Functional dissection of parabrachial substrates in processing nociceptive information.

Painful stimuli elicit first-line reflexive defensive reactions and, in many cases, also evoke second-line recuperative behaviors, the latter of which reflects the sensing of tissue damage and the alleviation of suffering. The lateral parabrachial nucleus (lPBN), composed of external- (elPBN), dorsal- (dlPBN), and central/superior-subnuclei (jointly referred to as slPBN), receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption. However, the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear. In this study, we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor ( NK1R) (lPBN NK1R) are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle, while elPBN neurons are dispensable for driving such reactions. Notably, lPBN NK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats. Lastly, both lPBN NK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions. Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.

Bone transport induces the release of factors with multi-tissue regenerative potential for diabetic wound healing in rats and patients.

Tibial cortex transverse distraction is a surgical method for treating severe diabetic foot ulcers (DFUs), but the underlying mechanism is unclear. We show that antioxidant proteins and small extracellular vesicles (sEVs) with multiple-tissue regenerative potential are released during bone transport (BT) in humans and rats. These vesicles accumulate in diabetic wounds and are enriched with microRNAs (miRNAs) (e.g., miR-494-3p) that have high regenerative activities that improve the circulation of ischemic lower limbs while also promoting neovascularization, fibroblast migration, and nerve fiber regeneration. Deletion of miR-494-3p in rats reduces the beneficial effects of BT on diabetic wounds, while hydrogels containing miR-494-3p and reduced glutathione (GSH) effectively repair them. Importantly, the ginsenoside Rg1 can upregulate miR-494-3p, and a randomized controlled trial verifies that the regimen of oral Rg1 and GSH accelerates wound healing in refractory DFU patients. These findings identify potential functional factors for tissue regeneration and suggest a potential therapy for DFUs.

Photoacoustic Imaging-Guided Self-Adaptive Hyperthermia Supramolecular Cascade Nano-Reactor for Diabetic Periodontal Bone Regeneration.

Commencing with the breakdown of the diabetic osteoimmune microenvironment, multiple pathogenic factors, including hyperglycemia, inflammation, hypoxia, and deleterious cytokines, are conjointly involved in the progression of diabetic periodontal bone regeneration. Based on the challenge of periodontal bone regeneration treatment and the absence of real-time feedback of blood oxygen fluctuation in diabetes mellitus, a novel self-adaptive hyperthermia supramolecular cascade nano-reactor ACFDG is constructed via one-step supramolecular self-assembly strategy to address multiple factors in diabetic periodontal bone regeneration. Hyperthermia supramolecular ACFDG possesses high photothermal conversion efficiency (32.1%), and it can effectively inhibit the vicious cycle of ROS-inflammatory cascade through catalytic cascade reactions, up-regulate the expression of heat shock proteins (HSPs) under near-infrared (NIR) irradiation, which promotes periodontal bone regeneration. Remarkably, ACFDG can provide real-time non-invasive diagnosis of blood oxygen changes during periodontal bone regeneration through photoacoustic (PA) imaging, thus can timely monitor periodontal hypoxia status. In conclusion, this multifunctional supramolecular nano-reactor combined with PA imaging for real-time efficacy monitoring provides important insights into the biological mechanisms of diabetic periodontal bone regeneration and potential clinical theranostics.

Icaritin-curcumol activates CD8+ T cells through regulation of gut microbiota and the DNMT1/IGFBP2 axis to suppress the development of prostate cancer.

BACKGROUND: Prostate cancer (PCa) incidence and mortality rates are rising. Our previous research has shown that the combination of icariin (ICA) and curcumol (CUR) induced autophagy and ferroptosis in PCa cells, and altered lipid metabolism. We aimed to further explore the effects of the combination of ICA and CUR on gut microbiota, metabolism, and immunity in PCa. METHODS: A mouse subcutaneous RM-1 cell tumor model was established. 16 S rRNA sequencing was performed to detect changes in fecal gut microbiota. SCFAs in mouse feces, and the effect of ICA-CUR on T-cell immunity, IGFBP2, and DNMT1 were examined. Fecal microbiota transplantation (FMT) was conducted to explore the mechanism of ICA-CUR. Si-IGFBP2 and si/oe-DNMT1 were transfected into RM-1 and DU145 cells, and the cells were treated with ICA-CUR to investigate the mechanism of ICA-CUR on PCa development. RESULTS: After treatment with ICA-CUR, there was a decrease in tumor volume and weight, accompanied by changes in gut microbiota. ICA-CUR affected SCFAs and DNMT1/IGFBP2/EGFR/STAT3/PD-L1 pathway. ICA-CUR increased the positive rates of CD3+CD8+IFN-γ, CD3+CD8+Ki67 cells, and the levels of IFN-γ and IFN-α in the serum. After FMT (with donors from the ICA-CUR group), tumor volume and weight were decreased. SCFAs promote tumor development and the expression of IGFBP2. In vitro, DNMT1/IGFBP2 promotes cell migration and proliferation. ICA-CUR inhibits the expression of DNMT1/IGFBP2. CONCLUSIONS: ICA-CUR mediates the interaction between gut microbiota and the DNMT1/IGFBP2 axis to inhibit the progression of PCa by regulating immune response and metabolism, suggesting a potential therapeutic strategy for PCa.

Three-Dimensional Printable Magnetic Microfibers: Development and Characterization for Four-Dimensional Printing.

This study proposes a novel and simple fabrication method of magnetic microfibers, employing filament stretching three-dimensional (3D) printing, and demonstrates the capacity of four-dimensional (4D) printing of the proposed magnetic microfibers. A ferromagnetic 3D printing filament is prepared by the mixture of neodymium-iron-boron (NdFeB) and polylactic acid (PLA), and we investigate the characteristics of the ferromagnetic filament by mixing ratio, magnetic properties, mechanical properties, and rheological properties through experiments. By thermal extrusion of the ferromagnetic filament through a 3D printer nozzle, various thicknesses (80-500 µm) and lengths (less than ∼5 cm) of ferromagnetic microfibers are achieved with different printing setups, such as filament extrusion amount and printing speed. The printed ferromagnetic microfibers are magnetized to maintain a permanent magnetic dipole moment, and 4D printing can be achieved by the deformations of the permanently magnetized microfibers under magnetic fields. We observe that the mixing ratio, the thickness, and the length of the magnetized microfibers provide distinct deformation of the microfiber for customization of 4D printings. This study exhibits that the permanently magnetized microfibers have a great potential for smart sensors and actuators. Furthermore, we briefly present an application of our proposed magnetic microfibers for bionic motion actuators with various unique undulating and oscillating motions.

Effect of carboxymethyl chitosan on the storage stability of rice dough during frozen storage.

In this study, we aimed to determine the effect of carboxymethyl chitosan (CMCh) and carboxymethyl cellulose sodium (CMCNa) on the quality of frozen rice dough. We used a variety of methods to conduct a thorough investigation of frozen rice dough, including nuclear magnetic resonance (NMR), scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy, size exclusion high-performance liquid chromatography (SE-HPLC), X-ray diffraction (X-RD), differential scanning calorimetry (DSC), and rapid visco analyzer (RVA). Our findings showed that frozen storage caused significant damage to the texture of rice dough, and this damage was reduced by the inclusion of CMCh, which led to a gradual change in the orderly structure of proteins. The degree of cross-linking between CMCh-B (DS:1; 0.5 %, 1 %, and 1.5 %) and the large protein polymer was significantly higher than that between CMCh-A (DS:0.8; 0.5 %, 1 %, and 1.5 %) and CMCNa (DS:1; 1 %), which decreased the ability of bound water to become free water. This resulted in the increase of tan δ, which effectively delayed the structural transformation of frozen rice dough. Furthermore, the introduction of CMCh delayed the immediate order of starch and crystal structure modifications, altering the thermal properties and pasting qualities of the frozen rice dough. Therefore, 1.5 % CMCh-B showed the best protective effect on frozen rice dough.

Elesclomol-copper synergizes with imidazole ketone erastin by promoting cuproptosis and ferroptosis in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) encompass a collection of clonal hematopoietic malignancies distinguished by the depletion of peripheral blood cells. The treatment of MDS is hindered by the advanced age of patients, with a restricted repertoire of drugs currently accessible for therapeutic intervention. In this study, we found that ES-Cu strongly inhibited the viability of MDS cell lines and activated cuproptosis in a copper-dependent manner. Importantly, ferroptosis inducer IKE synergistically enhanced ES-Cu-mediated cytotoxicity both in vitro and in vivo. Of note, the combination of IKE and ES-Cu intensively impaired mitochondrial homeostasis with increased mitochondrial ROS, MMP hyperpolarized, down-regulated iron-sulfur proteins and declined oxygen consumption rate. Additionally, ES-Cu/IKE treatment could enhance the lipoylation-dependent oligomerization of the DLAT. To elucidate the specific order of events in the synergistic cell death, inhibitors of ferroptosis and cuproptosis were utilized to further characterize the basis of cell death. Cell viability assays showed that the glutathione and its precursor N-acetylcysteine could significantly rescue the cell death under either mono or combination treatment, demonstrating that GSH acts at the crossing point in the regulation network of cuproptosis and ferroptosis. Significantly, the reconstitution of xCT expression and knockdown of FDX1 cells have been found to contribute to the tolerance of mono treatment but have little recovery impact on the combined treatment. Collectively, these findings suggest that a synergistic interaction leading to the induction of multiple programmed cell death pathways could be a promising approach to enhance the effectiveness of therapy for MDS.

Fabrication of controlled porous and ultrafast dissolution porous microneedles by organic-solvent-free ice templating method.

Porous Microneedles (PMNs) have been widely used in drug delivery and medical diagnosis owing to their abundant interconnected pores. However, the mechanical strength, the use of organic solvent, and drug loading capacity have long been challenging. Herein, a novel strategy of PMNs fabrication based on the Ice Templating Method is proposed that is suitable for insoluble, soluble, and nanosystem drug loading. The preparation process simplifies the traditional microneedle preparation process with a shorter preparation time. It endows the highly tunable porous morphology, enhanced mechanical strength, and rapid dissolution performance. Micro-CT three-dimensional reconstruction was used to better quantify the internal structures of PMNs, and we further established the equivalent pore network model to statistically analyze the internal pore structure parameters of PMNs. In particular, the mechanical strength is mainly negatively correlated with the surface porosity, while the dissolution velocity is mainly positively correlated with the permeability coefficient by the correlation heatmap. The poorly water-soluble Asiatic acid was encapsulated in PMNs in nanostructured lipid carriers, showing prominent hypertrophic scar healing trends. This work offers a quick and easy way of preparation that may be used to expand PMNs function and be introduced in industrial manufacturing development.

Biogated mesoporous silica nanoagents for inhibition of cell migration and combined cancer therapy.

Migration is an initial step in tumor expansion and metastasis; suppressing cellular migration is beneficial to cancer therapy. Herein, we designed a novel biogated nanoagents that integrated the migration inhibitory factor into the mesoporous silica nanoparticle (MSN) drug delivery nanosystem to realize cell migratory inhibition and synergistic treatment. Antisense oligonucleotides (Anti) of microRNA-330-3p, which is positively related with cancer cell proliferation, migration, invasion, and angiogenesis, not only acted as the locker for blocking drugs but also acted as the inhibitory factor for suppressing migration via gene therapy. Synergistic with gene therapy, the biogated nanoagents (termed as MSNs-Gef-Anti) could achieve on-demand drug release based on the intracellular stimulus-recognition and effectively kill tumor cells. Experimental results synchronously demonstrated that the migration suppression ability of MSNs-Gef-Anti nanoagents (nearly 30%) significantly contributed to cancer therapy, and the lethality rate of the non-small-cell lung cancer was up to 70%. This strategy opens avenues for realizing efficacious cancer therapy and should provide an innovative way for pursuing the rational design of advanced nano-therapeutic platforms with the combination of cancer cell migratory inhibition.

Parental Factors Associated with COVID-19 Vaccine Uptake for Children over 5 Years of Age in Texas.

The COVID-19 vaccine is safe and effective for children, yet parental hesitancy towards vaccinating children against the virus persists. We conducted a telephone-administered weighted survey in Texas to examine parents' sociodemographic factors and medical conditions associated with COVID-19 vaccination intention for parents with unvaccinated children ages 5-17 years. We collected responses from 19,502 participants, of which 4879 were parents of children ages 5-17 years. We conducted multiple logistic regression with Lasso-selected variables to identify factors associated with children's vaccination status and parents' intention to vaccinate their children. From the unweighted sample, less than half of the parents (46.8%) had at least one unvaccinated child. These parents were more likely to be White, English-speaking, not concerned about illness, privately insured, and unvaccinated for COVID-19 themselves (p < 0.001). In the adjusted regression model, parents who were unvaccinated (vs. having COVID-19 booster, aOR = 28.6) and financially insecure (aOR = 1.46) had higher odds of having unvaccinated children. Parents who were Asian (aOR = 0.50), Black (aOR = 0.69), Spanish-speaking (aOR = 0.57), concerned about illness (aOR = 0.63), had heart disease (aOR = 0.41), and diabetes (aOR = 0.61) had lower odds of having unvaccinated children. Parents who were Asian, Black, Hispanic, Spanish-speaking, concerned about illness for others, and vaccine-boosted were more likely to have vaccination intention for their children (p < 0.001). Children's vaccination is essential to reduce COVID-19 transmission. It is important to raise awareness about the value of pediatric COVID-19 vaccination while considering parents' sociodemographic and medical circumstances.

Enhancing the catalytic H2 production performance of magnetic Ni-Fe2O3-C catalyst in biomass steam gasification using electromagnetic induction heating.

In this study, a novel magnetic Ni-Fe2O3-C catalyst combined with electromagnetic induction heating in biomass steam gasification was proposed to enhance H2 production. Better catalytic performance for H2 production was observed with the Ni-Fe2O3-C catalyst under induction heating, resulting in an increase in H2 yield from 735.1 to 2271.2 mL/g-biomass (a 209.1 % enhancement). SEM, TGA and XRD analysis demonstrated a significant decrease in coking deposition, caking, and particle agglomeration of the Ni-Fe2O3-C catalyst under induction heating, while maintaining more active sites. Importantly, the benefits of induction heating were also applicable to different magnetic catalysts like Ni-Al2O3-C, Ni-ZrO2-C, and Ni-MgO-C. Experimental results revealed a logarithmic correlation between the increase in H2 yields due to induction heating and the magnetic saturation (Ms) of the catalysts. The Ni-Fe2O3-C catalyst, with a high Ms of 50.9 emu/g, showed the highest catalytic activity for H2 production under induction heating in this study.

Recognition and detection of histamine in foods using aptamer modified fluorescence polymer dots sensors.

Histamine has been known as a momentous cause of biogenic amine poisoning. Therefore, the content of histamine in foods is strictly required to be controlled within a certain range. Here, an aptamer fluorescent sensor was developed for detection of histamine. Poly [(9, 9-di-n-octylfluorenyl-2, 7-diyl)-alt-(benzo [2,1,3] thiadia-zol-4, 8-diyl)] (PF8BT) and the styrene maleic anhydride copolymer (PSMA) were used for the preparation of PF8BT-Polymer dots (PF8BT-Pdots). PF8BT-Pdots and the cyanine3-phosphoramidite (Cy3) were linked through aptamer to achieve the ratiometric detection for histamine. PF8BT-Pdots were partly quenched by Cy3 due to the fluorescence resonance energy transfer (FRET), when the histamine molecule was recognized by aptamer on the surface of PF8BT-Pdots. A linear range (3-21 µmol/L) was obtained for histamine detection with a low limit of detection (LOD = 0.38 µmol/L). PF8BT aptamer Pdots (PF8BT-A) were used to detect histamine in simply treated aquaculture water and tuna. The cell imaging of HeLa cells presented a good biosecurity and outstanding fluorescent imaging capability of PF8BT-A. The aptamer fluorescent sensors provided a new platform for rapid and accurate detection of histamine in aquatic products and had great potential for the application in food safety and quality control.

Long non-coding RNAs as modulators and therapeutic targets in non-alcoholic fatty liver disease (NAFLD) / RNA largos no codificantes como moduladores y dianas terapéuticas en la enfermedad del hígado graso no alcohólico (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world, with epidemiological studies indicating a 25% prevalence. NAFLD is considered to be a progressive disease that progresses from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH), then to liver fibrosis, and finally to cirrhosis or hepatocellular carcinoma (HCC). Existing research has mostly elucidated the etiology of NAFLD, yet its particular molecular processes remain uncertain. Long non-coding RNAs (LncRNAs) have been linked in a wide range of biological processes in recent years, with the introduction of microarray and high-throughput sequencing technologies, and previous studies have established their tight relationship with several stages of NAFLD development. Existing studies have shown that lncRNAs can regulate the signaling pathways related to hepatic lipid metabolism, NASH, NASH-related fibrosis and HCC. This review aims to provide a basic overview of NAFLD and lncRNAs, summarize and describe the mechanisms of lncRNAs action involved in the development of NAFLD, and provide an outlook on the future of lncRNAs-based therapy for NAFLD. (AU)

La enfermedad del hígado graso no alcohólico (NAFLD) es la enfermedad hepática más común en el mundo, con estudios epidemiológicos que indican una prevalencia del 25%. La NAFLD se considera una enfermedad progresiva que avanza de esteatosis hepática simple a esteatohepatitis no alcohólica (NASH), luego a fibrosis hepática y, finalmente, a cirrosis o carcinoma hepatocelular (HCC). La investigación existente ha dilucidado principalmente la etiología de NAFLD. Sin embargo, sus procesos moleculares particulares siguen siendo inciertos. Los ARN largos no codificantes (lncRNA) se han relacionado en una amplia gama de procesos biológicos en los últimos años, con la introducción de microarrays y tecnologías de secuenciación de alto rendimiento, y estudios previos han establecido su estrecha relación con varias etapas del desarrollo de NAFLD. Los estudios existentes han demostrado que los lncRNA pueden regular las vías de señalización relacionadas con el metabolismo lipídico hepático, NASH, fibrosis relacionada con NASH y HCC. Esta revisión tiene como objetivo proporcionar una visión general básica de NAFLD y lncRNA, resumir y describir los mecanismos de acción de lncRNA involucrados en el desarrollo de NAFLD, y proporcionar una perspectiva sobre el futuro de la terapia basada en lncRNA para NAFLD. (AU)

High-performance Pyroelectric Property Accompanied by Spin Crossover in a Single Crystal of Fe(II) Complex.

Pyroelectric materials hold significant potential for energy harvesting, sensing, and imaging applications. However, achieving high-performance pyroelectricity across a wide temperature range near room temperature remains a significant challenge. Herein, we demonstrate a single crystal of Fe(II) spin-crossover compound shows remarkable pyroelectric properties accompanied by a thermally controlled spin transition. In this material, the uniaxial alignment of polar molecules results in a polarization of the lattice. As the molecular geometry is modulated during a gradual spin transition, the polar axis experiences a colossal thermal expansion with a coefficient of 796×10-6 K-1. Consequently, the material's polarization undergoes significant modulation as a secondary pyroelectric effect. The considerable shift in polarization (pyroelectric coefficient, p=3.7-22 nC K-1cm-2), coupled with a low dielectric constant (ϵ'=4.4-5.4) over a remarkably wide temperature range of 298 to 400 K, suggests this material is a high-performance pyroelectric. The demonstration of pyroelectricity combined with magnetic switching in this study will inspire further investigations in the field of molecular electronics and magnetism.

Case report: Rare case of a preoperatively diagnosed spermatic cord paraganglioma and literature review.

Paraganglioma (PGL) is rare, and PGL that arises from the urogenital system is even rarer. Here we report a case of PGL in spermatic cord and review the relevant literatures. We encountered a 15-year-old boy with a history of hypertension for almost 2 years, accompanied with headache and palpitations. His serum and urine catecholamines were elevated, but no adrenal lesions were detected, suggesting the existence of PGL. Upon physical examination, a painless nodule adherent to the spermatic cord in the right scrotum was found. A systemic Ga68 DOTATATE PET-CT was then performed, and it revealed a mass with high DOTATATE uptake in the right scrotum. The CT, MRI, and ultrasound images showed the abundant blood supply to the tumor. Based on the above-mentioned imaging and biochemical information, a diagnosis of PGL was made prior to surgery. After 2 weeks of preparation with Cardura, an open surgery was performed to remove the tumor together with the right testis and right epididymis. The blood pressure increased to 180/100 mmHg when the tumor was touched intraoperatively and decreased to 90/55 mmHg after the tumor was removed. Post-operative pathology confirmed our diagnosis of PGL originating from the spermatic cord. Immunohistochemical (IHC) staining showed SDHB (+), CgA (+), synaptophysin (+), GATA3 (+), CD56 (+), sertoli cells S-100 (+), and Ki67 (5%). Genetic testing revealed a missense mutation in the SDHA gene. Only 16 cases of spermatic cord PGL have been reported to date. Although it is easy to diagnose by histology and IHC examinations, preoperative diagnosis is quite important as it can actually reduce intraoperative complications.

MicroRNA-30a inhibits cell proliferation in a sepsis-induced acute kidney injury model by targeting the YAP-TEAD complex.

Background: Acute kidney injury (AKI) is a primary feature of renal complications in patients with sepsis. MicroRNA (miRNA/miR)-30a is an essential regulator of cardiovascular diseases, tumors, phagocytosis, and other physical processes, but whether it participates in sepsis-induced AKI (sepsis-AKI) is unknown. We aimed to elucidate the functions and molecular mechanism underlying miR-30a activity in sepsis-AKI. Methods: The classical cecal ligation and puncture (CLP) method and lipopolysaccharide (LPS)-induced Human Kidney 2 (HK-2) cells were used to establish in vivo and in vitro sepsis-AKI models. Specific pathogen-free and mature male Sprague-Dawley (SD) rats, aged 6-8 weeks (weight 200-250 g), were randomly divided into five-time phase subgroups. Fluid resuscitation with 30 mL/kg 37 °C saline was administered after the operation, without antibiotics. Formalin-fixed, paraffin-embedded kidney sections were stained with hematoxylin and eosin. SD rat kidney tissue samples were collected for analysis by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. HK-2 cells were transfected with hsa-miR-30a-3p mimics or inhibitors, and compared with untreated normal controls. RNA, protein, and cell viability were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blot, and cell counting kit-8 methods. A Dual-Luciferase Assay Kit (Promega) was used to measure luciferase activity 48 h after transfection with miR-30a-3p mimics. Results: Expression levels of miR-30a-3p and miR-30a-5p in renal tissues of the sepsis group were significantly reduced at 12 h and 24 h (P <0.05). Tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were significantly increased in renal tissue 3 h after the operation in rats (P <0.05), and gradually decreased 6 h, 12 h, and 24 h after CLP. Levels of miR-30a-5p and miR-30a-3p were significantly down-regulated at 3 h after LPS treatment (P <0.05), and gradually decreased in HK-2 cells. One hour after LPS (10 µg/mL) treatment, TNF-α and IL-1ß levels in HK-2 cells were significantly up-regulated (P < 0.05), and they were markedly down-regulated after 3 h (P <0.05). IL-6 expression levels began to rise after LPS treatment of cells, peaked at 6 h (P <0.05), and then decreased to the initial level within a few hours. Stimulation with 10 µg/mL LPS promoted HK-2 cells proliferation, which was inhibited after miR-30a-3p-mimic transfection. Bioinformatics prediction identified 37 potential miR-30a-3p target genes, including transcriptional enhanced associate domain 1 (TEAD1). After transfection of HK-2 cells with miR-30a-3p mimics and miR-30a-3p inhibitor, TEAD1 transcript was significantly up- and down-regulated, respectively (both P <0.05). After LPS treatment (24 h), expression of TEAD1 in the inhibitors group was significantly increased (P <0.01), while that in the mimics group was significantly suppressed (P <0.01). In the dual luciferase reporter experiment, miR-30a-3p overexpression decreased fluorescence intensity (P <0.01) from TEAD1-wt-containing plasmids, but did not influence fluorescence intensity from TEAD1-muta-containing plasmids. LPS may promote HK-2 cells proliferation through the miR-30a-3p/TEAD1 pathway. Conclusion: In a background of expression of inflammatory factors, including TNF-α, IL-1ß, and IL-6, which were transiently increased in the sepsis-AKI model, miR-30a was down-regulated. Down-regulated miR-30a-3p may promote cell proliferation by targeting TEAD1 in LPS-induced HK-2 cells, demonstrating its potential as a biomarker for early sepsis-AKI diagnosis.

Survival outcomes for women with a solitary extracranial metastasis from breast cancer.

BACKGROUND: Aggressive metastasis directed treatment of extracranial oligometastatic breast cancer with the aim of increasing disease-free survival has emerged as a new potential treatment paradigm, however there is currently a lack of data to assist in identifying the subset of patients who will potentially benefit most. This single-institute retrospective cohort study aimed to evaluate survival outcomes for patients with a solitary extracranial metastasis from breast cancer and to assess for significant prognostic factors. METHODS AND MATERIALS: Medical records of 70 female breast cancer patients with a solitary extracranial metastasis actively managed at the Peter MacCallum Cancer Centre (PMCC) Melbourne Campus between 2000 and 2019 were reviewed. Kaplan-Meier curves were used to estimate overall survival (OS), local progression free survival (LPFS) and distant progression free survival (DPFS). RESULTS: Median follow-up period was 9.4 years. The study included 40 hormone receptor positive/HER2 negative (HR+HER2-), 14 hormone receptor positive/HER2 positive (HR+HER2+), 3 hormone receptor negative/HER2 positive (HR-HER2+), 9 triple negative (TNBC) and 4 unclassified breast cancer patients. 5-year OS rate for all patients was 46%, LPFS rate was 56% and DPFS was 20%. Tumour receptor group had a statistically significant association with OS and DPFS rates. TNBC patients had significantly poorer OS and DPFS rates in comparison to HR+HER2-patients. CONCLUSION: Among patients with a solitary extracranial metastasis from breast cancer, TNBC was associated with the poorest OS and DPFS rates. Identification of other significant prognostic factors for oligometastatic breast cancer patients may inform guidelines for metastasis directed treatments.

Identification of Key Genes and Imbalanced SNAREs Assembly in the Comorbidity of Polycystic Ovary Syndrome and Depression.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have increased odds of concurrent depression, indicating that the relationship between PCOS and depression is more likely to be comorbid. However, the underlying mechanism remains unclear. Here, we aimed to use bioinformatic analysis to screen for the genetic elements shared between PCOS and depression. METHODS: Differentially expressed genes (DEGs) were screened out through GEO2R using the PCOS and depression datasets in NCBI. Protein-protein interaction (PPI) network analysis and enrichment analysis were performed to identify the potential hub genes. After verification using other PCOS and depression datasets, the associations between key gene polymorphism and comorbidity were further studied using data from the UK biobank (UKB) database. RESULTS: In this study, three key genes, namely, SNAP23, VTI1A, and PRKAR1A, and their related SNARE interactions in the vesicular transport pathway were identified in the comorbidity of PCOS and depression. The rs112568544 at SNAP23, rs11077579 and rs4458066 at PRKAR1A, and rs10885349 at VTI1A might be the genetic basis of this comorbidity. CONCLUSIONS: Our study suggests that the SNAP23, PRKAR1A, and VTI1A genes can directly or indirectly participate in the imbalanced assembly of SNAREs in the pathogenesis of the comorbidity of PCOS and depression. These findings may provide new strategies in diagnosis and therapy for this comorbidity.

Pollutant removal in an experimental bioretention cell situated in a northern Chinese sponge city.

To assess the viability and effectiveness of bioretention cell in enhancing rainwater resource utilization within sponge cities, this study employs field monitoring, laboratory testing, and statistical analysis to evaluate the water purification capabilities of bioretention cell. Findings indicate a marked purification impact on surface runoff, with removal efficiencies of 59.81% for suspended solids (SS), 39.01% for chemical oxygen demand (COD), 37.53% for ammonia nitrogen (NH3-N), and 30.49% for total phosphorus (TP). The treated water largely complies with rainwater reuse guidelines and tertiary sewage discharge standards. Notably, while previous research in China has emphasized water volume control in sponge city infrastructures, less attention has been given to the qualitative aspects and field-based evaluations. This research not only fills that gap but also offers valuable insights and practical implications for bioretention cell integration into sponge city development. Moreover, the methodology and outcomes of this study serve as a benchmark for future sponge city project assessments, offering guidance to relevant authorities.