A whole-cell platform for discovering synthetic cell adhesion molecules in bacteria.

Developing programmable bacterial cell-cell adhesion is of significant interest due to its versatile applications. Current methods that rely on presenting cell adhesion molecules (CAMs) on bacterial surfaces are limited by the lack of a generalizable strategy to identify such molecules targeting bacterial membrane proteins in their natural states. Here, we introduce a whole-cell screening platform designed to discover CAMs targeting bacterial membrane proteins within a synthetic bacteria-displayed nanobody library. Leveraging the potency of the bacterial type IV secretion system-a contact-dependent DNA delivery nanomachine-we have established a positive feedback mechanism to selectively enrich for bacteria displaying nanobodies that target antigen-expressing cells. Our platform successfully identified functional CAMs capable of recognizing three distinct outer membrane proteins (TraN, OmpA, OmpC), demonstrating its efficacy in CAM discovery. This approach holds promise for engineering bacterial cell-cell adhesion, such as directing the antibacterial activity of programmed inhibitor cells toward target bacteria in mixed populations.

Enhanced IGF-IIRα Expression Exacerbates Lipopolysaccharide-Induced Cardiac Inflammation, Hypertrophy, and Apoptosis Through Calcineurin Activation.

Cardiovascular disease is one of the leading causes of death worldwide and has a high prevalence. Insulin-like growth factor-II receptor α (IGF-IIRα) acts as a stress-inducible negative regulator. This study focused on the substantial impact of heightened expression of IGF-IIRα in cardiac myoblasts and its association with the exacerbation of cardiac dysfunction. Using lipopolysaccharide (LPS)-induced H9c2 cardiac myoblasts as a model for sepsis, we aimed to elucidate the molecular interactions between IGF-IIRα and LPS in exacerbating cardiac injury. Our findings demonstrated a synergistic induction of cardiac inflammation and hypertrophy by LPS stimulation and IGF-IIRα overexpression, leading to decreased cell survival. Excessive calcineurin activity, triggered by this combined condition, was identified as a key factor exacerbating the negative effects on cell survival. Cellular changes such as cell enlargement, disrupted actin filaments, and upregulation of hypertrophy-related and inflammation-related proteins contributed to the overall hypertrophic and inflammatory responses. Overexpression of IGF-IIRα also exacerbated apoptosis induced by LPS in H9c2 cardiac myoblasts. Inhibiting calcineurin in LPS-treated H9c2 cardiac myoblasts with IGF-IIRα overexpression effectively reversed the detrimental effects, reducing cell damage and mitigating apoptosis-related cardiac mechanisms. Our study suggests that under sepsis-like conditions in the heart with IGF-IIRα overexpression, hyperactivation of calcineurin worsens cardiac damage. Suppressing IGF-IIRα and calcineurin expression could be a potential intervention to alleviate the impact of the illness and improve cardiac function.

Pathogenic Detection by Metagenomic Next-generation Sequencing in Skin and Soft Tissue Infection.

BACKGROUND/AIM: Skin and soft tissue infections (SSTIs) can be life-threatening, but the conventional bacterial cultures have low sensitivity and are time-consuming. Metagenomic next-generation sequencing (mNGS) is widely used as a diagnostic tool for detecting pathogens from infection sites. However, the use of mNGS for pathogen detection in SSTIs and related research is still relatively limited. PATIENTS AND METHODS: From January 2020 to October 2021, 19 SSTI samples from 16 patients were collected in a single center (Taichung Veterans General Hospital, Taichung, Taiwan). The clinical samples were simultaneously subjected to mNGS and conventional bacterial culture methods to detect pathogens. Clinical characteristics were prospectively collected through electronic chart review. The microbiological findings from conventional bacterial culture and mNGS were analyzed and compared. RESULTS: The mNGS method detected a higher proportion of multiple pathogens in SSTIs compared to conventional bacterial culture methods. Pseudomonas spp. was among the most commonly identified Gram-negative bacilli using mNGS. Additionally, the mNGS method identified several rare pathogens in patients with SSTIs, including Granulicatella adiacens, Bacillus thuringiensis, and Bacteroides fragilis. Antimicrobial resistance genes were detected in 10 samples (52.6%) using the mNGS method, including genes for extended-spectrum beta-lactamase, Ambler class C ß-lactamases, and carbapenemase. CONCLUSION: mNGS not only plays an important role in the detection of pathogens in soft tissue infections, but also informs clinical professionals about the presence of additional microbes that may be important for treatment decisions. Further studies comparing conventional pathogen culture with the mNGS method in SSTIs are required.

LPA suppresses HLA-DR expression in human melanoma cells: a potential immune escape mechanism involving LPAR1 and DR6-mediated release of IL-10.

While immune checkpoint inhibitors (ICIs) are promising in the treatment of metastatic melanoma, about half of patients do not respond well to them. Low levels of human leukocyte antigen-DR (HLA-DR) in tumors have been shown to negatively influence prognosis and response to ICIs. Lysophosphatidic acid (LPA) is produced in large amounts by melanoma and is abundantly present in the tumor microenvironment. LPA induces the release of various cytokines and chemokines from tumor cells, which affect cancer development, metastasis, and tumor immunity. In the present study, we investigated the role of LPA-induced IL-10 release in regulating HLA-DR expression and the underlying mechanisms in human melanoma cells. We showed that LPA (0.001-10 µM) dose-dependently increased DR6 transcript levels through activating LPAR1 in HEK293T cells. Knockdown of NF-κB1 abrogated the LPA-increased DR6 expression without affecting basal DR6 expression in both A2058 and A375 melanoma cell lines. LPA (10 µM) significantly increased IL-10 transcripts in A2058 and A375 melanoma cells, the effect was abolished by pharmacological inhibition of LPAR1 or knockdown of DR6. We found a statistically significant correlation between the expression of LPAR1, DR6 and IL-10 in human melanoma tissue and an association between increased expression of LPAR1 and reduced effectiveness of ICI therapy. We demonstrated that LPA (10 µM) markedly suppressed HLA-DR expression in both A375 and A2058 melanoma cells via activating the LPAR1-DR6-IL-10 pathway. These data suggest that the LPAR1-DR6-IL-10 autocrine loop could constitute a novel mechanism used by tumor cells to evade immunosurveillance by decreasing HLA-DR expression.

Exploring coral reef benefits: A systematic SEEA-driven review.

Coral reefs are among the most diverse and valuable ecosystems on the planet, providing numerous benefits to human societies, including fisheries, coastal protection, and biodiversity conservation. In order to effectively manage and conserve coral reefs, it is essential to understand the value of the ecosystem services they provide. The System of Environmental-Economic Accounting (SEEA) framework offers a comprehensive approach for accounting for ecosystem services, which can be useful for assessing the value of natural environments. While the validity of SEEA for many marine ecosystems is increasingly acknowledged, there remains a scarcity of studies that have investigated SEEA in the context of coral reef ecosystems. To bridge this gap, this study offers extensive examination and investigates the evolution of coral reef ecosystem service research under the SEEA framework in over nearly three decades, providing a rich dataset for understanding trends and gaps. The research findings reveal interdisciplinary methodological integration in coral reef ecosystem research, incorporating remote sensing, environmental science, ecology, environmental economics, ecological economics, computer science, and citizen science. Across different time periods, within the shared focus of coral reef health and sustainability, there has been a transition from concerns about the impacts of human activities to a concentration on climate change, supported by empirical evidence and case studies. These research results contribute to our better understanding of the value of coral reef ecosystems.

A long section of serpentinized depleted mantle peridotite.

The upper mantle is critical for our understanding of terrestrial magmatism, crust formation, and element cycling between Earth's solid interior, hydrosphere, atmosphere, and biosphere. Mantle composition and evolution have been primarily inferred by surface sampling and indirect methods. We recovered a long (1268-meter) section of serpentinized abyssal mantle peridotite interleaved with thin gabbroic intrusions. We find depleted compositions with notable variations in mantle mineralogy controlled by melt flow. Dunite zones have predominantly intermediate dips, in contrast to the originally steep mantle fabrics, indicative of oblique melt transport. Extensive hydrothermal fluid-rock interaction is recorded across the full depth of the core and is overprinted by oxidation in the upper 200 meters. Alteration patterns are consistent with vent fluid composition in the nearby Lost City hydrothermal field.

Satellite cell-derived TRIM28 is pivotal for mechanical load- and injury-induced myogenesis.

Satellite cells are skeletal muscle stem cells that contribute to postnatal muscle growth, and they endow skeletal muscle with the ability to regenerate after a severe injury. Here we discover that this myogenic potential of satellite cells requires a protein called tripartite motif-containing 28 (TRIM28). Interestingly, different from the role reported in a previous study based on C2C12 myoblasts, multiple lines of both in vitro and in vivo evidence reveal that the myogenic function of TRIM28 is not dependent on changes in the phosphorylation of its serine 473 residue. Moreover, the functions of TRIM28 are not mediated through the regulation of satellite cell proliferation or differentiation. Instead, our findings indicate that TRIM28 regulates the ability of satellite cells to progress through the process of fusion. Specifically, we discover that TRIM28 controls the expression of a fusogenic protein called myomixer and concomitant fusion pore formation. Collectively, the outcomes of this study expose the framework of a novel regulatory pathway that is essential for myogenesis.

Two New Phenylpropanoids and a Polyphenol with Anti-Cervical Cancer Activity from Smilax china L.

Two novel phenylpropanoids (compounds 1 and 2) and 11 known compounds were isolated from Smilax china L. Their structures were determined by NMR (1D and 2D) and high-resolution electrospray ionization mass spectrometry. Further, the cytotoxic activity of all the isolated compounds against HeLa, 4T1, and U251 tumor cells was evaluated using the cell counting kit-8 assay, revealing that compound 13 showed significant cytotoxicity toward HeLa cells. Further investigations explored the impact of compound 13 on the mitochondrial membrane potential, concentration of reactive oxygen species, wound-healing distance, and cell cycle of HeLa cells. Notably, compound 13 significantly decreased mitochondrial membrane potential, suppressed cell migration, and increased intracellular reactive oxygen species levels in HeLa cells. Furthermore, compound 13 inhibited HeLa cell-cycle progression in the S phase. These findings indicate that compound 13 is a potential drug lead for the treatment of cervical cancer.

The transcription factor Tbx5-dependent epigenetic modification contributes to neuropathic allodynia by activating TRPV1 expression in dorsal horn.

Nerve injury can induce aberrant changes in the spine; these changes are due to, or at least partly governed by, transcription factors that contribute to the genesis of neuropathic allodynia. Here, we showed that spinal nerve ligation (SNL, a clinical neuropathic allodynia model) increased the expression of the transcription factor Tbx5 in the injured dorsal horn in male Sprague Dawley rats. In contrast, blocking this upregulation alleviated SNL-induced mechanical allodynia, and there was no apparent effect on locomotor function. Moreover, SNL-induced Tbx5 upregulation promoted the recruitment and interaction of GATA4 and Brd4 by enhancing its binding activity to H3K9Ac, which was enriched at the Trpv1 promotor, leading to an increase in TRPV1 transcription and the development of neuropathic allodynia. In addition, nerve injury-induced expression of Fbxo3, which abates Fbxl2-dependent Tbx5 ubiquitination, promoted the subsequent Tbx5-dependent epigenetic modification of TRPV1 expression during SNL-induced neuropathic allodynia. Collectively, our findings indicated that spinal Tbx5-dependent TRPV1 transcription signaling contributes to the development of neuropathic allodynia via Fbxo3-dependent Fbxl2 ubiquitination and degradation. Thus, we propose a potential medical treatment strategy for neuropathic allodynia by targeting Tbx5.Significance Statement Nerve injury-induced epigenetic changes in Tbx5 enhance TRPV1 expression in the dorsal horn, with Tbx5 recruiting GATA4 and Brd4 for epigenetic modification of TRPV1. The Fbxo3-mediated Fbxl2 ubiquitination pathway stabilizes Tbx5, increasing its transcriptional activity and enhancing TRPV1 expression, contributing to the initiation and maintenance of neuropathic pain via epigenetic reprogramming.

Rapid-Test Kit for Cardiac Troponin I: A Reliable Enzyme-Linked-Immuno-Substrate-Assay-Based Biosensor for Daily-Use Naked-Eye Detection and Pharmacokinetic Studies for Myocardial Infarction in Cardiovascular Disease.

Myocardial infarction (MI) is a severe cardiovascular event that can lead to death. Cardiac troponin I (cTnI) is an MI biomarker in the circulation system; however, methods for detecting cTnI protein require substantial time, tedious operations, an expensive reader for translating signals, and a lot of reagents. This study aims to create a cTnI protein test kit with results easily distinguished by color differences, explicitly focusing on the resolution between different concentrations that eyes can discern. These results will aid in creating a commercial, portable, convenient, daily-use rapid-test kit. This study proposes a cTnI biosensor that the naked eye can perceive, performs diagnoses based on pattern color, does not require a reader machine, is easy to operate, and is portable. Our device shortens diagnosis time, has a 0.32-200 ng/mL quantitative analysis range in the human serum matrix, achieves a 0.32 ng/mL limit of detection, and exhibits many advantages compared to a traditional cTnI ELISA plate.

Phantom energy in the nonlinear response of a quantum many-body scar state.

Quantum many-body scars are notable as nonthermal, low-entanglement states that exist at high energies. Here, we use attractively interacting dysprosium gases to create scar states that are stable enough to be driven into a strongly nonlinear regime while retaining their character. We measure how the kinetic and total energies evolve after quenching the confining potential. Although the bare interactions are attractive, the atoms behave as if they repel each other: Their kinetic energy paradoxically decreases as the gas is compressed. The missing "phantom" energy is quantified by benchmarking our experimental results against generalized hydrodynamics calculations. We present evidence that the missing kinetic energy is carried by undetected, very high-momentum atoms.

Recommendations and guidance for herpes zoster vaccination for adults in Taiwan.

Herpes zoster (HZ) is a painful, vesicular, cutaneous eruption from reactivation of varicella zoster virus (VZV), which can lead to potentially debilitating complications. The lifetime risk of HZ is estimated to be 20%-30% in the general population, with an increased risk in the elderly and immunocompromised populations. The most effective strategy to prevent HZ and its complications is by vaccination. Two types of HZ vaccines, zoster vaccine live and recombinant zoster vaccine, have been approved for use. This guidance offers recommendations and suggestions for HZ vaccination in adults, aiming to reduce the disease burden of HZ and its complications. It is intended as a guide to first-line healthcare providers, but does not supersede clinical judgement when assessing risk and providing recommendations to individuals. The Working Group on Adult Immunization Practice was appointed by the Infectious Diseases Society of Taiwan (IDST) and recommendations were drafted after a full literature review, using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. The recommendations were reviewed and revised by expert review panels during a series of consensus meetings and endorsed by the IDST, Taiwan Association of Family Medicine, the Taiwanese Dermatological Association, the Taiwan Oncology Society, the Taiwan Society of Blood and Marrow Transplantation, the Transplantation Society of Taiwan, the Taiwan AIDS Society, and the Taiwan College of Rheumatology. This guidance describes the epidemiology of HZ and provides recommendations for HZ vaccination in adults with varying levels of risk, differing history of previous VZV infection and past varicella or zoster vaccinations.

Statin therapy enhances survival in unresectable stage III lung squamous cell carcinoma with concurrent chemoradiotherapy.

To evaluate the impact of statin use on overall survival and lung cancer-specific survival in patients with unresectable stage III lung squamous cell carcinoma (LSCC) undergoing standard concurrent chemoradiotherapy (CCRT). Using data from the Taiwan Cancer Registry Database and National Health Insurance Research Database, this propensity score matching cohort study analyzed the influence of statin use during CCRT on overall survival and lung cancer-specific survival. Statin use during CCRT was independently associated with significant improvements in overall survival and lung cancer-specific survival. The adjusted hazard ratio (95% CI) for all-cause mortality in the statin group versus the non-statin group was 0.60 (0.53-0.68, P < 0.0001). Similarly, the adjusted hazard ratio for lung cancer-specific mortality in the statin group versus the non-statin group was 0.61 (95% CI, 0.54-0.70, P < 0.0001). Pravastatin and fluvastatin exhibited the greatest potential in reducing lung cancer-specific mortality among statins, with rosuvastatin following closely behind. Atorvastatin demonstrated comparable effectiveness, while simvastatin and lovastatin displayed lower efficacy in this regard. Furthermore, a dose-response relationship was observed, with higher cumulative defined daily doses and greater daily intensity of statin use associated with reduced mortality. Our study provides evidence that statin use during CCRT for unresectable stage III LSCC is associated with significant improvements in overall survival and lung cancer-specific survival. Pravastatin showed the highest potential for reducing lung cancer-specific mortality among statins, followed by rosuvastatin. Atorvastatin and fluvastatin exhibited similar effectiveness, while simvastatin and lovastatin demonstrated lower efficacy. The dose-response relationship showed higher statin utilization in reducing lung cancer-specific mortality.

Rejuvenation of Meropenem by Conjugation with Tilapia Piscidin-4 Peptide Targeting NDM-1 Escherichia coli.

Gram-negative pathogens that produce ß-lactamases pose a serious public health threat as they can render ß-lactam antibiotics inactive via hydrolysis. This action contributes to the waning effectiveness of clinical antibiotics and creates an urgent need for new antimicrobials. Antimicrobial peptides (AMPs) exhibiting multimodal functions serve as a potential source in spite of a few limitations. Thus, the conjugation of conventional antibiotics with AMPs may be an effective strategy to leverage the advantages of each component. In this study, we conjugated meropenem to the AMP Tilapia piscidin 4 (TP4) using a typical coupling reaction. The conjugate was characterized by using HPLC-MS, HR-MS, and MS-MS fragmentation analysis. It was then evaluated in terms of antibacterial potency, hemolysis, and cytotoxicity toward RAW264.7 and CCD-966SK cell lines. The conjugation of meropenem with TP4 significantly reduced the cytotoxicity compared to TP4. Conjugation of unprotected TP4 with meropenem resulted in cross-linking at the N-terminal and lysine sites. The structural activity relationship of the two isomers of the TP4-meropenem conjugate was investigated. Both the isomers showed notable antibacterial activities against NDM-1 Escherichia coli and reduced red blood cell hemolysis as compared to TP4. Lysine conjugate (TP4-K-Mero) showed lesser hemolysis than the N-terminal conjugate (TP4-N-Mero). Molecular modeling further revealed that the conjugates can bind to lipopolysaccharides and inhibit NDM-1 ß-lactamase. Together, these data show that conjugation of antibiotics with AMP can be a feasible approach to increase the therapeutic profile and effectively target multidrug-resistant pathogens. Furthermore, antibiotic conjugation at different AMP sites tends to show unique biological properties.

Development of a tightly regulated copper-inducible transient gene expression system in Nicotiana benthamiana incorporating a suicide exon and Cre recombinase.

Chemical-inducible gene expression systems are commonly used to regulate gene expression for functional genomics in various plant species. However, a convenient system that can tightly regulate transgene expression in Nicotiana benthamiana is still lacking. In this study, we developed a tightly regulated copper-inducible system that can control transgene expression and conduct cell death assays in N. benthamiana. We tested several chemical-inducible systems using Agrobacterium-mediated transient expression and found that the copper-inducible system exhibited the least concerns regarding leakiness in N. benthamiana. Although the copper-inducible system can control the expression of some tested reporters, it is not sufficiently tight to regulate certain tested hypersensitive cell death responses. Using the MoClo-based synthetic biology approach, we incorporated the suicide exon HyP5SM/OsL5 and Cre/LoxP as additional regulatory elements to enhance the tightness of the regulation. This new design allowed us to tightly control the hypersensitive cell death induced by several tested leucine-rich repeat-containing proteins and their matching avirulence factors, and it can be easily applied to regulate the expression of other transgenes in transient expression assays. Our findings offer new approaches for both fundamental and translational studies in plant functional genomics.

Investigations on corrosion resistance of steel coated with chromium-free ZTM conversion coating.

Chromium-free conversion coatings based on Zr/Ti/Mo (ZTM) compounds via chemical conversion technology were investigated to improve the corrosion performance of SPCC-JISG 31 steels. A preliminary study was carried out to evaluate the influences of critical parameters, including the concentrations of active species Zr, Ti and Mo, and the conversion bath's pH, on the protective efficiency using a Statistical design of experiments (DoE) methodology. Passivation layer with compositional Mo, Ti and Zr elements has been employed on the steels by dipping in mixed solutions containing 17 g/l Na2MoO4, 1 g/l K2TiF6 and 7 g/l K2ZrF6 under pH = 5. The morphology and elemental analysis of Zr/Ti/Mo on surface of the steels was studied by the employment of scanning electron microscopy with energy dispersive spectroscopy (SEM/EDS). Pull-off adhesion test was performed, indicating that the ZTM coatings enabled to increase the adhesion strength (6.0 MPa) of mild steel to the organic coating than that of traditional phosphate (ZrP) coating. The results of electrochemical impedance spectroscopy and the salt spray test (529 h) evidenced the higher corrosion resistance of the Zr/Ti/Mo coating compared with theconventional phosphate coating.

Altered Abdominal Muscle Recruitment and Declined Physical Function in Postpartum Individuals With Pregnancy-Related Pelvic Girdle Pain: A Matched Case-Control Study.

INTRODUCTION: The influence of pregnancy-related pelvic girdle pain (PPGP) on lumbopelvic muscles has not been comprehensively examined in postpartum individuals. Previous research also presented self-reported activity limitations without objective measures. METHODS: Thirty postpartum individuals with PPGP (PPGP group) and 30 age-, parity-, and postpartum duration-matched asymptomatic individuals (healthy group) were recruited. Transabdominal ultrasonography was used to measure muscle thickness or activation changes of the external oblique (EO), internal oblique (IO), transverse abdominals, lumbar multifidus, and pelvic floor muscles (PFMs) during rest and while performing the active straight leg raise (ASLR). Muscle changes were compared separately in the painful and nonpainful sides between the PPGP and health control group. Physical function was assessed using the ASLR fatigue (ASLRF), timed up-and-go, and 6-m walking (6MW) tests. RESULTS: The PPGP group had greater thickening changes in the bilateral IO during ASLR compared with the healthy group (nonpainful side, 16.34 vs 3.52 mm; P = .010; painful side, 18.83 vs 6.60 mm; P = .02) but became thinner in the EO (nonpainful side, -2.19 vs 19.97 mm; P < .001; painful side, -5.97 vs 21.43 mm; P < .001). Thicker IO and EO on the nonpainful side (IO, 6.60 vs 5.78 mm; P = .004; EO, 5.37 vs 4.54 mm; P = .011) and a lower bladder base (indication of PFMs) (91.87 vs 78.61 mm; P = .002) during rest were also observed in the PPGP group. Furthermore, the performance of the ASLRF and 6MW tests was poorer in the PPGP than in the healthy group (ASLRF nonpainful side, 82.36 vs 59.09 sec; P = .01; painful side, 75.73 vs 59.26 sec; P = .04; 6MW, 3.48 vs 3.17 sec; P = .02). DISCUSSION: Postpartum individuals with PPGP demonstrated altered abdominal muscle recruitment strategies during loading tasks, with objectively impaired physical functions. These findings are critical for developing effective muscle training interventions for PPGP.

Discovery of sesquiterpene lactones with anti-inflammatory effect from Youngia japonica.

The preliminary study revealed that the ethyl acetate eluate of Youngia japonica (YJ-E) could inhibit the expression of key proteins of p-p65, p-IκBα, p-IKKα/ß, and p-AKT in LPS stimulated BV2 cell. Further phytochemical study led to the isolation of eight compounds from YJ-E, including one new sesquiterpene lactone. Their structures were elucidated by several spectroscopic data, and comparing the NMR data of known compound. In addition, all of the isolates were evaluated for the anti-inflammatory effect. As a result, compounds 3 and 4 distinctly attenuated the expressions of p-IκBα, p-p65, and p-AKT in LPS stimulated BV2 cell, respectively.

Transabdominal ultrasonography-guided biofeedback training for pelvic floor muscles integrated with stabilization exercise improved pregnancy-related pelvic girdle pain and disability: a randomized controlled trial.

OBJECTIVES: Investigate effects of integrated training for pelvic floor muscles (PFM) with and without transabdominal ultrasonography (TAUS) imaging-guided biofeedback in postpartum women with pregnancy-related pelvic girdle pain (PPGP). DESIGN: Three-arm, single-blinded randomized controlled trial SETTING: University laboratory PARTICIPANTS: Fifty-three postpartum women with PPGP randomized into stabilization exercise with TAUS-guided biofeedback (BIO+EXE), exercise (EXE), and control (CON) groups. INTERVENTIONS: The BIO+EXE and EXE groups underwent an 8-week exercise program, with the BIO+EXE group receiving additional TAUS-guided biofeedback for PFM training during the first 4 weeks. The CON group only received a pelvic educational session. MAIN OUTCOME MEASURES: Primary outcomes included self-reported pain (numeric rating scale) and disability (pelvic girdle questionnaire). Secondary outcomes included functional tests (active straight leg raising [ASLR] fatigue, timed up-and-go, and 6-meter walking tests) and muscle contractibility indicated by muscle thickness changes for abdominal muscles and bladder base displacement for PFM (ultrasonographic measures). RESULTS: The BIO+EXE group had lower pain [1.8 (1.5) vs. 4.4 (1.5), mean difference -2.6, 95% confidence interval (CI) -3.9 to -1.2] and disability [14% (10) vs. 28% (21), mean difference -14, 95% CI -25 to -2] and faster walking speed [3.1 seconds (1) vs. 3.3 seconds (1), mean difference -0.2, 95% CI -1.0 to -0.2] than the CON group. The EXE group only had lower pain intensity compared to the CON group [2.7 (2.0) vs. 4.4 (1.5), mean difference -1.7, 95% CI -3.1 to -0.4]. No significant differences were observed among groups in timed up-and-go, ASLR fatigue, or muscle contractibility. CONCLUSIONS: Integrated training for PFM and stabilization with TAUS-guided biofeedback seems to be beneficial for reducing pain and disability in postpartum women with PPGP. CONTRIBUTION OF THE PAPER.

Calycosin Enhances Heat Shock Related-Proteins in H9c2 Cells to Modulate Survival and Apoptosis against Heat Shock.

Heat shock proteins (HSPs), which function as chaperones, are activated in response to various environmental stressors. In addition to their role in diverse aspects of protein production, HSPs protect against harmful protein-related stressors. Calycosin exhibits numerous beneficial properties. This study aims to explore the protective effects of calycosin in the heart under heat shock and determine its underlying mechanism. H9c2 cells, western blot, TUNEL staining, flow cytometry, and immunofluorescence staining were used. The time-dependent effects of heat shock analyzed using western blot revealed increased HSP expression for up to 2[Formula: see text]h, followed by protein degradation after 4[Formula: see text]h. Hence, a heat shock damage duration of 4[Formula: see text]h was chosen for subsequent investigations. Calycosin administered post-heat shock demonstrated dose-dependent recovery of cell viability. Under heat shock conditions, calycosin prevented the apoptosis of H9c2 cells by upregulating HSPs, suppressing p-JNK, enhancing Bcl-2 activation, and inhibiting cleaved caspase 3. Calycosin also inhibited Fas/FasL expression and activated cell survival markers (p-PI3K, p-ERK, p-Akt), indicating their cytoprotective properties through PI3K/Akt activation and JNK inhibition. TUNEL staining and flow cytometry confirmed that calycosin reduced apoptosis. Moreover, calycosin reversed the inhibitory effects of quercetin on HSF1 and Hsp70 expression, illustrating its role in enhancing Hsp70 expression through HSF1 activation during heat shock. Immunofluorescence staining demonstrated HSF1 translocation to the nucleus following calycosin treatment, emphasizing its cytoprotective effects. In conclusion, calycosin exhibits pronounced protective effects against heat shock-induced damages by modulating HSP expression and regulating key signaling pathways to promote cell survival in H9c2 cells.