Changes in hemicellulose metabolism in banana peel during fruit development and ripening.

Hemicellulose is key in determining the fate of plant cell wall in almost all growth and developmental stages. Nevertheless, there is limited knowledge regarding its involvement in the development and ripening of banana fruit. This study investigated changes in the temporal-spatial distribution of various hemicellulose components, hemicellulose content, activities of the main hydrolysis enzymes, and transcription level of the main hemicellulose-related gene families in banana peels. Both hemicellulose and xylan contents were positively correlated to the fruit firmness observed in our previous study. On the contrary, the xylanase activity was negatively correlated to xylan content and the fruit firmness. The vascular bundle cells, phloem, and cortex of bananas are abundant in xyloglucan, xylan, and mannan contents. Interestingly, the changes in the signal intensity of the CCRC-M104 antibody recognizing non-XXXG type xyloglucan are positively correlated to hemicellulose content. According to RNA-Seq analysis, xyloglucan and xylan-related genes were highly active in the early stages of growth, and the expression of MaMANs and MaXYNs increased as the fruit ripened. The abundance of plant hormonal and growth-responsive cis-acting elements was detected in the 2 kb upstream region of hemicellulose-related gene families. Interaction between hemicellulose and cell wall-specific proteins and MaKCBP1/2, MaCKG1, and MaHKL1 was found. The findings shed light on cell wall hemicellulose's role in banana fruit development and ripening, which could improve nutrition, flavor, and reduce postharvest fruit losses.

Accuracy of ultrasound-guided iliopsoas tendon injection after total hip arthroplasty: a retrospective observational study.

PURPOSE: To describe and characterize the accuracy and benefit of a technique for performing ultrasound-guided needle placement for iliopsoas peritendon or bursa injections as an alternative method to fluoroscopic guidance. MATERIALS AND METHODS: Patients with a history of total hip arthroplasty who were referred by their orthopedic surgeon for iliopsoas peritendon or bursa corticosteroid injection for iliopsoas impingement syndrome between June 2017 and December 2019 were eligible for inclusion. Of these patients, 19 received a total of 26 ultrasound-guided needle placement followed by confirmatory fluoroscopic guidance prior to injection. Pre-injection and post-injection VAS scores were collected to monitor pain. Additionally, the patients were followed for 6 months via chart review after their injection to assess for complications, need for repeat injections, and progression to surgical intervention. The accuracy of a longitudinal in-plane distal to proximal approach to ultrasound guided needle placement was then evaluated. RESULTS: Ultrasound guided needle placement using a longitudinal in-plane distal to proximal approach demonstrated spread of contrast material in the intended anatomic location with fluoroscopic confirmation in patients who underwent iliopsoas peritendon or bursa injection post total hip arthroplasty. CONCLUSION: Ultrasound guided needle placement using a longitudinal in-plane distal to proximal approach can be an effective alternative technique for diagnostic or therapeutic iliopsoas peritendon injection in patients with total hip arthroplasty.

Overlapping syndrome of anti-MOG antibody-associated disease and anti-mGluR5 encephalitis manifested as optic neuritis: A case report.

RATIONALE: Anti-Myelin oligodendrocyte glycoprotein (MOG) and anti-metabotropic glutamate receptor 5 (mGluR5) double antibody positive encephalitis characterized by optic neuritis is extremely rare. We present a case of overlapping syndrome of MOG-IgG-associated disease and anti-mGluR5 encephalitis manifested as optic neuritis. PATIENT CONCERNS: A 60-year-old Chinses woman presented to the hospital with progressive vision loss and headache for 1 week. The cerebrospinal fluid examination was within the normal range. Visual evoked potentials study disclosed prolonged latency of P100 bilaterally. Fundus examination revealed indistinct boundaries of both optic discs. Her brain magnetic resonance imaging showed patchy hyperintensity in the posterior horn of the left ventricle and the left optic nerve. Her serum was positive for anti-MOG and anti-mGluR5 antibodies. DIAGNOSIS: The patient was diagnosed with overlapping syndrome of anti-MOG antibody-associated disease and anti-mGluR5 encephalitis mainly based on the clinical symptoms and further test of the antibody in serum. INTERVENTIONS AND OUTCOMES: She was subsequently subjected to empirical treatment with intravenous methylprednisolone. After discharge, she was given a tapering dose of oral prednisone, alongside mycophenolate mofetil. On outpatient follow-up, her symptoms showed no relapse after 1 month, and her condition remained stable. LESSONS: Early recognition of autoimmune encephalitis is crucial. The detection of cerebrospinal fluid and serum of autoimmune encephalitis and demyelinating diseases of the CNS, including MOG-IgG and mGluR5-IgG, should be strengthened in order to make a precise diagnosis and develop a comprehensive treatment plan in a timely manner.

Advanced electrochemical membrane technologies for near-complete resource recovery and zero-discharge of urine: Performance optimization and evaluation.

The depletion of nutrient sources in fertilizers demands a paradigm shift in the treatment of nutrient-rich wastewater, such as urine, to enable efficient resource recovery and high-value conversion. This study presented an integrated bipolar membrane electrodialysis (BMED) and hollow fiber membrane (HFM) system for near-complete resource recovery and zero-discharge from urine treatment. Computational simulations and experimental validations demonstrated that a higher voltage (20 V) significantly enhanced energy utilization, while an optimal flow rate of 0.4 L/min effectively mitigated the negative effects of concentration polarization and electro-osmosis on system performance. Within 40 min, the process separated 90.13% of the salts in urine, with an energy consumption of only 8.45 kWh/kgbase. Utilizing a multi-chamber structure for selective separation, the system achieved recovery efficiencies of 89% for nitrogen, 96% for phosphorus, and 95% for potassium from fresh urine, converting them into high-value products such as 85 mM acid, 69.5 mM base, and liquid fertilizer. According to techno-economic analysis, the cost of treating urine using this system at the lab-scale was $6.29/kg of products (including acid, base, and (NH4)2SO4), which was significantly lower than the $20.44/kg cost for the precipitation method to produce struvite. Excluding fixed costs, a net profit of $18.24/m3 was achieved through the recovery of valuable products from urine using this system. The pilot-scale assessment showed that the net benefit amounts to $19.90/m3 of urine, demonstrating significant economic feasibility. This study presents an effective approach for the near-complete resource recovery and zero-discharge treatment of urine, offering a practical solution for sustainable nutrient recycling and wastewater management.

Combined First-Principles and Experimental Investigation into the Reactivity of Codeposited Chromium-Carbon under Pressure.

High-pressure synthesis in the diamond anvil cell suffers from the lack of a general approach for the control of precursor stoichiometry and homogeneity. Here, we present results from a new method we have developed that uses magnetron cosputtering to prepare stoichiometrically precise and atomically mixed amorphous films of Cr:C. Laser-heated diamond anvil cell experiments carried out on a flake of this sample at pressures between 13.5 and 24.3 GPa lead to the observation of Cr3C (Pnma) over the entire pressure range-in good agreement with our in-house theoretical predictions-but also reveal two other metastable phases that were not expected: a novel monoclinic chromium carbide phase and the NaCl-type CrC (Fm3̅m) phase. The unexpected stability of CrC is investigated by using first-principles methods, revealing a large stabilizing effect tied to substoichiometry at the carbon site. These results offer an important case study into the current limitations of crystal structure prediction methods with regard to phase complexity and bolster the growing need for advanced theoretical approaches that can more completely survey experimentally unexplored phase space.

Alternative molecular mechanisms for force transmission at adherens junctions via ß-catenin-vinculin interaction.

Force transmission through adherens junctions (AJs) is crucial for multicellular organization, wound healing and tissue regeneration. Recent studies shed light on the molecular mechanisms of mechanotransduction at the AJs. However, the canonical model fails to explain force transmission when essential proteins of the mechanotransduction module are mutated or missing. Here, we demonstrate that, in absence of α-catenin, ß-catenin can directly and functionally interact with vinculin in its open conformation, bearing physiological forces. Furthermore, we found that ß-catenin can prevent vinculin autoinhibition in the presence of α-catenin by occupying vinculin´s head-tail interaction site, thus preserving force transmission capability. Taken together, our findings suggest a multi-step force transmission process at AJs, where α-catenin and ß-catenin can alternatively and cooperatively interact with vinculin. This can explain the graded responses needed to maintain tissue mechanical homeostasis and, importantly, unveils a force-bearing mechanism involving ß-catenin and extended vinculin that can potentially explain the underlying process enabling collective invasion of metastatic cells lacking α-catenin.

Chromosome-level genome assembly and annotation of xerophyte secretohalophyte Reaumuria soongarica.

Reaumuria soongarica is a xerophytic shrub belonging to the Tamaricaceae family. The species is widely distributed in the deserts of Central Asia and is characterized by its remarkable adaptability to saline and barren desert environments. Using PacBio long-read sequencing and Hi-C technologies, we assembled a chromosome-level genome of R. soongarica. The genome assembly has a size of 1.28 Gb with a scaffold N50 of 116.15 Mb, and approximately 1.25 Gb sequences were anchored in 11 pseudo-chromosomes. A completeness assessment of the assembled genome revealed a BUSCO score of 97.5% and an LTR Assembly Index of 12.37. R. soongarica genome had approximately 60.07% repeat sequences. In total, 21,791 protein-coding genes were predicted, of which 95.64% were functionally annotated. This high-quality genome will serve as a foundation for studying the genomic evolution and adaptive mechanisms to arid-saline environments in R. soongarica, facilitating the exploration and utilization of its unique genetic resources.

De novo design of a nanoregulator for the dynamic restoration of ovarian tissue in cryopreservation and transplantation.

The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain.

Short-term outcome of intracorporeal ileocolonic anastomosis in patients with visceral obesity.

The primary objective of this study was to compare short-term outcomes between Intracorporeal ileocolic anastomosis (IIA) and extracorporeal ileocolic anastomosis (EIA) after laparoscopic right hemicolectomy in patients with visceral obesity. The secondary objective was to identify risk factors associated with prolonged postoperative ileus (PPOI) after laparoscopic right hemicolectomy. This single-center retrospective study analyzed visceral obesity patients who underwent laparoscopic right hemicolectomy for primary bowel cancer between January 2020 and June 2023. Patients were categorized into IIA and EIA groups based on the type of anastomosis, and a 1:1 propensity score-matched analysis was performed. A total of 129 patients were initially included in this study, with 45 patients in each group following propensity score matching. The IIA group had significantly longer anastomosis times (p < 0.001), shorter incision length (p < 0.001), and shorter length of stay (p = 0.003) than the EIA group. Meanwhile, the IIA group showed a shorter time to first flatus (p = 0.044) and quicker tolerance of a solid diet (p = 0.030). On multivariate analysis, postoperative use of opioid analgesics is an independent risk factor for PPOI (OR: 3.590 95% CI 1.033-12.477, p = 0.044), while IIA is an independent protective factor (OR: 0.195 95% CI 0.045-0.843, p = 0.029). IIA remains a safe and feasible option for visceral obesity patients. It is also associated with a quicker recovery of bowel function and shorter length of stay when compared to EIA. Additionally, IIA is an independent protective factor for PPOI.

A novel antimicrobial peptide S24 combats serious wound infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii.

OBJECTIVES: Pseudomonas aeruginosa and Acinetobacter baumannii are ranked as top-priority organisms by WHO. Antimicrobial peptides (AMPs) are promising antimicrobial agents that are highly effective against serious bacterial infections. METHODS: In our previous study, a series of α-helical AMPs were screened using a novel multiple-descriptor strategy. The current research suggested that S24 exhibited strong antimicrobial activity against major pathogenic bacteria, and displayed minimal haemolysis, good serum stability and maintained salt resistance. RESULTS: We found that S24 exerted an antimicrobial effect by destroying outer membrane permeability and producing a strong binding effect on bacterial genomic DNA that inhibits genomic DNA migration. Furthermore, S24 exerted a strong ability to promote healing in wound infected by P. aeruginosa, A. baumannii and mixed strains in a mouse model. CONCLUSIONS: Overall, S24 showed good stability under physiological conditions and excellent antimicrobial activity, suggesting it may be a potential candidate for the development of serious bacterial infection treatment.

Importance of computed tomography perfusion on assessing collateral circulation and prognosis of patients with acute anterior circulation large vessel occlusion after endovascular therapy.

This study probed the importance of computed tomography perfusion (CTP) on assessing collateral circulation and prognosis in patients with acute anterior circulation large vessel occlusion (AAC-LVO) after endovascular therapy (EVT). Retrospective analysis was performed on the case data of 124 AAC-LVO patients who achieved EVT in the First People's Hospital of Lianyungang. All patients received computed tomography (CT) examination. Based on the multi-phase computed tomography angiography (mCTA) score, patients were separated into poor collateral circulation group and good collateral circulation group. Based on modified Rankin scale (mRS) score, patients were separated into good prognosis group and poor prognosis group. The receiver operating characteristic (ROC) curve was used to measure the efficacy of CTP parameters in predicting good collateral circulation or good prognosis. Correlation between CTP parameters with mCTA collateral and 90-day mRS circulation score was analyzed using the Spearman correlation analysis. The age and admission national Institutes of Health stroke scale (NIHSS) scores of the good collateral circulation group were lower than the poor collateral circulation group, and low perfusion area volume with Tmax > 6 s (VTmax>6 s), infarct core area volume (VCBF<30 %)and hypoperfusion intensity ratio (HIR) were also lower. The mCTA collateral cycle score was negatively related to VTmax>6s, VCBF<30 % and HIR. The area under the curve (AUC) values of VTmax>6s and VCBF<30 % and HIR for predicting good collateral circulation were 0.763, 0.884 and 0.842, respectively, which suggested that perfusion parameters VTmax>6s, VCBF<30 % and HIR could effectively indicate the status of patients' collateral circulation. Relative to the poor prognosis group, patients in the good prognosis group possessed lower admission NIHSS score, younger age, smaller final infarct volume, lower HIR, VCBF<30 %, VTmax>6 s, Alberta Stroke Program Early CT(ASPECT) score, and higher mCTA score. Spearman correlation analysis unveiled that ASPECT score, mCTA score and 90-day mRS were negatively correlated. The final infarct volume, perfusion parameters HIR and VCBF<30 % were positively correlated with 90-day mRS. ROC analysis showed that all variates had good prognostic value for acute anterior circulation great vessel occlusion patients, while VCBF<30 % and HIR had high diagnostic value for prognosis. To sum up, CTP can provide a comprehensive imaging assessment of the collateral circulation of patients with AAC-LVO and has a higher predictive value for the prognosis assessment of patients with EVT in terms of VCBF<30 %, HIR score and mCTA collateral circulation score.

Population structure in Mixornis tit-babblers across Sunda Shelf matches interfluvia of paleo-rivers.

Rivers constitute an important biogeographic divide in vast areas of tropical rainforest, such as the Amazon and Congo Basins. Southeast Asia's rainforests are currently fragmented across islands divided by sea, which has long obscured their extensive history of terrestrial connectivity as part of a vast (but now submerged) subcontinent - Sundaland - during most of the Quaternary. The role of paleo-rivers in determining population structure in Sundaic rainforests at a time when these forests were connected remains little understood. We examined the coloration of museum skins and used the genomic DNA of museum samples and freshly-collected blood tissue of a pair of Sundaic songbird species, the pin-striped and bold-striped tit-babblers (Mixornis gularis and M. bornensis, respectively), to assess the genetic affinity of populations on small Sundaic islands that have largely been ignored by modern research. Our genomic and morphological results place the populations from the Anambas and Natuna Islands firmly within M. gularis from the Malay Peninsula in western Sundaland, even though some of these islands are geographically much closer to Borneo, where M. bornensis resides. Our results reveal genetic structure consistent with the course of Sundaic paleo-rivers and the location of the interfluvia they formed, and add to a small but growing body of evidence that rivers would have been of equal biogeographic importance in Sundaland's former connected forest landscape as they are in Amazonia and the Congo Basin today.

Distribution and correlation of refractive parameters in children with different corneal curvatures in southeast China.

AIM: To analyze the distribution of refractive status in school-age children with different corneal curvatures (CC) and the correlation between CC and refractive status. METHODS: A total of 2214 school-aged children of grade 4 in Hangzhou who were screened for school myopia were included. Uncorrected distance visual acuity (UCDVA), non-cycloplegic refraction, axial length (AL), horizontal and vertical corneal curvature (K1, K2) were measured and spherical equivalent (SE), corneal curvature radius (CCR) and axial length/corneal radius of curvature ratio (AL/CR) were calculated. UCDVA<5.0 and SE≤-0.50 D were classified as school-screening myopia. According to the different CCRs, the patients were divided into the lower corneal curvature (LCC) group (CCR≥7.92) and the higher corneal curvature (HCC) group (CCR<7.92). Each group was further divided into the normal AL subgroup and the long AL subgroup. The refractive parameters were compared to identify any differences between the two groups. RESULTS: Both SE and AL were greater in the LCC group (P=0.013, P<0.001). The prevalence of myopia was 38% in the LCC group and 44% in the HCC group (P<0.001). The proportion of children without screening myopia was higher in the LCC group (62%) than in the HCC group (56%). Among these children without screening myopia, the proportion of long AL in the LCC group (24%) was significantly higher than that in the HCC group (0.012%; P<0.001). The change of SE in the LCC group was less affected by the increase of AL than that in the HCC group. CONCLUSION: School-aged children in the LCC group have a lower incidence of screening myopia and longer AL. Low CC can mask SE reduction and AL growth to some extent, and the change of AL growth change more in children with low CC than high CC. Before the onset of myopia, its growth rate is even faster than that after the onset of myopia.

[Simultaneous determination of seven artemisinin-related compounds in Artemisia annua by UPLC-QQQ-MS/MS].

A variety of compounds in Artemisia annua were simultaneously determined to evaluate the quality of A. annua from multiple perspectives. A method based on ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QQQ-MS/MS) was established for the simultaneous determination of seven compounds: amorpha-4,11-diene, artemisinic aldehyde, dihydroartemisinic acid, artemisinic acid, artemisinin B, artemisitene, and artemisinin, in A. annua. The content of the seven compounds in different tissues(roots, stems, leaves, and lateral branches) of A. annua were compared. The roots, stems, leaves, and lateral branches of four-month-old A. annua were collected and the content of seven artemisinin-related compounds in different tissues was determined. A multi-reaction monitoring(MRM) acquisition mode of UPLC-QQQ-MS/MS was used, with a positive ion mode of atmospheric pressure chemical ion source(APCI). Chromatographic separation was achieved on an Eclipse Plus RRHD C_(18) column(2.1 mm×50 mm, 1.8 µm). The gradient elution was performed with the mobile phase consisted of formic acid(0.1%)-ammonium formate(5 mmol·L~(-1))(A) and the methanol(B) gradient program of 0-8 min, 55%-100% B, 8-11 min, 100% B, and equilibrium for 3 min, the flow rate of 0.6 mL·min~(-1), the column temperature of 40 ℃, the injection volume of 5 µL, and the detection time of 8 min. Through methodological investigation, a method based on UPLC-QQQ-MS/MS was established for the simultaneous quantitative determination of seven representative compounds involved in the biosynthesis of artemisinin. The content of artemisinin in A. annua was higher than that of artemisinin B, and the content of artemisinin and dihydroartemisinic acid were high in all the tissues of A. annua. The content of the seven compounds varied considerably in different tissues, with the highest levels in the leaves and neither artemisinene nor artemisinic aldehyde was detected in the roots. In this study, a quantitative method based on UPLC-QQQ-MS/MS for the simultaneous determination of seven representative compounds involved in the biosynthesis of artemisinin was established, which was accurate, sensitive, and highly efficient, and can be used for determining the content of artemisinin-related compounds in A. annua, breeding new varieties, and controlling the quality of Chinese medicinal materials.

Analysis of the expression level and predictive value of CLEC16A|miR-654-5p|RARA regulatory axis in the peripheral blood of patients with ischemic stroke based on biosignature analysis.

Introduction: Ischemic stroke (IS) is a cerebrovascular disease that can be disabling and fatal, and there are limitations in the clinical treatment and prognosis of IS. It has been reported that changes in the expression profile of circRNAs have been found during injury in ischemic stroke, and circRNAs play an important role in the IS cascade response. However, the specific mechanisms involved in the pathogenesis of IS are not yet fully understood, and thus in-depth studies are needed. Methods: In this study, one circRNA dataset (GSE161913), one miRNA dataset (GSE60319) and one mRNA dataset (GSE180470) were retrieved from the Gene Expression Omnibus (GEO) database and included, and the datasets were differentially expressed analyzed by GEO2R and easyGEO to get the DEcircRNA, DEmiRNA and DEmRNA, and DEmRNA was enriched using ImageGP, binding sites were predicted in the ENCORI database, respectively, and the competitive endogenous RNA (ceRNA) regulatory network was visualized by the cytoscape software, and then selected by MCC scoring in the cytoHubba plugin Hub genes. In addition, this study conducted a case-control study in which blood samples were collected from stroke patients and healthy medical examiners to validate the core network of ceRNAs constructed by biosignature analysis by real-time fluorescence quantitative qRT-PCR experiments. Results: A total of 233 DEcircRNAs, 132 DEmiRNAs and 72 DEmRNAs were screened by bioinformatics analysis. circRNA-mediated ceRNA regulatory network was constructed, including 148 circRNAs, 43 miRNAs and 44 mRNAs. Finally, CLEC16A|miR-654-5p|RARA competitive endogenous regulatory axis was selected for validation by qRT-PCR, and the validation results were consistent with the bioinformatics analysis. Discussion: In conclusion, the present study establishes a new axis of regulation associated with IS, providing new insights into the pathogenesis of IS.

Searching for Two-Neutrino and Neutrinoless Double Beta Decay of

^{134}Xe is a candidate isotope for neutrinoless double beta decay (0νßß) search. In addition, the two-neutrino case (2νßß) allowed by the standard model of particle physics has not yet been observed. With the 656-kg natural xenon in the fiducial volume of the PandaX-4T detector, which contains 10.4% of ^{134}Xe, and its initial 94.9-day exposure, we have established the most stringent constraints on 2νßß and 0νßß of ^{134}Xe half-lives, with limits of 2.8×10^{22} yr and 3.0×10^{23} yr at 90% confidence level, respectively. The 2νßß (0νßß) limit surpasses the previously reported best result by a factor of 32 (2.7), highlighting the potential of large monolithic natural xenon detectors for double beta decay searches.

Acid Promoted Tetrafunctionalization of Terminal Alkynes: Geminal Diazidation and Dibromination.

The synthesis of complex alkanes by the tetrafunctionalization of alkynes is limited and challenging. Herein, an unprecedented efficient geminal diazidation and dibromination of terminal alkynes is developed, which provides novel access to structurally diverse organic azides. The approach has exclusive chemo- and regioselectivity and features mild reaction conditions, good tolerance of various functional groups, and more crucially, no metal involved in the reaction, thereby benefiting the late-stage decoration of medicinal molecules. A mechanistic study showed that the current geminal diazidation and dibromination proceeds via a radical pathway.

A novel immune­related lncRNA as a prognostic biomarker in HER2+ breast cancer.

Human epidermal growth factor receptor 2 (HER2)+ breast cancer is characterized by high malignancy and poor prognosis. Long non-coding (lnc)RNAs are crucial in breast cancer progression and prognosis, especially in tumor-associated immune processes. The present study aimed to elucidate novel lncRNAs related to immune function that could serve as biomarkers for both diagnosis and prognosis of this cancer subtype. Using data from The Cancer Genome Atlas and The Immunology Database and Analysis Portal, correlation analysis was performed to identify differentially expressed lncRNAs and immune-related genes. Through receiver operating characteristic analysis, the diagnostic value of specific lncRNAs was identified and evaluated, with a focus on their capacity to distinguish between cancerous and non-cancerous states. The present research revealed 22 differentially expressed lncRNAs and 23 differentially expressed immune-related genes, with 19 immune-related lncRNAs. A total of 13 of these lncRNAs demonstrated diagnostic relevance. In particular, it was demonstrated that the expression of lncRNA CTC-537E7.2 was significantly correlated with patient survival, suggesting its potential as a prognostic marker. Additionally, the expression of lncRNA CTC-537E7.2 was significantly correlated with clinical parameters, such as hormone receptor status and patient demographics. Moreover, it exhibited associations with four distinct immune cell types and demonstrated involvement in the Janus kinase-signal transducer and activator of transcription pathway. Further assessment by in situ hybridization confirmed the increased expression of lncRNA CTC-537E7.2 in samples from HER2+ patients, reinforcing its significance. In summary, the present study uncovered a novel prognostic biomarker for HER2+ breast cancer, thereby laying the groundwork for investigating the underlying molecular mechanisms driving the development of this subtype of breast cancer.

Antihypertensive treatment during pregnancy induces long-term changes in gut microbiota and the behaviors of the attention deficit hyperactivity disorder offspring.

The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) has not been fully elucidated. Gestational hypertension could double the probability of ADHD in the offspring, while the initial bacterial communication between the mother and offspring has been associated with psychiatric disorders. Thus, we hypothesize that antihypertensive treatment during pregnancy may abate the impairments in neurodevelopment of the offspring. To test this hypothesis, we chose Captopril and Labetalol, to apply to pregnant spontaneously hypertensive rat (SHR) dams and examined the outcomes in the male offspring. Our data demonstrated that maternal treatment with Captopril and Labetalol had long-lasting changes in gut microbiota and behavioral alterations, including decreased hyperactivity and increased curiosity, spatial learning and memory in the male offspring. Increased diversity and composition were identified, and some ADHD related bacteria were found to have the same change in the gut microbiota of both the dam and offspring after the treatments. LC-MS/MS and immunohistochemistry assays suggested elevated expression of brain derived neurotrophic factor (BDNF) and dopamine in the prefrontal cortex and striatum of offspring exposed to Captopril/ Labetalol, which may account for the improvement of the offspring's psychiatric functions. Therefore, our results support the beneficial long-term effects of the intervention of gestational hypertension in the prevention of ADHD.

Discovery of novel diaryl substituted isoquinolin-1(2H)-one derivatives as hypoxia-inducible factor-1 signaling inhibitors for the treatment of rheumatoid arthritis.

Since synovial hypoxic microenvironment significantly promotes the pathological progress of rheumatoid arthritis (RA), hypoxia-inducible factor 1 (HIF-1) has been emerged as a promising target for the development of novel therapeutic agents for RA treatment. In this study, we designed and synthesized a series of diaryl substituted isoquinolin-1(2H)-one derivatives as HIF-1 signaling inhibitors using scaffold-hopping strategy. By modifying the substituents on N-atom and 6-position of isoquinolin-1-one, we discovered compound 17q with the most potent activities against HIF-1 (IC50 = 0.55 µM) in a hypoxia-reactive element (HRE) luciferase reporter assay. Further pharmacological studies revealed that 17q concentration-dependently blocked hypoxia-induced HIF-1α protein accumulation, reduced inflammation response, inhibited cellular invasiveness and promoted VHL-dependent HIF-1α degradation in human RA synovial cell line. Moreover, 17q improved the pathological injury of ankle joints, decreased angiogenesis and attenuated inflammation response in the adjuvant-induced arthritis (AIA) rat model, indicating the promising therapeutic potential of compound 17q as an effective HIF-1 inhibitor for RA therapy.