Metformin modifies plasma microbial-derived extracellular vesicles in polycystic ovary syndrome with insulin resistance.

INTRODUCTION: This study investigated changes in plasma microbial-derived extracellular vesicles (EVs) in patients with polycystic ovary syndrome and insulin resistance (PCOS-IR) before and after metformin treatment, and aimed to identify bacterial taxa within EVs that were biologically and statistically significant for diagnosis and treatment. METHODS: The case-control study was conducted at Xiamen Chang Gung Hospital, Hua Qiao University. Plasma samples were collected from five PCOS-IR patients of childbearing age before and after 3 months of metformin treatment, and the samples were sequenced. The diversity and taxonomic composition of different microbial communities were analyzed through full-length 16 S glycosomal RNA gene sequencing. RESULTS: After metformin treatment, fasting plasma glucose levels and IR degree of PCOS-IR patients were significantly improved. The 16 S analysis of plasma EVs from metformin-treated patients showed higher microbial diversity. There were significant differences in EVs derived from some environmental bacteria before and after metformin treatment. Notably, Streptococcus salivarius was more abundant in the metformin-treated group, suggesting it may be a potential probiotic. DISCUSSION: The study demonstrated changes in the microbial composition of plasma EVs before and after metformin treatment. The findings may offer new insights into the pathogenesis of PCOS-IR and provide new avenues for research.

Making the Complicated Simple: A Minimizing Carrier Strategy on Innovative Nanopesticides.

The flourishing progress in nanotechnology offers boundless opportunities for agriculture, particularly in the realm of nanopesticides research and development. However, concerns have been raised regarding the human and environmental safety issues stemming from the unrestrained use of non-therapeutic nanomaterials in nanopesticides. It is also important to consider whether the current development strategy of nanopesticides based on nanocarriers can strike a balance between investment and return, and if the complex material composition genuinely improves the efficiency, safety, and circularity of nanopesticides. Herein, we introduced the concept of nanopesticides with minimizing carriers (NMC) prepared through prodrug design and molecular self-assembly emerging as practical tools to address the current limitations, and compared it with nanopesticides employing non-therapeutic nanomaterials as carriers (NNC). We further summarized the current development strategy of NMC and examined potential challenges in its preparation, performance, and production. Overall, we asserted that the development of NMC systems can serve as the innovative driving force catalyzing a green and efficient revolution in nanopesticides, offering a way out of the current predicament.

Isolation, purification, and biological activities of polysaccharides from Amorpha fruticosa flowers.

The extraction, isolation, structural characterisation and biological activities of polysaccharides from Amorpha fruticosa flowers were investigated. First, the crude polysaccharide AFP was extracted, and two major purified polysaccharide fractions AFP-2 and AFP-3 were isolated. The molecular weight and monosaccharide compositions of AFP-2 and AFP-3 were determined. Then the antioxidant activities of AFP, AFP-2 and AFP-3 were assessed by DPPH radical, ß-Carotene bleaching and hydroxyl radical assays. All three tested polysaccharides showed good antioxidant activity while AFP was the strongest one. The study also showed that AFP, AFP-2 and AFP-3 have good tyrosinase inhibition, moisture absorption and retention activities. The results will provide a helpful reference for the application of polysaccharide from Amorpha fruticosa flowers as a natural cosmetic ingredient.

A perovskite-based electrochemiluminescence aptasensor for tetracycline screening.

Tetracyclines are currently the most commonly used class of antibiotics, and their residue issue significantly impacts public health safety. In this study, a surface modification of perovskite with cetyltrimethylammonium bromide led to the generation of stable electrochemiluminescence (ECL) emitters in aqueous systems and improved the biocompatibility of perovskite. A perovskite quantum dot-based ECL sensing strategy was developed. Utilizing the corresponding aptamer of the antibiotics, strain displacement reactions were triggered, disrupting the ECL quenching system composed of perovskite and Ag nanoclusters (Ag NCs) on the electrode surface, generating a signal to achieve quantitative detection of several common tetracycline antibiotics. The perovskite quantum dot provided a strong and stable initial signal, while the efficient catalytic activity of the silver cluster enhanced the recognition sensitivity. Tetracycline, chlortetracycline, and oxytetracycline were used as examples to demonstrate the differentiation and quantitative detection through this method. In addition, the aptasensor exhibited analytical performance with the linear range (0.1-10 µM OTC) and good recovery rates of 94.7% to 101.6% in real samples. This approach has the potential to become a sensitive and practical approach for assessing antibiotic residues.

Compound four-cavity single-longitudinal mode fiber laser.

A compound resonant cavity-type single longitudinal mode erbium-doped fiber laser is proposed and verified in this paper. We use a compound four-cavity to expand the longitudinal mode spacing of the laser and a homemade grating F-P filter and a saturable absorber to narrow the gain spectral bandwidth, enabling the laser to operate in a single-frequency state. Through theoretical analysis and experimental verification of the important roles of the main constructed fiber laser parts, the center wavelength of the laser output of 1550.06 nm is obtained, and the optical signal-to-noise ratio is 65 dB. In a 50 minute period, the wavelength fluctuation is exhibited along with the maximum power fluctuation of 0.28 dB. The value of the laser output linewidth is ∼250 Hz, measured by using the delayed self-heterodyne method.

EZH2/G9a interact to mediate drug resistance in non-small-cell lung cancer by regulating the SMAD4/ERK/c-Myc signaling axis.

Drug resistance is the leading problem in non-small-cell lung cancer (NSCLC) therapy. The contribution of histone methylation in mediating malignant phenotypes of NSCLC is well known. However, the role of histone methylation in NSCLC drug-resistance mechanisms remains unclear. Here, our data show that EZH2 and G9a, two histone methyltransferases, are involved in the drug resistance of NSCLC. Gene manipulation results indicate that the combination of EZH2 and G9a promotes tumor growth and mediates drug resistance in a complementary manner. Importantly, clinical study demonstrates that co-expression of both enzymes predicts a poor outcome in patients with NSCLC. Mechanistically, G9a and EZH2 interact and promote the silencing of the tumor-suppressor gene SMAD4, activating the ERK/c-Myc signaling pathway. Finally, SU08, a compound targeting both EZH2 and G9a, is demonstrated to sensitize resistant cells to therapeutic drugs by regulating the SMAD4/ERK/c-Myc signaling axis. These findings uncover the resistance mechanism and a strategy for reversing NSCLC drug resistance.

Nano-Micro Core-Shell Fibers for Efficient Pest Trapping.

Insect sex pheromones as an alternative to chemical pesticides hold promising prospects in pest control. However, their burst release and duration need to be optimized. Herein, pheromone-loaded core-shell fibers composed of degradable polycaprolactone and polyhydroxybutyrate were prepared by coaxial electrospinning. The results showed that this core-shell fiber had good hydrophobic performance and thermal stability, and the light transmittance in the ultraviolet band was only below 40%, which provided protection to pheromones. The core-shell structure alleviated the burst release of pheromone in the fiber and extended the release time to about 133 days. In the field, the pheromone-loaded core-shell fibers showed the same continuous and efficient trapping of Spodoptera litura as the commercial carriers. More importantly, the electrospun fibers combined with biomaterials had a degradability unmatched by commercial carriers. The structure design strategy provides ideas for the innovative design of pheromone carriers and is a potential tool for the management of agricultural pests.

Characterisation and skin protection activities of polysaccharides from Schnabelia terniflora.

The bioactivities of crude polysaccharides from leaves (L-Ps) and flowers (F-Ps) of Schnabelia terniflora (Maxim.) P. D. Cantino were studied, and the characteristics of purified fractions were analysed by HPLC, HP-GPC and NMR. L-Ps exhibited strong DPPH radical scavenging activity (IC50 value of 251.53 ± 4.62 µg/mL) and tyrosinase inhibition (IC50 value of 163.52 ± 2.59 µg/mL). However, the maximum moisture absorption (74.67 ± 1.53%) and retention (68.00 ± 3.61%) abilities were observed in F-Ps. Two main fractions separated by DEAE-Sepharose fast flow column from L-Ps were eluted with 0.1 and 0.3 M NaCl, while one main fraction from F-Ps was eluted with 0.1 M NaCl. Purified fractions were obviously different in monosaccharide composition, molecular weight and 1H NMR and 13C NMR spectra. Therefore, the current manuscript can provide an important evidence for the potential development of L-Ps and F-Ps as promising ingredients in cosmetics industry.

The dyadic relationship of supportive care needs with quality of life in lung cancer survivor and spousal caregiver couples.

Objective: This study aimed to explore the dyadic interrelationships between supportive care needs (SCNs) and quality of life (QOL) among lung cancer (LC) survivors and their spousal caregivers. Methods: In this cross-sectional study, 443 dyads were recruited from three tertiary hospitals in two cities (Fuzhou and Putian) in Fujian Province, China, between May 2020 and May 2021. The study shows that participants completed a sociodemographic information sheet, the SCNs survey, and answered the Chinese version of the World Health Organization Quality of Life-BREF questionnaire by telephone. The data were analyzed using descriptive statistics and Pearson's correlations. This study used the actor-partner interdependence model (APIM) with dyad analysis to examine the effect of LC survivors and spouses unmet SCNs on QOL. Results: LC survivor's and spouse's QOL levels were influenced by the level of unmet SCNs (the actor effect). LC survivors unmet SCNs were significantly negatively associated with their spouse's QOL (the partner effect). There were no partner effects between the spouse's unmet SCNs and the LC survivor's QOL. The APIM model produced an acceptable model fit [χ2/df = 2.84 (147), comparative fit index (CFI) = 0.94, Tucker-Lewis index (TLI) = 0.93, root mean square error of approximation (RMSEA) = 0.07]. Conclusions: The level of unmet SCNs significantly affected QOL in survivor and spouse dyads. Although partner effects were weaker than actor effects, healthcare providers should develop tailored LC dyadic self- and family-management interventions to provide SCN-driven care to LC survivors and their spouses.

Multifunctional Borax Cross-Linked Hydroxypropyl Guar Gum Hydrogels with Crop Nutritional Function as Carriers for Dual-Responsive Acaricide Release.

Hydrogels with porous networks have received considerable attention in smart pesticide delivery due to their inherent versatility. In this study, acaricide cyetpyrafen (CPF)-loaded borax (BO) cross-linked hydroxypropyl guar gum (HPG) (CPF@BO-co-HPG, CBG) hydrogels were prepared by cross-linking and pesticide loading simultaneously. The flowable CBG hydrogels with 3D porous network structures had better wetting and spreading ability on Citrus reticulata Blanco leaves and a hydrophobic interface. The nonflowable CBG hydrogels had pH- and temperature-responsive release properties. Meanwhile, the acaricidal efficacy of CBG against Panonychus citri (McGregor) at both 24 and 48 h was significantly higher than those of CPF-loaded BO-free HPG hydrogels. Furthermore, CBG had a nutritional function for cotton growth and environmental safety for zebrafish. This research developed a BO cross-linked HPG hydrogel as a smart pesticide delivery vehicle and crop nutrient replenishment, which can be widely applied in sustainable agriculture.

Ginkgolide B promotes spontaneous recovery and enhances endogenous netrin-1 after neonatal hypoxic-ischemic brain damage.

OBJECTIVES: Perinatal hypoxic-ischemic encephalopathy (HIE) is a condition that can lead to long-term cognitive, motor, and behavioral impairments in newborns. Although brain hypothermia therapy is currently the standard treatment for HIE, it does not provide complete neuroprotection. As a result, there is a need to explore additional therapies to enhance treatment outcomes. This study aims to investigate the potential role of Ginkgolide B (GB) in promoting neuroplasticity and facilitating spontaneous recovery after HIE. METHODS: In this study, we employed a neonatal rat model of HIE to investigate the effects of GB on spontaneous recovery. GB treatment was initiated 24 h after hypoxia and administered continuously for a duration of 14 days. We evaluated several outcome measures after the treatment period, including spontaneous behavioral recovery and brain repair. Additionally, we quantified the levels of netrin-1 in both plasma and the peri-ischemic zone after the occurrence of HIE. RESULTS: We found that GB treatment significantly facilitated spontaneous behavioral recovery in the HIE pups. Furthermore, cognitive function was restored, and brain tissue repair had a noticeable acceleration. We observed increased cell proliferation in the subventricular, stratum, and subgranular zones. Of particular interest, we observed elevated levels of netrin-1 in both plasma and the ischemic penumbra following GB treatment. CONCLUSION: Our findings suggest that GB promotes neuroplasticity and enhances spontaneous recovery in newborns affected by HIE. The observed upregulation of netrin-1 may be crucial in mediating these effects. These results highlight the promising potential of GB as a post-HIE therapy, particularly in enhancing spontaneous recovery and improving long-term outcomes.

Epinodosin suppresses the proliferation, invasion, and migration of esophageal squamous cell carcinoma by mediating miRNA-143-3p/Bcl-2 axis.

Epinodosin has shown antibacterial and antitumor biological characteristics in the documents. We found that Epinodosin has an effective inhibitory effect on esophageal squamous cell carcinoma (ESCC). However, the potential roles and mechanisms of Epinodosin in ESCC remain unclear. We performed many experiments to clarify the effect and mechanism of Epinodosin on ESCC. In this study, cell viability, invasion, migration, and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,-diphenytetrazoliumromide (MTT), Transwell, and flow cytometry. The differentially expressed miRNAs were screened through RNA transcriptome sequencing. The expression levels of miRNA-143-3p and some proteins were measured by real-time polymerase chain reaction (PCR) and Western blot. The anticancer effects of Epinodosin in vivo were determined by a nude mouse model. Epinodosin suppressed cell proliferation/invasion/migration and induced ESCC cell apoptosis. Epinodosin remarkably affected the protein expression of mitogen-activated protein kinase (MAPK) signaling pathway. The animal experiments demonstrated that Epinodosin could attenuate the growth of ESCC tumors in nude mice. The expression of p53, Bim, and Bax was upregulated, while that of Bcl-2 was downregulated in tumor tissues. In conclusion, Epinodosin suppresses cell viability/invasion/migration, while induces ESCC cell apoptosis by mediating miRNA-143-3p and Bcl-2, and can markedly attenuate the growth of ESCC tumors in nude mice.

Biodegradable electrospun fibers as sustained-release carriers of insect pheromones for field trapping of Spodoptera litura (Lepidoptera: Noctuidae).

BACKGROUND: Insect pheromones are highly effective and environmentally friendly, and are widely used in the monitoring and trapping of pests. However, many researchers have found that various factors such as ultraviolet light and temperature in the field environment can accelerate the volatilization of pheromones, thus affecting the actual control effect. In recent years, electrospinning technology has demonstrated remarkable potential in the preparation of sustained carriers. Moreover, the utilization of biodegradable materials in electrospinning presents a promising avenue for the advancement of eco-friendly carriers. RESULTS: In this study, homogeneous and defect-free pheromone carriers were obtained by electrospinning using fully biodegradable polyhydroxybutyrate materials and pheromones of Spodoptera litura. The electrospun fibers with porous structure could continuously release pheromone (the longest can be ≤80 days). They also had low light transmission, hydrophobic protection. More importantly, the pheromone-loaded electrospun fiber carriers showed stable release and good trapping effect in the field. They could trap pests for at least 7 weeks in the field environment without other light stabilizers added. CONCLUSION: Sustained-release carriers constructed by electrospinning and green materials could improve the efficacy of pheromones and ensure environmental friendliness, and provided a tool for the management of S. litura and other pests and sustainable development of agricultural. © 2023 Society of Chemical Industry.

Autochthonous DOM had solar disinfection effect but nitrate counteracted with them.

Pathogens in natural water can pose great threat to public health and challenge water quality. In sunlit surface water, dissolved organic matters (DOMs) can inactivate pathogens due to their photochemical activity. However, the photoreactivity of autochthonous DOM derived from different source and their interaction with nitrate on photo-inactivation remained limited understood. In this study, the composition and photoreactivity of DOM extracted from Microcystis (ADOM), submerged aquatic plant (PDOM) and river water (RDOM) were studied. Results revealed that lignin and tannin-like polyphenols and polymeric aromatic compounds negatively correlated with quantum yield of 3DOM*, whilst lignin like molecules positively correlated with •OH generation. ADOM had highest photoinactivation efficiency of E. coli, followed by RDOM and PDOM. Both the photogenerated •OH and low energy 3DOM* could inactivate bacteria damaging cell membrane and causing increase of intracellular reactive species. PDOM with more phenolic or polyphenols compounds not only weaken its photoreactivity, also increase regrowth potential of bacteria after photodisinfection. The presence of nitrate counteracted with autochthonous DOMs on photogeneration of •OH and photodisinfection activity, as well as increased the reactivation rate of PDOM and ADOM, which might be attributed to the increase of survival bacteria and more bioavailable fractions provided in systems.

Identification of a novel adjuvant loperamide that enhances the antibacterial activity of colistin against MCR-1-positive pathogens in vitro/vivo.

Severe infection with multidrug-resistant Enterobacterales caused by the plasmid-induced colistin resistance gene MCR-1 is a serious public health challenge. In this case, it is necessary and pressing to find a treatment to overcome antibiotic resistance. Here, we investigated the synergistic effect and mechanism of loperamide combined with colistin against MCR-1-positive pathogens. We evaluated the combined effect of loperamide and colistin using the checkerboard method and the time-kill experiment. The results showed that loperamide could enhance the bactericidal ability of colistin, and this combination regimen could completely kill the tested bacteria within 4 h. Subsequently, spectrofluorimetric methods were used to explore the mechanism of loperamide combined with colistin. The results indicated that the mode of action of loperamide combined with colistin was found to involve mechanical disruption of the membrane. Furthermore, molecular simulation and microscale thermophoresis results revealed that loperamide reduced the impact of MCR-1 protein by directly binding to its active site. In addition, the combined regimen of loperamide and colistin effectively reduced the bacterial load in the thighs of mice while increasing the protection rate by 70%. In short, as a potential lead compound, loperamide can enhance the killing effect of colistin on pathogenic Enterobacterales carrying MCR-1 by causing membrane damage and inhibiting MCR-1 protein activity.

Biphasic alcoholysis coupled with high-speed countercurrent chromatography for high performance on separating phorbol from Croton tiglium Linn extracts.

Phorbol is a tetracyclic diterpenoid found in Euphorbia tirucalli, Croton tiglium, and Rehmannia glutinosa, and is nuclear of various phorbol esters. The rapid obtaining of phorbol with high purity highly contributes to its application, such as synthesizing phorbol esters with designable side chains and particular therapeutic efficacy. This study introduced a biphasic alcoholysis method for obtaining phorbol from croton oil by using polarity imparity organic solvents in both phases and established a high-speed countercurrent chromatography method for simultaneous separation and purification of phorbol. The optimized operation conditions of biphasic alcoholysis were a reaction time of 91 min, a temperature of 14°C, and a croton oil-methanol ratio of 1:30 (g:ml). The phorbol during the biphasic alcoholysis was 3.2-fold higher in content than that obtained in conventional monophasic alcoholysis. The optimized high-speed countercurrent chromatography method was using the ethyl acetate/n-butyl alcohol/water at 4.7:0.3:5 (v:v:v) with Na2 SO4 at 0.36 g/10 ml as the solvent system, using the mobile phase flow rate of 2 ml/min, the revolution of 800 r/min, under which the retention of the stationary phase was achieved at 72.83%. The crystallized phorbol following high-speed countercurrent chromatography was obtained as high purity of 94%.

CD8+ T cell-Dependent Remodeling of the Tumor Microenvironment Overcomes Chemoresistance.

The therapeutic efficacy of chemotherapy is in part a result of its ability to enhance adaptive antitumor immune responses. However, tumor cells exploit various evasion mechanisms to escape the immune attack and blunt chemosensitivity. Herein, we report that through single-cell profiling of the tumor immune microenvironment, we identified a subset of CD161-overexpressing CD8+ T cells enriched in chemoresistant tumors. CD161 engagement repressed the calcium influx and cytolytic capacity of CD8+ T cells through acid sphingomyelinase activation and ceramide generation. Targeting CD161 in adoptively transferred cytotoxic T lymphocytes enhanced antitumor immunity and reversed chemoresistance in patient-derived xenografts in vivo. Clinically, CD161 expression on CD8+ T cells was associated with chemoresistance and shortened patient survival. Our findings provide insights into novel immunosuppressive mechanisms in chemoresistance and highlight targeting CD161 as a potential therapeutic strategy.

CCL18 signaling from tumor-associated macrophages activates fibroblasts to adopt a chemoresistance-inducing phenotype.

The heterogeneity of cancer-associated fibroblasts (CAFs) might be ascribed to differences in origin. CD10 and GPR77 have been reported to identify a chemoresistance-inducing CAF subset in breast cancer. However, the precise mechanism for the formation of the CD10+GPR77+ CAFs remains unknown. In this study, we found that CCL18 expression was positively correlated with the density of CD10+GPR77+ CAFs in breast cancer and associated with a poor response to chemotherapy. Moreover, CCL18 secreted by tumor-associated macrophages (TAMs) activated a CD10+GPR77+ CAF phenotype in normal breast-resident fibroblasts (NBFs), which could then enrich cancer stem cells (CSCs) and induce chemoresistance in breast cancer cells. Mechanistically, CCL18 activated NF-κB signaling via PITPNM3 and thus enhanced the production of IL-6 and IL-8. Furthermore, intratumoral CCL18 injection significantly induced the activation of NBFs and the chemoresistance of xenografts in vivo. In addition, targeting CCL18 by anti-CCL18 antibody could inhibit the formation of CD10+GPR77+ CAFs and recover the chemosensitivity in vivo, leading to effective tumor control. Collectively, these findings reveal that inflammatory signaling crosstalk between TAMs and fibroblasts is responsible for the formation of the CD10+GPR77+ CAFs, suggesting CCL18-PITPNM3 signaling is a potential therapeutic target to block the activation of this specific CAF subtype and tumor chemoresistance.

Space-confined growth of nanoscale metal-organic frameworks/Pd in hollow mesoporous silica for highly efficient catalytic reduction of 4-nitrophenol.

The development of confined growth of metal-organic frameworks (MOFs) in a nano-space remains a challenge mainly due to the spatial size randomness and inhomogeneity of host materials and the limitation of MOF species. In this study, we developed a general "stepwise vacuum evaporation" strategy, which allows the nano-confined growth of MOFs in hollow mesoporous silica nanospheres (HMSN) by the vacuum forces and the capillary effect. A series of nanoscale MOFs including ZIF-8, ZIF-90, HKUST-1, MIL-53(Cr) and UiO-66-NH2 were confinely synthesized inside the cavities of HMSN, resulting in hierarchically porous composites with core-shell structures. Further functionalization was studied by anchoring Pd to obtain UiO-66-NH2/Pd@HMSN catalyst, which exhibited excellent activity in the catalytic reduction of 4-nitrophenol to 4-aminophenol under ambient condition.