Two new species of the genus Kingdonella Uvarov, 1933 (Orthoptera, Acridoidea) and the first reported male of Kingdonellaqinghaiensis Zheng, 1990.

Two new species of the genus Kingdonella and the first report of a male K.qinghaiensis Zheng, 1990 are presented. The new species K.gandensis sp. nov. has similar morphological features to K.wardi Uvarov, 1933, but it differs from the latter in having 1) the hind tibia black; 2) the epiproct, in males, with a median groove in the basal 1/2 and in the apical 1/4; 3) the denticles of the male epiproct black; 4) the outside of the hind femur reddish-brown on the basal 1/4 and black on the apical 3/4; and 5) the ventral face of the hind femur black on the outer side. The second new species, K.biruensis sp. nov., is morphologically close to K.pienbaensis Zheng, 1980 but differs from the latter in having 1) the length of the middle segment (12th segment) of antennae 1.2 times longer than its width; 2) the subgenital plate sharp-cornered in males; 3) the ovipositor smooth; 4) the upper half of hind femur outside surface with two black spots; and 5) the ventral face of the hind femur black on its outer side, red on the basal 2/3, and black on the apical 1/3 of its inner side. Finally, we provide a key to all known species of Kingdonella.

Role of water in the formation of low-temperature coal oxidation products: An experimental isotope tracer study.

The interaction between water and coal is of great significance to the study of coal spontaneous combustion (CSC) in humid mine environments. Here, using an isotope tracing method to trace oxygen atoms in water, the role of water in the formation of CO, CO2, product water, and other substances during CSC was quantitatively studied through thermogravimetry coupled with mass spectrometry (TG-MS). In addition, Pearson correlation analysis was used to evaluate the relationships between the amounts of CO and CO2 generated during CSC and the different functional groups. The migration and transformation paths of oxygen atoms in water were analyzed. The results showed that water participated in the CSC reaction to produce CO, CO2, and product water in a dynamic, temperature-dependent process. CO and CO2 were formed through different reaction paths involving reactions between water and aldehyde and carboxyl groups. Further, carboxyl groups were also involved in the reaction with coal to form product water. The results from this study are helpful for understanding the influence of water in each stage of CSC, thereby aiding in its prevention and control.

Transcending antibiotic resistance: The potential of mass Galla chinensis et camelliae Fermentata to Dismantle Helicobacter pylori biofilms and enhance anti-biotic activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Helicobacter pylori (H. pylori) infections are on the rise, presenting a significant global health challenge. Mass Galla chinesis et camelliae Fermentata (Chinese gall leaven, CGL), a traditional Chinese medicinal product made from the fermentation of Rhus chinensis Mill., is frequently employed to address digestive system ailments. Contemporary pharmacological research reveals that CGL exhibits anti-inflammatory, anti-diarrheal, and enzyme-inhibitory activities and holds potential as a treatment for H. pylori infections. However, the precise mechanisms underlying CGL's efficacy against H. pylori remain to be fully elucidated. AIM: The objective of the study is to evaluate CGL's ability to disrupt the H. pylori biofilm and to explore its synergistic potential with antibiotics in targeting the biofilm-efflux pump system, a mechanism implicated in bacterial resistance. METHORDS: The study determined the Minimum Inhibitory Concentration (MIC) of CGL and metronidazole against H. pylori and evaluated their effects on H. pylori biofilms using an in vitro model. Structural changes induced by drug interventions were compared to those in untreated and antibiotic-treated models through scanning electron microscopy and laser confocal microscopy. The accumulation of H33342 dye in planktonic and biofilm H. pylori before and after drug treatment was assessed to evaluate cell viability and biofilm disruption. The study also involved adding experimental drugs to a biofilm H. pylori medium containing D-glucose, measuring glucose concentrations post-intervention using the glucose oxidase method, and calculating changes in glucose uptake. Finally, the relative expression levels of several genes in planktonic and biofilm H. pylori treated with CGL alone or in combination with antibiotics were measured to understand the impact on the biofilm-efflux pump system. RESULTS: Both CGL alone and in combination with metronidazole demonstrated effective disruption of H. pylori biofilms. The combination therapy was particularly effective in reducing the biofilm transfer-enhancing effect of metronidazole and decreasing SpoT expression in the 'SpoT-(p)ppGpp' pathway, especially in biofilms. It showed a greater inhibition of the 'σ54-gluP-sugar uptake' pathway, with significant reductions in rpoN and gluP expression under biofilm conditions compared to CGL or metronidazole alone. The treatment also suppressed H. pylori proliferation and may have altered glucose uptake mechanisms. Moreover, it significantly inhibited the 'hp0939/hp0497/hp0471-RND efflux pump' pathway, with a notable reduction in gene expression compared to the 1/2 MIC metronidazole treatment. CONCLUSION: This study demonstrates that CGL effectively hinders the development of drug resistance in H. pylori by targeting biofilm formation and critical molecular pathways associated with antibiotic resistance. The synergistic effect of combining CGL with metronidazole notably enhances biofilm disruption and inhibits the bacterium's metabolic and reparative mechanisms. Further in vivo studies are needed to confirm these results and to investigate additional mechanisms of CGL's action.

Tetrahedral DNA-linked aptamer-antibody-based sandwich-type electrochemical sensor with Ag@Au core-shell nanoparticles as a signal amplifier for highly sensitive detection of α-fetoprotein.

The conventional electrochemical detection strategy for alpha-fetoprotein (AFP) is limited by the antigen-antibody (Ag-Ab) reactions and suffers from low sensitivity and poor reproducibility due to the inconsistency of Ab-modified electrodes. Herein, we designed and explored a sandwich-type electrochemical sensor for highly sensitive detection of AFP based on aptamer (Apt)-AFP-Ab interaction mode with silver@gold (Ag@Au) core-shell nanoparticles (NPs) as a signal amplifier. AuNPs were electrodeposited onto MXene (Ti3C2TX)-modified glassy carbon electrode (GCE) to get AuNPs/MXene/GCE and further used as the signal amplification substrate. The tetrahedral DNA-linked AFP aptamers were immobilized onto AuNPs/MXene/GCE surface via Au-S bonds and used as the sensing and recognition platform for AFP capturing. Ag@AuNPs with core-shell structures were synthesized, characterized, and bound with Ab as detection elements by catalyzing H2O2 reduction. In the presence of AFP, a stable Apt-AFP-Ab sandwich structure was formed owing to the high affinities of aptamer and Ab toward the target AFP. The catalytic current produced by H2O2 reduction increased linearly with the logarithm of AFP concentration from 5 × 10-4 ng/mL to 1 × 105 ng/mL, accompanied by a low detection limit (1.6 × 10-4 ng/mL). Moreover, the novel sandwich-type electrochemical sensor shows high sensitivity, outstanding selectivity, and promising performance in the analysis of actual samples, displaying a broad application prospect in bioanalysis.

Distant organ metastasis patterns and prognosis of cervical adenocarcinoma: a population-based retrospective study.

Background: Adenocarcinoma is a common histological subtype of cervical cancer, accounting for 10-15% of all cases. The prognosis of cervical adenocarcinoma with distant organ metastases remains unclear. Therefore, our study aimed to investigate the patterns and prognosis of distant organ metastasis in cervical adenocarcinoma. Methods: We obtained data from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2010 to 2019. Cox regression, Kaplan-Meier, and log-rank analyses were conducted. Results: We observed that adenocarcinoma (AC) of the cervix primarily metastasizes to single organs, with a rate of 73.3%. The lungs are the most common organs of metastasis, followed by the liver and bones. Patients with bone metastases have a median survival period of 12 months, which is slightly longer compared to metastasis in other organs. Distant organ metastasis, age, positive lymph nodes, higher AJCC stages, larger tumor diameter, and higher cell grades are related to poor prognosis (p < 0.001). Furthermore, we have observed that surgical intervention, radiotherapy, and chemotherapy can potentially provide benefits for patients with distant organ metastases. Conclusion: Metastasis is an independent prognostic factor for cervical adenocarcinoma patients. Surgery, radiotherapy, and chemotherapy can provide an overall survival advantage for patients with distant organ metastases.

Decoding Fujian's cervical HPV landscape: unmasking dominance of non-16/18 HR-HPV and tailoring prevention strategies at a large scale.

Background: Persistent HR-HPV causes cervical cancer, exhibiting geographic variance. Europe/Americas have higher HPV16/18 rates, while Asia/Africa predominantly have non-16/18 HR-HPV. This study in Fujian, Asia, explores non-16/18 HR-HPV infections, assessing their epidemiology and cervical lesion association for targeted prevention. Methods: A total of 101,621 women undergoing HPV screening at a hospital in Fujian Province from 2013 to 2019 were included. HPV genotyping was performed. A subset of 11,666 HPV-positive women with available histopathology results were analyzed to characterize HPV genotype distribution across cervical diagnoses. Results: In 101,621 samples, 24.5% tested positive for HPV. Among these samples, 17.3% exhibited single infections, while 7.2% showed evidence of multiple infections. The predominant non-16/18 high-risk HPV types identified were HPV 52, 58, 53, 51, and 81. Single HPV infections accounted for 64.1% of all HPV-positive cases, with 71.4% of these being non-16/18 high-risk HPV infections. Age-related variations were observed in 11,666 HPV-positive patients with pathological results. Cancer patients were older. In the cancer group, HPV52 (21.8%) and HPV58 (18.6%) were the predominant types, followed by HPV33, HPV31, and HPV53. Compared to single HPV16/18 infection, non-16/18 HPV predominated in LSIL. Adjusted odds ratios (OR) for LSIL were elevated: multiple HPV16/18 (OR 2.18), multiple non-16/18 HR-HPV (OR 2.53), and multiple LR-HPV (OR 2.38). Notably, solitary HPV16/18 conferred higher odds for HSIL and cancer. Conclusion: Our large-scale analysis in Fujian Province highlights HPV 52, 58, 53, 51, and 81 as predominant non-16/18 HR-HPV types. Multiple HPV poses increased LSIL risks, while solitary HPV16/18 elevates HSIL and cancer odds. These findings stress tailored cervical cancer prevention, highlighting specific HPV impacts on lesion severity and guiding region-specific strategies for optimal screening in Asia, emphasizing ongoing surveillance in the vaccination era.

Cardiovascular disease therapeutics via engineered oral microbiota: Applications and perspective.

Engineering bacteria are considered as a potential treatment for cardiovascular diseases and related risk factors. Oral bacteria are closely related to the occurrence and development of cardiovascular diseases, and their engineering has broad prospects and potential in the treatment of cardiovascular diseases. Oral pathogenic bacteria undergo protein and genetic engineering, including the incorporation of exogenous plasmids to yield therapeutic effects; genetically engineered oral probiotics can be harnessed to secrete cytokines and reactive oxygen species, offering novel therapeutic avenues for cardiovascular diseases.

Highly efficient iron-catalyzed conjugate reduction of α,ß-unsaturated ketones with polymethylhydrosiloxane.

An iron-catalyzed ligand free conjugate reduction of α,ß-unsaturated ketones with PMHS (polymethylhydrosiloxane) was reported to deliver the corresponding carbonyl compounds with up to 93% yield. This operationally simple protocol shows a broad substrate scope using readily available PMHS as a cost-effective and easy-to-handle reductive reagent.

Redox-modulated SNX25 as a novel regulator of GPCR-G protein signaling from endosomes.

GPCR-G protein signaling from endosomes plays a crucial role in various physiological and pathological processes. However, the mechanism by which endosomal G protein signaling is terminated remains largely unknown. In this study, we aimed to investigate the regulatory mechanisms involved in terminating the signaling of Gα subunits from endosomes. Through structural analysis and cell-based assays, we have discovered that SNX25, a protein that targets endosomes via its PXA or PXC domain, interacts with regulator of G protein signaling (RGS) proteins (including RGS2, RGS4, RGS8, and RGS17) in a redox-regulated manner. The interaction between SNX25 and these RGS proteins enhances their GTPase-accelerating activity towards Gαi/q and their ability to bind GDP-bound (inactive form) Gαi/q. As a result, SNX25 recruits these RGS proteins to endosomes, leading to the termination of endosomal Gαi/q signaling. Furthermore, we have found that the SNX25/RGS complex also exerts a negative regulatory effect on Gαi/q signaling from the plasma membrane. This is achieved by recruiting Gαi/q to endosomes and preventing its activation on the plasma membrane. Our findings shed light on the previously unknown role of redox-modulated SNX25 in inhibiting Gαi/q signaling, thereby uncovering a novel mechanism for terminating Gαi/q signaling from endosomes. Importantly, this study expands our understanding of the regulation of GPCR-Gαi/q signaling beyond the plasma membrane.

A novel distributed meta-module motion design for modular robotic systems based on grid partition method.

This article studies a meta-module motion design approach for homogenous modular robotic systems in self-configuration. By utilizing configuration diversity, scalability and unit-substitutability, homogenous modular robotic systems can be a promising approach to life detection and space exploration in the future. Based on the requirements of the potential applications, self-configuration can be considered as the precondition. As similar to swarm robotic systems, the distributed control strategy in which the modular robots are operated in a sequence of motion circles consist of 'detection'- 'decision'- 'execution' is of great significance. However, there is a limitation to the applicability of previously proposed work on the self-configuration topic, due to the fact that the self-configuration strategy execution suffers from the motion constraints of modular robots. In order to solve the problem, we propose a grid partition method that removes the gap between the locomotion of a single modular robot and the reconfiguration of the whole system. Under the analysis of the grid partition, the meta-module motion design is proposed to realize the distributed self-configuration strategy. We simulated the self-configuration in M-Lattice, a two-dimensional homogenous modular robotic system.

Gut microorganisms of Locusta migratoria in various life stages and its possible influence on cellulose digestibility.

Locusta migratoria is an important phytophagous pest, and its gut microbial communities play an important role in cellulose degradation. In this study, the gut microbial and cellulose digestibility dynamics of Locusta migratoria were jointly analyzed using high-throughput sequencing and anthrone colorimetry. The results showed that the gut microbial diversity and cellulose digestibility across life stages were dynamically changing. The species richness of gut bacteria was significantly higher in eggs than in larvae and imago, the species richness and cellulose digestibility of gut bacteria were significantly higher in early larvae (first and second instars) than in late larvae (third to fifth instars), and the diversity of gut bacteria and cellulose digestibility were significantly higher in imago than in late larvae. There is a correlation between the dynamics of gut bacterial communities and cellulose digestibility. Enterobacter, Lactococcus, and Pseudomonas are the most abundant genera throughout all life stages. Six strains of highly efficient cellulolytic bacteria were screened, which were dominant gut bacteria. Carboxymethyl cellulase activity (CMCA) and filter paper activity (FPA) experiments revealed that Pseudomonas had the highest cellulase enzyme activity. This study provides a new way for the screening of cellulolytic bacteria and lays the foundation for developing insects with significant biomass into cellulose-degrading bioreactors. IMPORTANCE: Cellulose is the most abundant and cheapest renewable resource in nature, but its degradation is difficult, so finding efficient cellulose degradation methods is an urgent challenge. Locusta migratoria is a large group of agricultural pests, and the large number of microorganisms that inhabit their intestinal tracts play an important role in cellulose degradation. We analyzed the dynamics of Locusta migratoria gut microbial communities and cellulose digestibility using a combination of high-throughput sequencing technology and anthrone colorimetry. The results revealed that the gut microbial diversity and cellulose digestibility were dynamically changed at different life stages. In addition, we explored the intestinal bacterial community of Locusta migratoria across life stages and its correlation with cellulose digestibility. The dominant bacterial genera at different life stages of Locusta migratoria were uncovered and their carboxymethyl cellulase activity (CMCA) and filter paper activity (FPA) were determined. This study provides a new avenue for screening cellulolytic bacteria and lays the foundation for developing insects with significant biomass into cellulose-degrading bioreactors.

Material Engineering Strategies for Efficient Hydrogen Evolution Reaction Catalysts.

Water electrolysis, a key enabler of hydrogen energy production, presents significant potential as a strategy for achieving net-zero emissions. However, the widespread deployment of water electrolysis is currently limited by the high-cost and scarce noble metal electrocatalysts in hydrogen evolution reaction (HER). Given this challenge, design and synthesis of cost-effective and high-performance alternative catalysts have become a research focus, which necessitates insightful understandings of HER fundamentals and material engineering strategies. Distinct from typical reviews that concentrate only on the summary of recent catalyst materials, this review article shifts focus to material engineering strategies for developing efficient HER catalysts. In-depth analysis of key material design approaches for HER catalysts, such as doping, vacancy defect creation, phase engineering, and metal-support engineering, are illustrated along with typical research cases. A special emphasis is placed on designing noble metal-free catalysts with a brief discussion on recent advancements in electrocatalytic water-splitting technology. The article also delves into important descriptors, reliable evaluation parameters and characterization techniques, aiming to link the fundamental mechanisms of HER with its catalytic performance. In conclusion, it explores future trends in HER catalysts by integrating theoretical, experimental and industrial perspectives, while acknowledging the challenges that remain.

The abnormalities of lipid metabolism in children and adolescents with major depressive disorder and relationship with suicidal ideation and attempted suicide.

Background: Major depressive disorder (MDD) is a widespread health issue in many countries, which has an extremely negative impact on the health of children and adolescents in particular. In the context of depression and metabolic disorders, dyslipidemia and metabolism-related problems become more prominent comorbidities. However, they continue to be the main barrier to the successful recovery of the clinical progress. In this study we investigated the rate of dyslipidemia, additional risk factors among Chinese children and adolescents with MDD, and association of the suicidal behavior with lipid levels. Methods: The study took 756 people from the Third People's Hospital of Fuyang between January 2020 and December 2021, aged between 8 and 18, with major depressive disorders diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). We determined the FBG (fasting blood glucose) and lipid parameters in all subjects and also investigated the history of suicidal ideation, the cases of attempted suicide, and the scores of depressive symptoms. Sociodemographic and clinical data were gathered and analyzed using the SPSS-23.0 version. Results: The prevalence of hypercholesterolemia, hypertriglyceridemia, high LDL-C, and low HDL-C were 5.42 % (41/756), 10.58 % (80/756), 3.84 % (29/756) and 5.42 % (41/756) respectively. For hypercholesterolemia and hypertriglyceridemia, they were positive associated with suicidal ideation and suicide attempts, and the positive correlation is shown between low HDL-C levels and suicide attempts. Nevertheless, non-ideation and inversely suicidal attempts were not discovered among high-LDL-C subjects. Logistic analysis showed that high levels of FBG (OR = 2.86, 95 % CI: 1.31-6.25, P = 0.008) and worse LDL-C (OR = 357.82, 95 % CI: 66.16-1935.10, P < 0.001) are the independent associated factors for hypercholesterolemia. More hospitalizations (OR = 1.89, 95 % CI: 1.07-3.35, P = 0.028), obesity (OR = 2.55, 95 % CI: 1.25-5.18, P = 0.010), high levels of TC (OR = 2.15, 95 % CI: 1.03-4.48, P = 0.042), and higher doses of antidepressants (OR = 1.02, 95 % CI: 1.00-1.04, P = 0.029) were independently associated factors for hypertriglyceridemia, while high levels of HDL-C (OR = 0.11, 95 % CI: 0.04-0.31, P < 0.001) were protective factors. In addition, high levels of TC (OR = 113.94, 95 % CI: 20.01-648.85) were statistically different (P < 0.001) and suggested that the factor was significantly related to high LDL-C. Meanwhile, older age (OR = 1.25, 95 % CI: 1.02-1.52, P = 0.030) and high levels of TG (OR = 3.00, 95 % CI: 1.98-4.55, P < 0.001) were independent factors contributing to low HDL-C. Conclusion: The high prevalence of dyslipidemia in childhood and adolescence among children and adolescents with depressive disorder has become a public health issue. Hypercholesterolemia and hypertriglyceridemia showed a positive correlation with suicidal thoughts and suicidal attempts. Monitoring the incidence of suicidal thoughts and attempts among them would carry some predictor meaning in therapy and for jumping back to health.

Adsorption of Cadmium and Lead Capacity and Environmental Stability of Magnesium-Modified High-Sulfur Hydrochar: Greenly Utilizing Chicken Feather.

Chicken feathers represent a viable material for producing biochar adsorbents. Traditional slow pyrolysis methods often result in sulfur element losses from chicken feathers, whereas hydrothermal reactions generate substantial amounts of nutrient-rich hydrothermal liquor. Magnesium-modified high-sulfur hydrochar MWF was synthesized through magnesium modification, achieving a S content of 3.68%. The maximum equilibrium adsorption amounts of MWF for Cd2+ and Pb2+ were 25.12 mg·g-1 and 70.41 mg·g-1, respectively, representing 4.00 times and 2.75 times of WF. Magnesium modification elevated the sulfur content, pH, ash content, and electronegativity of MWF. The primary mechanisms behind MWF's adsorption of Cd2+ and Pb2+ involve magnesium ion exchange and complexation with C=O/O=C-O, quaternary N, and S functional groups. MWF maintains robust stability and antioxidative properties, even with low aromaticity levels. Given the lower energy consumption during hydrochar production, MWF offers notable carbon sequestration benefits. The hydrothermal solution derived from MWF is nutrient-rich. Following supplementation with inorganic fertilizer, the hydrothermal solution of MWF significantly enhanced bok choy growth compared to the control group. In general, adopting magnesium-modified hydrothermal reactions to produce hydrochar and converting the resultant hydrothermal solution into water-soluble fertilizer proves a viable strategy for the eco-friendly utilization of chicken feathers. This approach carries substantial value for heavy metal remediation and agricultural practices.

Two new species of Striglina Guenée, 1877 (Lepidoptera, Thyrididae) from China.

Background: The genus Striglina is the most species-rich genus in the subfamily Striglininae, which includes about 80 species and subspecies and it has always been a popular research taxon within Thyrididae. New information: Two new species of the genus Striglina Guenée, 1877, S.whalleyi sp. nov. and S.pararubricans sp. nov. from China are described and illustrated. Striglinawhalleyi sp. nov. is similar to S.irresectaobscura Whalley, 1976, but its wing ground colour is lighter and the sacculus process is shorter. Striglinapararubricans sp. nov. is similar to S.rubricans, but the fore-wing is narrower, the uncus processes and sacculus process are longer. Holotypes are deposited in the Department of Entomology, College of Plant Protection, South China Agricultural University, Guangzhou.

Loop PDE of viral capsid protein is involved in immune escape of the emerging novel variant infectious bursal disease virus.

Infectious bursa disease (IBD) is an acute, highly contactable, lethal, immunosuppressive infectious disease caused by the Infectious bursa disease virus (IBDV). Currently, the emerged novel variant IBDV (nVarIBDV) and the sustainedly prevalent very virulent IBDV (vvIBDV) are the two most prevalent strains of IBDV in China. The antigenic properties of the two prevalent strains differed significantly, which led to the escape of nVarIBDV from the immune protection provided by the existing vvIBDV vaccine. However, the molecular basis of the nVarIBDV immune escape remains unclear. In this study, we demonstrated, for the first time, that residues 252, 254, and 256 in the PDE of VP2 are involved in the immune escape of the emerging nVarIBDV. Firstly, the IFA-mediated antigen-antibody affinity assay showed that PBC and PDE of VP2 could affect the affinity of vvIBDV antiserum to VP2, of which PDE was more significant. The key amino acids of PDE influencing the antigen-antibody affinity were also identified, with G254N being the most significant, followed by V252I and I256V. Then the mutated virus with point or combined mutations was rescued by reverse genetics. it was further demonstrated that mutations of V252I, G254N, and I256V in PDE could individually or collaboratively reduce antigen-antibody affinity and interfere with antiserum neutralization, with G254N being the most significant. This study revealed the reasons for the widespread prevalence of nVarIBDV in immunized chicken flocks and provided innovative ideas for designing novel vaccines that match the antigen of the epidemic strain.

In utero and postnatal ivacaftor/lumacaftor therapy rescues multiorgan disease in CFTR-F508del ferrets.

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, with F508del being the most prevalent mutation. The combination of CFTR modulators (potentiator and correctors) has provided benefit to CF patients carrying the F508del mutation; however, the safety and effectiveness of in utero combination modulator therapy remains unclear. We created a F508del ferret model to test whether ivacaftor/lumacaftor (VX-770/VX-809) therapy can rescue in utero and postnatal pathologies associated with CF. Using primary intestinal organoids and air-liquid interface cultures of airway epithelia, we demonstrate that the F508del mutation in ferret CFTR results in a severe folding and trafficking defect, which can be partially restored by treatment with CFTR modulators. In utero treatment of pregnant jills with ivacaftor/lumacaftor prevented meconium ileus at birth in F508del kits and sustained postnatal treatment of CF offspring improved survival and partially protected from pancreatic insufficiency. Withdrawal of ivacaftor/lumacaftor treatment from juvenile CF ferrets reestablished pancreatic and lung diseases, with altered pulmonary mechanics. These findings suggest that in utero intervention with a combination of CFTR modulators may provide therapeutic benefits to individuals with F508del. This CFTR-F508del ferret model may be useful for testing therapies using clinically translatable endpoints.

Deciphering the role of wound healing genes in skin cutaneous melanoma: Insights into expression, methylation, mutations, and therapeutic implications.

Skin Cutaneous Melanoma (SKCM) is a form of cancer that originates in the pigment-producing cells, known as melanocytes, of the skin. Delay wound healing is often correlated with the occurrence of and progression of SKCM. In this comprehensive study, we investigated the intricate roles of two important wound healing genes in SKCM, including Matrix Metalloproteinase-2 (MMP2) and Matrix Metalloproteinase-9 (MMP9). Through a multi-faceted approach, we collected clinical samples, conducted molecular experiments, including RT-qPCR, bisulphite sequencing, cell culture, cell Counting Kit-8, colony formation, and wound healing assays. Beside this, we also used various other databases/tools/approaches for additional analysis including, UALCAN, GEPIA, HPA, MEXPRESS, cBioPortal, KM plotter, DrugBank, and molecular docking. Our results revealed a significant up-regulation of MMP2 and MMP9 in SKCM tissues compared to normal counterparts. Moreover, promoter methylation analysis suggested an epigenetic regulatory mechanism. Validations using TCGA datasets and immunohistochemistry emphasized the clinical relevance of MMP2 and MMP9 dysregulation. Functional assays demonstrated their synergistic impact on proliferation and migration in SKCM cells. Furthermore, we identified potential therapeutic candidates, Estradiol and Calcitriol, through drug prediction and molecular docking analyses. These compounds exhibited binding affinities, suggesting their potential as MMP2/MMP9 inhibitors. Overall, our study elucidates the diagnostic, prognostic, and therapeutic implications of MMP2 and MMP9 in SKCM, shedding light on their complex interplay in SKCM occurrence and progression.

Recent advances in photothermal nanomaterials-mediated detection of circulating tumor cells.

Photothermal materials have shown great potential for cancer detection and treatment due to their excellent photothermal effects. Circulating tumor cells (CTCs) are tumor cells that are shed from the primary tumor into the blood and metastasize. In contrast to other tumor markers that are free in the blood, CTCs are a collective term for all types of tumor cells present in the peripheral blood, a source of tumor metastasis, and clear evidence of tumor presence. CTCs detection enables early detection, diagnosis and treatment of tumors, and plays an important role in cancer prevention and treatment. This review summarizes the application of various photothermal materials in CTC detection, including gold, carbon, molybdenum, phosphorus, etc. and describes the significance of CTC detection for early tumor diagnosis and tumor prognosis. Focus is also put on how various photothermal materials play their roles in CTCs detection, including CT, imaging and photoacoustic and therapeutic roles. The physicochemical properties, shapes, and photothermal properties of various photothermal materials are discussed to improve the detection sensitivity and efficiency and to reduce the damage to normal cells. These photothermal materials are capable of converting radiant light energy into thermal energy for highly-sensitive CTCs detection and improving their photothermal properties by various methods, and have achieved good results in various experiments. The use of photothermal materials for CTCs detection is becoming more and more widespread and can be of significant help in early cancer screening and later treatment.