in pea (PsSPLs). In this study, we identified 22 PsSPLs and conducted a genome-wide analysis of their physical characteristics, chromosome distribution, gene structure, phylogenetic evolution and gene expression patterns. As a result, the PsSPLs were unevenly distributed on the seven chromosomes of pea and harbored the SBP domain, which is composed of approximately 76 amino acid residues. The phylogenetic analysis revealed that the PsSPLs clustered into eight subfamilies and showed high homology with SPL genes in soybean. Further analysis showed the presence of segmental duplications in the PsSPLs. The expression patterns of 22 PsSPLs at different tissues, developmental stages and under various stimulus conditions were evaluated by qRT-PCR method. It was found that the expression patterns of PsSPLs from the same subfamily were similar in different tissues, the transcripts of most PsSPLs reached the maximum peak value at 14 days after anthesis in the pod. Abiotic stresses can cause significantly up-regulated PsSPL19 expression with spatiotemporal specificity, in addition, four plant hormones can cause the up-regulated expression of most PsSPLs including PsSPL19 in a time-dependent manner. Therefore, PsSPL19 could be a key candidate gene for signal transduction during pea growth and development, pod formation, abiotic stress and plant hormone response. Our findings should provide insights for the elucidating of development regulation mechanism and breeding for resistance to abiotic stress pea.

Inhibition of the ATR-DNAPKcs-RB axis drives G1/S-phase transition and sensitizes triple-negative breast cancer (TNBC) to DNA holliday junctions.

Targeting the DNA damage response (DDR) is a promising strategy in oncotherapy, as most tumor cells are sensitive to excess damage due to their repair defects. Ataxia telangiectasia mutated and RAD3-related protein (ATR) is a damage response signal transduction sensor, and its therapeutic potential in tumor cells needs to be precisely investigated. Herein, we identified a new axis that could be targeted by ATR inhibitors to decrease the DNA-dependent protein kinase catalytic subunit (DNAPKcs), downregulate the expression of the retinoblastoma (RB), and drive G1/S-phase transition. Four-way DNA Holliday junctions (FJs) assembled in this process could trigger S-phase arrest and induce lethal chromosome damage in RB-positive triple-negative breast cancer (TNBC) cells. Furthermore, these unrepaired junctions also exerted toxic effects to RB-deficient TNBC cells when the homologous recombination repair (HRR) was inhibited. This study proposes a precise strategy for treating TNBC by targeting the DDR and extends our understanding of ATR and HJ in tumor treatment.

Extracellular matrix stiffness and tumor-associated macrophage polarization: new fields affecting immune exclusion.

In the malignant progression of tumors, there is deposition and cross-linking of collagen, as well as an increase in hyaluronic acid content, which can lead to an increase in extracellular matrix stiffness. Recent research evidence have shown that the extracellular matrix plays an important role in angiogenesis, cell proliferation, migration, immunosuppression, apoptosis, metabolism, and resistance to chemotherapeutic by the alterations toward both secretion and degradation. The clinical importance of tumor-associated macrophage is increasingly recognized, and macrophage polarization plays a central role in a series of tumor immune processes through internal signal cascade, thus regulating tumor progression. Immunotherapy has gradually become a reliable potential treatment strategy for conventional chemotherapy resistance and advanced cancer patients, but the presence of immune exclusion has become a major obstacle to treatment effectiveness, and the reasons for their resistance to these approaches remain uncertain. Currently, there is a lack of exact mechanism on the regulation of extracellular matrix stiffness and tumor-associated macrophage polarization on immune exclusion. An in-depth understanding of the relationship between extracellular matrix stiffness, tumor-associated macrophage polarization, and immune exclusion will help reveal new therapeutic targets and guide the development of clinical treatment methods for advanced cancer patients. This review summarized the different pathways and potential molecular mechanisms of extracellular matrix stiffness and tumor-associated macrophage polarization involved in immune exclusion and provided available strategies to address immune exclusion.

Application of Carbon Nanoparticles in Transoral Endoscopic Thyroidectomy Vestibular Approach for Unilateral Papillary Thyroid Cancer.

BACKGROUND: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is newly applied technology. Carbon nanoparticles (CNs) are novel lymph node tracers that have been widely used in China to help remove central lymph nodes (CLNs) and protect the parathyroid glands (PGs) in open thyroid cancer surgery. This study is to evaluate the effectiveness and safety of CNs in TOETVA. MATERIALS AND METHODS: A total of 158 patients who underwent TOETVA with unilateral papillary thyroid carcinoma were enrolled in this study from March 2019 to February 2022. The participants were divided into a CNs group (n=88) and a control group (n=70), based on whether they received a intraoperative injection of CNs or not. Meanwhile, the CNs group were additionally divided into 2 subgroups, leakage subgroup (n=26) and standard subgroup (n=62). The 2 groups and subgroups were compared in terms of patient characteristics, perioperative clinical results, and postoperative outcomes. RESULTS: All common metrics had no significant differences were found between the CNs group and the control group ( P >0.05). The standard subgroup of CNs group had advantage over the control group on PGs identification (59/62 vs. 59/70 for superior PG, 56/62 vs. 52/70 for inferior PG, P <0.05). Moreover, the standard subgroup harvested more CLNs than the control group (8.97±2.96 vs. 7.47±2.93, P <0.05). More operation time was spent on the leakage subgroup of CNs group than the control group (160.00±17.61 vs. 140.00±13.32, P <0.05). Meanwhile, the leakage subgroup had disadvantage on intraoperative hemorrhage (26.15±10.80 vs. 21.21±7.09, P <0.05) and hospital durations (4.96±0.72 vs. 4.57±0.69, P <0.05). Furthermore, the leakage group identified fewer inferior PG than the control group (7/26 vs. 52/70, P <0.05). Contrary to the standard subgroup, the CLNs of the leakage subgroup was also unsatisfactory compared with the control group (4.96±1.84 vs. 7.47±2.93, P <0.05). CONCLUSIONS: The application of CNs suspension tracing technology has a definite effect in TOETVA. It can improve the thoroughness of lymph node dissection in the central region and enhance recognition of the PG. However, refined extracapsular anatomy is indispensable to prevent CN leakage. Leaked CNs will also be counterproductive to the operation.

The emerging and legacy persistent organic contaminants in corals of the South China Sea.

Seawater warming, ocean acidification and chemical pollution are the main threats to coral growth and even survival. The legacy persistent organic contaminants (POCs), such as polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), and the emerging contaminants, including polybrominated diphenyl ethers (PBDEs), dechlorane plus (DPs) and novel brominated flame retardants (NBFRs) were studied in corals from Luhuitou fringing reef in Sanya Bay and Yongle atoll in Xisha Islands, the South China Sea (SCS). Total average concentrations of ∑16PAHs, ∑23OCPs, ∑34PCBs, ∑8PBDEs, ∑2DPs and ∑5NBFRs in 20 coral species (43 samples) from the SCS were 40.7 ± 34.6, 5.20 ± 5.10, 0.197 ± 0.159, 3.30 ± 3.70, 0.041 ± 0.042 and 36.4 ± 112 ng g-1 dw, respectively. PAHs and NBFRs were the most abundant compounds and they are likely to be dangerous pollutants for future coral growth. Compared to those found in other coral reef regions, these pollutants concentrations in corals were at low to median levels. Except for PBDEs, POCs in massive Porites were significantly higher than those in branch Acropora and Pocillopora (p < 0.01), as large, closely packed corals may be beneficial for retaining more pollutant. The current study contributes valuable data on POCs, particularly for halogenated flame retardants (HFRs, including PBDEs, DPs and NBFRs), in corals from the SCS, and will improve our knowledge of the occurrence and fate of these pollutants in coral reef ecosystems.

Identification of the new molecular subtypes related to inflammation in breast cancer.

Breast cancer is a prevalent ailment among women, and the inflammatory response plays a crucial role in the management and prediction of breast cancer (BRCA). However, the new subtypes based on inflammation in BRCA research are still undefined. The databases including The Cancer Genome Atlas and gene expression omnibus were utilized to gather clinical data and somatic mutation information for approximately 1069 BRCA patients. Through Consensus Clustering, novel subtypes linked to inflammation were identified. A comparative analysis was conducted on the prognosis, and immune cell infiltration, and somatic mutation of the new subtypes. Additionally, an investigation into drug therapy and immunotherapy was conducted to distinguish high-risk individuals from low-risk ones. The findings of this investigation proposed the categorization of BRCA into innovative subtypes predicated on the inflammatory response and 6 key genes were a meaningful approach. Specifically, the low-, medium-, and high-inflammation subtypes exhibited varying degrees of association with clinicopathological features, tumor microenvironment, and prognosis. Notably, the high-inflammation subtype was characterized by a strong correlation with immunosuppressive microenvironments and a higher frequency of somatic mutations, which was an indication of poorer health. This study revealed that a brand-new classification could throw new light on the effective prognosis. The integration of multiple key genes was a new characterization that could promote more immunotherapy strategies and contribute to predicting the efficacy of the chemotherapeutic drugs.

Suspected coexistence of perianal necrotizing sweet syndrome in chronic myelomonocytic leukemia: A case report.

BACKGROUND: Chronic myelomonocytic leukemia (CMML) complicated with Sweet syndrome (SS) is a rare hematological neoplasm. However, cases of concomitant development of perianal necrotizing SS (NSS) have not been reported. CASE SUMMARY: We report a case of a 49-year-old male patient who underwent sequential procedures for hemorrhoids and perianal abscess. He developed postoperative incision infection and was referred to the department where the authors work. Initially, perianal necrotizing fasciitis secondary to incision infection after perianal abscess surgery was suspected. Despite receiving antibiotic therapy and undergoing surgical debridement, deeper necrotic areas formed in the patient's perianal wounds, accompanied by persistent high fever. Blood and fungal cultures yielded negative results. The final diagnosis was corrected to be CMML with suspected concomitant perianal NSS. CONCLUSION: CMML with perianal NSS is a rare condition, often misdiagnosed as perianal abscess or perianal necrotizing fasciitis. Conventional antibiotic therapy and surgical debridement are ineffective in managing this condition.

Dynamics of α-glucan from Agrocybe cylindracea water extract at different developmental stages and its structure characteristics.

Polysaccharides are the important bioactive macromolecules in Agrocybe cylindracea, but their changes are as yet elusive during developmental process. This study investigated the dynamic changes of polysaccharides from A. cylindracea fruiting body water extract at four developmental stages and its structure characteristics. Results revealed that the polysaccharides from A. cylindracea water extract significantly increased at the pileus expansion stage and the increased fraction could be α-glucan. The further purification and identification indicated that this α-glucan was a glycogen. It had typical morphology of ß particles with a molecular weight of 1375 kDa. Its backbone comprised α-D-(1 â†’ 4)-Glcp and α-D-(1 â†’ 4,6)-Glcp residues at a ratio of 5:1, terminated by α-D-Glcp residue. Rheological behavior suggested that it was a Newtonian fluid at the concentration of 1 %. In addition, despite both the glycogen and natural starch were composed of D-glucose, they exhibited the entirely distinct Maltese cross characteristic and unique crystalline structure. This study is the first to demonstrate the presence of abundant glycogen in the pileus expansion stage of A. cylindracea, which provides new insights on the change patterns of fungal polysaccharides.

The Longitudinal Relationships among Casual Sex and Psychological Well-Being in Chinese College Student.

This study integrates the important psychological well-being indicators (i.e., life satisfaction, psychological distress, and self-esteem) into a model framework. We used a cross-lagged panel design (CLPD) to examine the bidirectional relationship between casual sex and psychological well-being among Chinese college students. Chinese college students (N = 833) completed self-report measures (i.e., hookup behavior, life satisfaction, psychological distress, and self-esteem) at six-month intervals. The results show that the ratio of college students who reported engaging in at least one hookup experience in the past year or half a year was lower than that of Western college students. We find that college students with hookup behavior had poorer psychological well-being in later six months than those who did not engage in hookup behavior. However, previous psychological well-being did not predict subsequent hookup behavior. We discuss these findings in terms of China's unique sexual culture to provide useful information for preventing and interfering with risky sexual behaviors and their negative consequences among Chinese college students. Specifically, this study could provide students with a more in-depth understanding of associated risks, assisting those engaged in or intending to engage in hookups to evaluate the advantages and drawbacks of such behavior. Furthermore, it underscores the importance of implementing targeted educational programs in China that address the psychological consequences of casual sex.

HMGB2 Release Promotes Pulmonary Hypertension and Predicts Severity and Mortality of Patients With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a progressive and life-threatening disease characterized by pulmonary vascular remodeling, which involves aberrant proliferation and apoptosis resistance of the pulmonary arterial smooth muscle cells (PASMCs), resembling the hallmark characteristics of cancer. In cancer, the HMGB2 (high-mobility group box 2) protein promotes the pro-proliferative/antiapoptotic phenotype. However, the function of HMGB2 in PH remains uninvestigated. METHODS: Smooth muscle cell (SMC)-specific HMGB2 knockout or HMGB2-OE (HMGB2 overexpression) mice and HMGB2 silenced rats were used to establish hypoxia+Su5416 (HySu)-induced PH mouse and monocrotaline-induced PH rat models, respectively. The effects of HMGB2 and its underlying mechanisms were subsequently elucidated using RNA-sequencing and cellular and molecular biology analyses. Serum HMGB2 levels were measured in the controls and patients with pulmonary arterial (PA) hypertension. RESULTS: HMGB2 expression was markedly increased in the PAs of patients with PA hypertension and PH rodent models and was predominantly localized in PASMCs. SMC-specific HMGB2 deficiency or silencing attenuated PH development and pulmonary vascular remodeling in hypoxia+Su5416-induced mice and monocrotaline-treated rats. SMC-specific HMGB2 overexpression aggravated hypoxia+Su5416-induced PH. HMGB2 knockdown inhibited PASMC proliferation in vitro in response to PDGF-BB (platelet-derived growth factor-BB). In contrast, HMGB2 protein stimulation caused the hyperproliferation of PASMCs. In addition, HMGB2 promoted PASMC proliferation and the development of PH by RAGE (receptor for advanced glycation end products)/FAK (focal adhesion kinase)-mediated Hippo/YAP (yes-associated protein) signaling suppression. Serum HMGB2 levels were significantly increased in patients with PA hypertension, and they correlated with disease severity, predicting worse survival. CONCLUSIONS: Our findings indicate that targeting HMGB2 might be a novel therapeutic strategy for treating PH. Serum HMGB2 levels could serve as a novel biomarker for diagnosing PA hypertension and determining its prognosis.

Resourceful application and mechanism of oyster shell-microalgae synergistic system：Sustainable treatment of harsh low carbon nitrogen ratio actual wastewater.

Microalgal technology holds great promise for both low C/N wastewater treatment and resource recovery simultaneously. Nevertheless, the advancement of microalgal technology is hindered by its reduced nitrogen removal efficiency in low C/N ratio wastewater. In this work, microalgae and waste oyster shells were combined to achieve a total inorganic nitrogen removal efficiency of 93.85% at a rate of 2.05 mg L-1 h-1 in low C/N wastewater. Notably, over four cycles of oyster shell reuse, the reactor achieved an average 85% ammonia nitrogen removal extent, with a wastewater treatment cost of only $0.092/ton. Moreover, microbial community analysis during the reuse of oyster shells revealed the critical importance of timely replacement in inhibiting the growth of non-functional bacteria (Poterioochromonas_malhamensi). The work demonstrated that the oyster shell - microalgae system provides a time- and cost-saving, environmental approach for the resourceful treatment of harsh low C/N wastewater.

Integrative Dissection of Lignin Composition in Tartary Buckwheat Seed Hulls for Enhanced Dehulling Efficiency.

The rigid hull encasing Tartary buckwheat seeds necessitates a laborious dehulling process before flour milling, resulting in considerable nutrient loss. Investigation of lignin composition is pivotal in understanding the structural properties of tartary buckwheat seeds hulls, as lignin is key determinant of rigidity in plant cell walls, thus directly impacting the dehulling process. Here, the lignin composition of seed hulls from 274 Tartary buckwheat accessions is analyzed, unveiling a unique lignin chemotype primarily consisting of G lignin, a common feature in gymnosperms. Furthermore, the hardness of the seed hull showed a strong negative correlation with the S lignin content. Genome-wide detection of selective sweeps uncovered that genes governing the biosynthesis of S lignin, specifically two caffeic acid O-methyltransferases (COMTs) and one ferulate 5-hydroxylases, are selected during domestication. This likely contributed to the increased S lignin content and decreased hardness of seed hulls from more domesticated varieties. Genome-wide association studies identified robust associations between FtCOMT1 and the accumulation of S lignin in seed hull. Transgenic Arabidopsis comt1 plants expressing FtCOMT1 successfully reinstated S lignin content, confirming its conserved function across plant species. These findings provide valuable metabolic and genetic insights for the potential redesign of Tartary buckwheat seed hulls.

Not exclusively the activity, but the sweet spot: a dehydrogenase point mutation synergistically boosts activity, substrate tolerance, thermal stability and yield.

Catalytic activity is undoubtedly a key focus in enzyme engineering. The complicated reaction conditions hinder some enzymes from industrialization even though they have relatively promising activity. This has occurred to some dehydrogenases. Hydroxysteroid dehydrogenases (HSDHs) specifically catalyze the conversion between hydroxyl and keto groups, and hold immense potential in the synthesis of steroid medicines. We underscored the importance of 7α-HSDH activity, and analyzed the overall robustness and underlying mechanisms. Employing a high-throughput screening approach, we comprehensively assessed a mutation library, and obtained a mutant with enhanced enzymatic activity and overall stability/tolerance. The superior mutant (I201M) was identified to harbor improved thermal stability, substrate susceptibility, cofactor affinity, as well as the yield. This mutant displayed a 1.88-fold increase in enzymatic activity, a 1.37-fold improvement in substrate tolerance, and a 1.45-fold increase in thermal stability when compared with the wild type (WT) enzyme. The I201M mutant showed a 2.25-fold increase in the kcat/KM ratio (indicative of a stronger binding affinity for the cofactor). This mutant did not exhibit the highest enzyme activity compared with all the tested mutants, but these improved characteristics contributed synergistically to the highest yield. When a substrate at 100 mM was present, the 24 h yield by I201M reached 89.7%, significantly higher than the 61.2% yield elicited by the WT enzyme. This is the first report revealing enhancement of the catalytic efficiency, cofactor affinity, substrate tolerance, and thermal stability of NAD(H)-dependent 7α-HSDH through a single-point mutation. The mutated enzyme reached the highest enzymatic activity of 7α-HSDH ever reported. High enzymatic activity is undoubtedly crucial for enabling the industrialization of an enzyme. Our findings demonstrated that, when compared with other mutants boasting even higher enzymatic activity, mutants with excellent overall robustness were superior for industrial applications. This principle was exemplified by highly active enzymes such as 7α-HSDH.

Bioactive solanidane steroidal alkaloids from Solanum lyratum.

Six previously unreported solanidane steroidal alkaloids, namely lyrasolanosides A-F, were isolated from Solanum lyratum. In addition, five known steroidal alkaloids were also identified. The structures of these compounds were determined through the use of NMR, HRESIMS,UV, IR and ECD analysis. To assess their bioactivities, the cytotoxic effects of the six previously unreported compounds were evaluated on A549 cells. The results revealed that lyrasolanoside B (2) exhibited the highest potency among them. Lyrasolanoside B (2) exhibited significant inhibition of cell migration, invasion, and adhesion dramatically. Mechanistically, it was found to suppress the activity of JAK2/STAT3 signaling pathway by downregulating the expression of phosphorylated JAK2/STAT3 in an exosome-dependent manner. In addition, lyrasolanoside B (2) was found to significantly upregulate the expression of E-cadherin and downregulate the expression of N-cadherin and vimentin. These findings indicate that lyrasolanoside B (2) inhibits the metastasis of A549 cells by suppressing exosome-mediated EMT. These findings suggest that lyrasolanoside B (2) may inhibit the metastasis of lung cancer by regulating A549-derived exosomes.