LncRNA GAS5 inhibits miR-579-3p to activate SIRT1/PGC-1α/Nrf2 signaling pathway to reduce cell pyroptosis in sepsis-associated renal injury.

Sepsis is a life-threatening condition that can lead to several organ failures including kidney. In this study, we investigated the roles of GAS5 and miR-579-3p in regulating cell pyroptosis in the sepsis-induced renal injury model. Lipopolysaccharide (LPS) treatment or cecal ligation and puncture (CLP) surgery was used to create the in vitro and in vivo sepsis-induced renal injury model. The interactions between GAS5 and miR-579-3p, and miR-579-3p and SIRT1 were determined by bioinformatic prediction, luciferase reporter assay, and RIP assay. In vitro cell pyroptosis was examined by flow cytometry marked with active caspase-1 and PI. The protein levels of IL-1ß and IL-18 induced by cell pyroptosis were quantified using ELISA assay. In vivo renal injuries were evaluated with HE and TUNEL stainings, bacterial load in serum and creatinine, and blood urea nitrogen content analyses. Expression levels of GAS5, miR-579-3p, pyroptosis, and SIRT1/PGC-1a/Nrf2 pathway-related molecules were evaluated by qRT-PCR or Western blot. GAS5 and SIRT1 were downregulated, whereas miR-579-3p was upregulated in in vitro and in vivo sepsis-induced renal injury models. GAS5 negatively and directly regulated miR-579-3p to reduce cell pyroptosis via the activation of SIRT1/PGC-1a/Nrf2 pathway. In addition, miR-579-3p suppressed PGC-1a/Nrf2 pathway to induce cell pyroptosis by directly targeting SIRT1. What's more, overexpression of GAS5, or knockdown of miR-579-3p, enhanced SIRT1 expression that led to the improved survival rate, reduced the weight loss, and relieved renal injuries in septic mice. Overexpression of GAS5 demonstrated protective effects against sepsis-induced renal injury via downregulating miR-579-3p and activating SIRT1/PGC-1α/Nrf2 pathway to inhibit cell pyroptosis.

Effects of nutritional indices and inflammatory parameters on patients received immunotherapy for non-small cell lung cancer.

OBJECTIVE: This research explored the relationship between a patient's nutritional state and inflammatory markers and the prognosis of their non-small cell lung cancer (NSCLC) treatment while receiving a combination of chemotherapy and immunotherapy. METHOD: This retrospective and single-center analysis included NSCLC patients who received a combination of chemotherapy and immunotherapy at the Department of Oncology at Shanghai Lung Hospital. Patients were categorized based on malnutrition, sarcopenia, sarcopenic obesity, and advanced-lung-cancer-inflammation-index (ALI) scores after collecting nutritional and inflammatory indices. Kaplan-Meier and the Cox models were utilized to analyze survival. RESULTS: There was a significant correlation between malnutrition, sarcopenia, sarcopenic obesity, and low ALI scores with lower overall survival (OS) and progression-free survival (PFS) (p < 0.05). Low ALI score and malnutrition were independent factors influencing patient survival in terms of both OS and PFS (p < 0.01). CONCLUSION: The nutritional and inflammatory indices of immunotherapy-treated NSCLC patients substantially affect their prognosis. Assessing these variables could aid in optimizing treatment strategies and improving patient outcomes. Additional research is required to comprehend the intricate relationship between nutrition, inflammation, and cancer progression and to develop individualized therapies.

1-(2'-Anilinyl)prop-2-yn-1-ol rearrangement for oxindole synthesis.

A synthetic method that relies on NIS (N-iodosuccinimide)-mediated cycloisomerization reactions of 1-(2'-anilinyl)prop-2-yn-1-ols to gem-3-(diiodomethyl)indolin-2-ones and 2-(iodomethylene)indolin-3-ones has been developed. The reactions were shown to be chemoselective, with secondary and tertiary alcoholic substrates exclusively giving the 3- and 2-oxindole products, respectively. In the case of the latter, the transformation features an unprecedented double 1,2-OH and 1,2-alkyl migration relay. Density functional theory (DFT) calculations based on proposed iodoaminocyclization species provide insight into this unique divergence in product selectivity.

[Effects of carbon disulfide exposure during peri-implantation on estrogen receptor-α expression in uterus and serum level of estrogen in pregnant mice].

OBJECTIVE: To evaluate the effects of carbon disulfide (CS(2)) exposure during peri-implantation on the estrogen receptor-α (ER-α) expression in the uterus and serum level of estradiol (E(2)) in pregnant mice, and to explore the mechanism of embryotoxicity of CS(2). METHODS: Healthy female mice were exposed to a single dose of CS(2) (631.4 mg/kg) or olive oil (solvent control) on gestational day (GD)3, GD4, GD5, or GD6. At different time points after exposure, the serum E(2) levels of the pregnant mice were measured by enzyme-linked immunosorbent assay, and the expression levels of ER-α in the uterus were measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot. RESULTS: Compared with the control group, the GD3, GD4, GD5, and GD6 exposure groups showed significantly decreased serum E(2) levels on day 7 of gestation (P < 0.05); the GD3 and GD5 exposure groups showed significantly decreased serum E(2) levels on day 6 of gestation (P < 0.05). The expression level of ER-α in the GD 4 exposure group was 23.6% lower than that in the control group on day 5 of gestation, and the expression level of ER-α in the GD 5 exposure group was 72.9% lower than that in the control group on day 6 of gestation (P < 0.05); the GD 3 and GD 6 exposure groups showed lower expression levels of ER-α than the control group at any time point, but no significant difference was found (P > 0.05). CONCLUSION: CS(2) exposure during peri-implantation can reduce the ER-α expression in the uterus and the serum level of E(2) in pregnant mice, which may be one of the mechanisms of embryotoxicity of CS(2).

Time trends in myopia and high myopia prevalence in young university adults in China.

AIM: To investigate time trends in myopia and high myopia prevalence over 6y among young university adults in China. METHODS: This is a 6-year series cross-sectional study from 2016 to 2021. Totally 4910 freshmen were enrolled and completed a questionnaire concerning age, gender, and disease history. Students with eye diseases were excluded after a detailed eye examination. The refractive status was measured by non-cycloplegic objective refraction and ocular parameters were measured by Lenstar 900. The examination followed the same protocol each year. Trends over time in myopia and high myopia prevalence, as well as ocular biometry parameters, were analyzed. RESULTS: From 2016 to 2021, the axial length (AL) and corneal radius (CR) increased significantly (P=0.002 for AL; P=0.04 for CR). However, the spherical equivalent (SE) and the ratio of axial length to the corneal radius (AL/CR) did not change significantly (P=0.59 for SE; P=0.24 for AL/CR). The frequency of AL ≥26.0 mm increased from 26.6% in 2016 to 29.3% in 2021 (P=0.05 for trend). The prevalence of myopia and high myopia did not change significantly in our study (P≥0.18). Compared to a similar cross-sectional study conducted 10 years ago, the prevalence of myopia decreased significantly (94.9% vs 91.8%, P<0.001). Whereas the prevalence of high myopia increased largely (18.12% vs 27.6%, P<0.001). CONCLUSION: The prevalence of high myopia increases in young university adults during 10y period. Myopia control should begin earlier in childhood. However, these interventions are still needed for high myopia even in young adulthood.

The involvement of systemic RNA interference deficient-1-like (SIL1) in cellular dsRNA uptake in Acyrthosiphon pisum.

Systemic RNA interference deficient-1-like (SIL1) is considered a core component in dsRNA uptake in some insect species. Investigation related to the potential function of SIL1 in dsRNA uptake can contribute to a further understanding of RNA interference (RNAi) mechanisms in insects and agricultural pest control. However, the role of SIL1 in dsRNA uptake in insects such as aphids remains controversial. We have thoroughly analyzed the role of SIL1 from the model aphid Acyrthosiphon pisum (ApSIL1) in cellular dsRNA to clarify its function. First, the induced expression of ApSIL1 upon dsRNA oral exposure provided a vital clue for the possible involvement of ApSIL1 in cellular dsRNA uptake. Subsequent in vivo experiments using the RNAi-of-RNAi approach for ApSIL1 supported our hypothesis that the silencing efficiencies of reporter genes were reduced after inhibition of ApSIL1 expression. The impaired biological phenotypes of aphids, including cumulative average offspring, deformities of the nymph, and mortality upon pathogen infection, were then observed in the treatment group. Thereafter, in vitro dual-luciferase reporter assay showed compelling evidence that the luciferin signal was significantly attenuated when dsluciferase or dsGFP was transferred into ApSIL1-transfected Drosophila S2 cells. These observations further confirmed that the signal of Cy3-labeled dsRNA was rapidly attenuated with time in ApSIL1-transfected Drosophila S2 cells. Overall, these findings conclusively establish that ApSIL1 is involved in dsRNA uptake in A. pisum.

Study of substrate dependence on the chemoselectivity of the gold-catalysed cycloisomerisation of aryl substituted 1,7-enynes.

The effects of starting material substitution patterns on reaction selectivity for the gold(I)-catalysed cycloisomerisations of aryl substituted 1,7-enynes were investigated. The results indicated the chemoselectivity of the reaction to be highly substrate and catalyst dependent. Either the piperidine or the tetrahydro-1H-azepine product was obtained in moderate to excellent yields depending on the steric and/or electronic nature of the substrate and the gold(I) catalyst. Overall, six-membered nitrogen ring formation was found to be favoured in reactions with 1,7-enyne derivatives containing a disubstituted alkene moiety or not bearing a sterically bulky substituent or a gold(I) catalyst with a pendant sterically unencumbered phosphine ligand. Formation of the seven-membered nitrogen heterocycle was observed in reactions where the substrate contained a tetrasubstituted alkene unit or a sterically demanding substituent.

[Effect of γδ T cells on the Proliferation, Apoptosis and Autophagy of Multiple Myeloma Cells].

AbstractObjective: To investigate the effect of γδ T cells on the proliferation, apoptosis and autophagy of multiple myeloma cells. METHODS: Peripheral blood mononuclear cells (PBMNC) were isolated from healthy volunteers, and stimulated with zoledronic acid (Zol) in combination with rhIL-2. Flow cytometry analysis was used to detected the purity of γδ T cells. γδ T cells were collected and co-cultured with RPMI-8226 or U-266 cells at different effector target ratios. The proliferation of RPMI-8226 or U-266 cell lines were detected by CCK-8. Cell cycle and cell apoptosis were detected by flow cytometry and Western blot．The expressions of autophagy-related proteins were detected by Western blot. RESULTS: γδ T cells can be expanded in vitro. γδ T cells could inhibit the proliferation of RPMI-8226 or U-266 cells, induced cell cycle arrest and promoted apoptosis in an effector target-dependent manner. In addition, γδ T cells could induce autophagy of myeloma cells, inhibited the expression of autophagy-related PI3K, P-AKT and P-mTOR, while increased the expression of AMPK and Beclin-1. CONCLUSION: γδ T cells can inhibit the proliferation of RPMI-8226 and U-266 myeloma cells, induce cell cycle arrest, promote apoptosis, and enhance autophagy in vitro. The mechanism may be related to inhibition of PI3K/AKT/mTOR signaling pathway and/or activation of AMPK/Beclin-1 signaling pathway.

SlMYC2 mediates stomatal movement in response to drought stress by repressing SlCHS1 expression.

Drought stress limits plant development and reproduction. Multiple mechanisms in plants are activated to respond to stress. The MYC2 transcription factor is a core regulator of the jasmonate (JA) pathway and plays a vital role in the crosstalk between abscisic acid (ABA) and JA. In this study, we found that SlMYC2 responded to drought stress and regulated stomatal aperture in tomato (Solanum lycopersicum). Overexpression of SlMYC2 repressed SlCHS1 expression and decreased the flavonol content, increased the reactive oxygen species (ROS) content in guard cells and promoted the accumulation of JA and ABA in leaves. Additionally, silencing the SlCHS1 gene produced a phenotype that was similar to that of the MYC2-overexpressing (MYC2-OE) strain, especially in terms of stomatal dynamics and ROS levels. Finally, we confirmed that SlMYC2 directly repressed the expression of SlCHS1. Our study revealed that SlMYC2 drove stomatal closure by modulating the accumulation of flavonol and the JA and ABA contents, helping us decipher the mechanism of stomatal movement under drought stress.

[Research Progress on Regulating Autophagy in the Treatment of Multiple Myeloma --Review].

Abstract　　Autophagy is a process in which cells in eukaryotes degrades abnormal proteins and organelles, thus it possesses important effects on the survival of normal cells and tumor cells. The related studies have shown that autophagy is widely present in the life activities of myeloma cells, which not only protects myeloma cells, but also induces death, and plays an important role in survival, proliferation, invasion and migration of myeloma cells and the treatment of multiple myeloma. This review focuses on the progress of regulating autophagy in the treatment of multiple myeloma.

Clinicopathological characteristics of renal solitary fibrous tumor: A single institution experience.

To analyze the clinical characteristics, treatment modalities and outcomes of adult renal solitary fibrous tumors (SFT) treated at a single institution. Demographic, diagnostic, surgical, and pathological findings of patients who had undergone radical nephrectomy (RN) due to renal SFT were collected from the database of a single institution and were retrospectively reviewed. Ten patients (6 men and 4 women) were diagnosed with renal SFT in our institution between January 1, 2000 and December 31, 2016. The mean age was 50.9 ±â€Š8.2 years (range, 38-63 years). Of the 10 patients, 6 were asymptomatic, 2 presented with flank pain, 1 presented with abdominal discomfort, and 1 presented with haematuria. Computed tomography scans were obtained for all patients. Open RN was performed on 6 patients, and laparoscopic RN was performed on 4 patients. The mean tumor size was 10.23 ±â€Š4 cm (range, 5.3-19 cm). Pathological diagnosis revealed that the tumors in 8 patients were benign, while those in the other 2 patients were malignant renal SFT. No recurrence occurred during a mean follow-up period of 47.3 ±â€Š21.5 months (range, 16-85 months). Renal SFT is extremely rare, and its diagnosis may be challenging because of a lack of typical imaging manifestations. RN is a safe treatment modality for benign or low-grade malignant renal SFT, ensuring favorable outcomes.

Cellular Temperature Imaging Technology Based on Single-molecule Quantum Coherent Modulation / 生物化学与生物物理进展

ObjectiveCellular temperature imaging can assist scientists in studying and comprehending the temperature distribution within cells, revealing critical information about cellular metabolism and biochemical processes. Currently, cell temperature imaging techniques based on fluorescent temperature probes suffer from limitations such as low temperature resolution and a limited measurement range. This paper aims to develop a single-cell temperature imaging and real-time monitoring technique by leveraging the temperature-dependent properties of single-molecule quantum coherence processes. MethodsUsing femtosecond pulse lasers, we prepare delayed and phase-adjustable pairs of femtosecond pulses. These modulated pulse pairs excite fluorescent single molecules labeled within cells through a microscopic system, followed by the collection and recording of the arrival time of each fluorescent photon. By defining the quantum coherence visibility (V) of single molecules in relation to the surrounding environmental temperature, a correspondence between V and environmental temperature is established. By modulating and demodulating the arrival times of fluorescent photons, we obtain the local temperature of single molecules. Combined with scanning imaging, we finally achieve temperature imaging and real-time detection of cells. ResultsThis method achieves high precision (temperature resolution<0.1°C) and a wide temperature range (10-50°C) for temperature imaging and measurement, and it enables the observation of temperature changes related to individual cell metabolism. ConclusionThis research contributes to a deeper understanding of cellular metabolism, protein function, and disease mechanisms, providing a valuable tool for biomedical research.

Raman Spectroscopy Analysis of The Temporal Heterogeneity in Lung Cell Carcinogenesis Induced by Benzo(a)pyrene / 生物化学与生物物理进展

ObjectiveTemporal heterogeneity in lung cancer presents as fluctuations in the biological characteristics, genomic mutations, proliferation rates, and chemotherapeutic responses of tumor cells over time, posing a significant barrier to effective treatment. The complexity of this temporal variance, coupled with the spatial diversity of lung cancer, presents formidable challenges for research. This article will pave the way for new avenues in lung cancer research, aiding in a deeper understanding of the temporal heterogeneity of lung cancer, thereby enhancing the cure rate for lung cancer. MethodsRaman spectroscopy emerges as a powerful tool for real-time surveillance of biomolecular composition changes in lung cancer at the cellular scale, thus shedding light on the disease’s temporal heterogeneity. In our investigation, we harnessed Raman spectroscopic microscopy alongside multivariate statistical analysis to scrutinize the biomolecular alterations in human lung epithelial cells across various timeframes after benzo(a)pyrene exposure. ResultsOur findings indicated a temporal reduction in nucleic acids, lipids, proteins, and carotenoids, coinciding with a rise in glucose concentration. These patterns suggest that benzo(a)pyrene induces structural damage to the genetic material, accelerates lipid peroxidation, disrupts protein metabolism, curtails carotenoid production, and alters glucose metabolic pathways. Employing Raman spectroscopy enabled us to monitor the biomolecular dynamics within lung cancer cells in a real-time, non-invasive, and non-destructive manner, facilitating the elucidation of pivotal molecular features. ConclusionThis research enhances the comprehension of lung cancer progression and supports the development of personalized therapeutic approaches, which may improve the clinical outcomes for patients.

The prognostic significance of high/positive expression of tissue VEGF in ovarian cancer.

BACKGROUND & AIM: At present, numerous reports have shown that high/positive expression of tissue vascular endothelial growth factor (VEGF) may be associated with the prognosis of patients with ovarian cancer. However, their results still remained controversy. Thus, this meta-analysis was designed to analyze and assess the prognostic value of tissue VEGF expression in patients with ovarian cancer. METHOD: We searched PubMed, Embase, Cochrane Library and Web of Science to October, 2017. Hazard Ratio (HR) with its 95% confidence intervals (CIs) was used to evaluate the association between high/positive expression of tissue VEGF and the prognosis of ovarian cancer patients. All statistical analyses were performed using standard statistical procedures provided in RevMan 5.2. RESULT: A total of 18 studies (including 1145 patients) were included for this meta-analysis. The positive/high expression of tissue VEGF had an obvious association with overall survival (OS) (HR 2.24, 95% CI 1.36-3.70; P=0.002), progression-free survival (PFS) (HR 1.60, 95% CI 1.11-2.31; P=0.01) and disease-free survival (DFS) (HR 3.49, 95% CI 1.27-9.56; P=0.02) of patients with ovarian cancer respectively. CONCLUSION: The present meta-analysis indicated that positive/high expression of tissue VEGF may have a close association with survival of ovarian cancer.

Recent advance in genetics of epilepsy of infancy with migrating focal seizure / 中华神经医学杂志

Epilepsy of infancy with migrating focal seizure (EIMFS) is a rare drug-resistant epilepsy syndrome with characteristic migrating EEG presentation. In recent years, with increased discovery of new pathogenic genes in this syndrome, our knowledge and understanding on pathophysiological mechanisms of this syndrome have been broadened. This article systematically summarizes the genes associated with EIMFS that have been reported at home and abroad to expand clinicians' understanding of the disease and provide references for identifying the disease.

Research progress of opaque bubble layer created in corneal stroma during femtosecond laser surgery / 国际眼科杂志(Guoji Yanke Zazhi)

Femtosecond laser-assisted laser in situ keratomileusis(FS-LASIK)and small incision lenticule extraction(SMILE)are the mainstream corneal refractive surgeries at present. Despite efficacy, safety and predictability they have showed in refractive error correction, there are still complications relating to femtosecond laser, such as suction loss and opaque bubble layer(OBL), due to that the production of corneal flap or lenticule is dependent on the femtosecond laser. OBL is a complication that is unique to femtosecond laser surgery and the bubbles are generated from photo-disruptive effect towards corneal tissues which consisted of water vapor and carbon dioxide, and OBL gradually formed when the bubbles are trapped in the stroma. The bubbles can influence the intraoperative manipulation and postoperative visual quality. This review discusses the mechanism, grading, classification, and influencing factors of OBL and its effects on intraoperative manipulations and postoperative recovery, in the hope of providing reference and basis for further clinical studies.

Effect and mechanism of p-hydroxybenzaldehyde on experimental intestinal fibrosis / 中国药理学通报

Aim To investigate the effect of p-hydroxybenzaldehyde ( HD) on intestinal fibrosis in mice based on mouse intestinal fibrosis model and in vitro EMT model,and to explore the underlying mechanism Methods HE staining, Masson staining, immunohisto-chemistry ,qPCR, Western blot and other experimental methods were used to verify the effect of HD on intestinal fibrosis in mice and the potential mechanism. Results In vivo experiments showed that compared with the normal group, the DSS-induced intestinal fibrosis model group had shortened colon, increased colon his-topathological score, increased collagen volume fraction, and significantly increased collagen I expression. After treatment with 4, 10, and 25 mg • kg

Role of Bone Marrow Mesenchymal Stromal Cells in Attenuating Inflammatory Reaction in Lipopolysaccaride-induced Acute Kidney Injury of Rats Associated with TLR4-NF-κB Signaling Pathway Inhibition.

Bone marrow mesenchymal stromal cells (BMSCs) have positive therapeutic effects on inflammation associated diseases. However, the underlying mechanism is largely unknown. This study was conducted to investigate whether BMSCs could alleviate the inflammation reaction in lipopolysaccaride (LPS)-induced acute kidney injury (septic-AKI) of rats via inhibition of toll-like receptors (TLR4)-nuclear factor-kappa B (NF-κB) signaling pathway. The septic-AKI rat model was established by injecting the 1ml/mg LPS through the femoral vein. Based on this model, rats were subjected to BMSC transplantation, PDTC (a kind of NF-κB inhibitor) administration alone, and combined treatment of the first two together. Results showed that LPS treatment caused the increases of the concentration of blood urea nitrogen (BUN) and serum creatinine (SCr), accompanied by tissue injury and the up-regulation of TLR4 and NF-κB, that was its key downstream signaling molecule, in both mRNA and protein level. Notably, it has been found that BMSCs transplantation significantly reversed the already upregulated concentration of BUN and SCr, dramatically attenuated the event of the tissue injury, and prominently reduced mortality after AKI. These were paralleled by down-regulation of the level of TLR4 and NF-κB. These effects of BMSCs transplantation were similar to those of PDTC treatment. Importantly, the effects in the combination therapy of BMSCs transplantation and PDTC group were much stronger than those of either BMSCs or PDTC used alone. These findings suggest that BMSCs transplantation contributes to therapeutic effects in LPS-induced AKI rat model, and that the most obvious effects occurred in the combined treatment group, with BMSCs and PDTC together, which was tightly associated with inhibition of the TLR4-NF-κB signaling pathway.

Development and applications of two colorimetric and fluorescent indicators for Hg2+ detection.

Two rhodamine-active probes RBAI (Rhodamine B-di-Aminobenzene-phenyl Isothiocyanate) and RGAI (Rhodamine 6G-di-Aminobenzene-phenyl Isothiocyanate) were designed, synthesized and characterized. The probes were developed as fluorescent and colorimetric chemodosimeters in ethanol-water solution with a broad pH span (5-10) and high selectivity toward Hg2+ but no significant response toward other common competitive cations. The Hg2+-promoted ring opening of spirolactam of the rhodamine moiety induced cyclic guanylation of the thiourea moiety, which resulted in the dual chromo- and fluorogenic observation (off-on). Cytotoxicity and bioimaging studies by L929 living cells and living mice indicated that the probes were negligible cytotoxicity, cell permeable and suitable for detecting Hg2+ in biological environments. Moreover, the new probes not only displayed excellent abilities for the successful detection of Hg2+ in L929 living cells and living mice but also able to detect Hg2+ by adsorbing on solid surfaces and quantitative detection of Hg2+ in real water samples with good recovery (more than 90%), indicating that they have promising prospect for application for Hg2+ sensing in environmental and biological sciences.

Recent advance in sialidosis / 中华神经医学杂志

Sialidosis is a rare autosomal recessive genetic disorder, and has a series of clinical symptoms and signs caused by neuraminidase 1 ( NEU1) gene mutations. This article reviews the etiology, clinical features, diagnoses, treatments and prognoses of sialidosis in order to improve the understanding and diagnosis of this disease and reduce the misdiagnosis of this disease.