Time patterns in online survey completion and offline psychological symptoms among college students in China.

Background: Online psychological surveys allow for swift data collection among college students, thus providing a foundation for psychological interventions, particularly during emergent public health events. However, the association between online survey completion behaviors and offline psychological symptoms has yet to be explored. Methods: A large-scale web-based survey was conducted from December 31, 2022, to January 7, 2023, involving 22,624 participants. Psychological symptoms were assessed using standardized measures, while the time taken to complete the survey and the time of completion were recorded by the online survey platform. Results: As the time duration increased, the prevalence of anxiety, depression, insomnia, and PTSD also increased significantly (P for trend < 0.001). The highest odds ratios were observed in the longer duration group. Only a longer duration was significantly associated with PTSD. The time period for completing the questionnaire from 7 p.m. to 10 p.m. was found to be significantly linked with anxiety symptoms and depression symptoms. Conversely, completing the questionnaire at other times was specifically associated with anxiety symptoms and insomnia symptoms. The prolonged duration needed to complete the questionnaire was more closely related to the comorbidity of anxiety, depression, and insomnia than to the comorbidity of those symptoms with PTSD. When questionnaires were completed during other times, specifically referring to the late-night and early morning hours, individuals were more likely to exhibit comorbid symptoms of insomnia. Conclusion: The study identified the specific associations between time durations, time points for completing online survey, and psychological symptoms/comorbidity among college students. Further exploration of their causal relationships and the underlying mechanisms is warranted.

Trajectory model to analyse the effect of multi-metal exposures on sperm parameters and sex hormones of the MARHCS cohort in China.

BACKGROUND: At present, several cross-sectional studies have found that exposure to metal/metalloid elements is closely associated with male reproduction. However, the long-term effects of metal exposure on male reproduction have not been explored. METHODS: In 2013, 796 volunteers were recruited, followed by first and second follow-ups in 2014 and 2015. Urine, semen, and blood samples were collected at each stage to examine urinary metal/metalloid levels, sperm parameters, and sex hormones. Initially, the latent class trajectory model (LCTM) was utilized to analyze the trajectories of urinary metals. Subsequently, the effects of urinary metal trajectories on semen parameters and sex hormones were examined using the linear mixed model. Finally, the impact of urinary metal trajectories on the classification of semen quality (normal or abnormal) was evaluated using the generalized linear mixed model. RESULTS: Among the 18 metals/metalloids studied, trajectories were formed by 6 of them (Li, Al, Fe, Zn, As, Rb). Further analysis using the linear mixed model and the generalized linear mixed model revealed that Li was negatively correlated with semen volume, and sperm motility (P<0.05). The maximum-decreasing trajectory group had a detrimental effect on semen quality (OR=1.75, 95%CI: 1.22, 2.53) compared to the minimum-stable trajectory group. Al showed negative associations with sperm concentration, total sperm count, and normal morphology (P<0.05). Rb was positively associated with progressive motility (P<0.05). The high-stable trajectory group exhibited a protective effect on semen quality (OR=0.66, 95%CI: 0.49, 0.90) compared to the low-stable trajectory group. Additionally, Fe was observed to have a negative relationship with follicle-stimulating hormone (FSH) (P<0.05), and Rb exhibited a negative correlation with progesterone (P) (P<0.05). CONCLUSION: Our three-year cohort study provides new evidence that Li and Al have a negative impact on semen quality, whereas Rb is associated with beneficial effects. Additionally, Rb and Fe are endocrine disruptors of sex hormones.

Deficiency of SIAH1 promotes the formation of filopodia by increasing the accumulation of FASN in liver cancer.

It has been shown that the formation of filopodia is a key step in tumor cell metastasis, but there is limited research regarding its mechanism. In this study, we demonstrated that fatty acid synthase (FASN) promoted filopodia formation in liver cancer cells by regulating fascin actin-bundling protein 1 (FSCN1), a marker protein for filopodia. Mechanistically, on the one hand, the accumulation of FASN is caused by the enhanced deubiquitination of FASN mediated by UCHL5 (ubiquitin c-terminal hydrolase L5). In this pathway, low expression of SIAH1 (Seven in absentia homolog 1) can decrease the ubiquitination and degradation of ADRM1 (adhesion regulating molecule 1) thereby increasing its protein level, which will recruit and activate the deubiquitination enzyme UCHL5, leading to FASN undergo deubiquitination and escape from proteasomal degradation. On the other hand, the accumulation of FASN is related to its weakened ubiquitination, where SIAH1 directly acts as a ubiquitin ligase toward FASN, and low expression of SIAH1 reduces the ubiquitination and degradation of FASN. Both the two pathways are involved in the regulation of FASN in liver cancer. Our results reveal a novel mechanism for FASN accumulation due to the low expression of SIAH1 in human liver cancer and suggest an important role of FASN in filopodia formation in liver cancer cells.

Mixture of Synthetic Plant Volatiles Attracts More Stick Tea Thrips Dendrothrips minowai Priesner (Thysanoptera: Thripidae) and the Application as an Attractant in Tea Plantations.

The stick tea thrip (Dendrothrips minowai) is one of the most serious sucking pests of tea plants (Camellia sinensis) in China, North Korea, and Japan. Plant volatile lures are widely used for both monitoring and mass trapping. Previously, we demonstrated that sticky traps baited with p-anisaldehyde, eugenol, farnesene, or 3-methyl butanal captured significantly more D. minowai in tea plantations, with p-anisaldehyde notably capturing the most. In this study, we showed that D. minowai adults exhibited significantly higher attraction to mixtures of p-anisaldehyde, eugenol, and farnesene compared to an equivalent dose of p-anisaldehyde alone in H-tube olfactometer assays under laboratory conditions. Moreover, in field experiments conducted in 2022, rubber septa impregnated with a ternary blend of p-anisaldehyde, eugenol, and farnesene (at 3-4.5 mg and a ratio of 3:1:1) captured the highest number of adults on sticky traps, outperforming traps bailed with individual components or a solvent control over two weeks. Significantly, the mass trapping strategy employing these lures achieved control efficacies ranging from 62.8% to 70.7% when compared to traps without attractant, which achieved control efficacies of only 14.2% to 35.4% across three test sites in 2023. These results indicate that the combination of p-anisaldehyde, eugenol, and farnesene exhibits an additive or synergistic effect on D. minowai. In conclusion, our findings establish a theoretical framework and provide practical technological support for integrating attractant-based strategies into comprehensive thrips management strategies.

DHTPY-Cu@ZOL-Enhanced Photodynamic Therapy: A Strategic Platform for Advanced Treatment of Drug-Resistant Bacterial Wound Infections.

Purpose: This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This approach is designed to address the hypoxic conditions often found in bacterial infections and aims to boost the effectiveness of photodynamic therapy (PDT) by ensuring sufficient oxygen supply for reactive oxygen species (ROS) generation. Methods: Our approach involved the synthesis of dihydroxyl triphenyl vinyl pyridine (DHTPY)-Cu@zoledronic acid (ZOL) nanozyme particles. We initially synthesized DHTPY and then combined it with copper nanozymes to form the DHTPY-Cu@ZOL composite. The nanozyme's size, morphology, and chemical properties were characterized using various techniques, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy. We conducted a series of in vitro and in vivo tests to evaluate the photodynamic, antibacterial, and wound-healing properties of the DHTPY-Cu@ZOL nanozymes, including their oxygen-generation capacity, ROS production, and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA). Results: The DHTPY-Cu@ZOL exhibited proficient H2O2 scavenging and oxygen generation, crucial for enhancing PDT in oxygen-deprived infection environments. Our in vitro analysis revealed a notable antibacterial effect against MRSA, suggesting the nanozymes' potential to disrupt bacterial cell membranes. Further, in vivo studies using a diabetic rat model with MRSA-infected wounds showed that DHTPY-Cu@ZOL markedly improved wound healing and reduced bacterial presence, underscoring its efficacy as a non-antibiotic approach for chronic infections. Conclusion: Our study suggests that DHTPY-Cu@ZOL is a highly promising approach for combating antibiotic-resistant microbial pathogens and biofilms. The biocompatibility and stability of these nanozyme particles, coupled with their improved PDT efficacy position them as a promising candidate for clinical applications.

Efficacy of the efficacy between dexamethasone versus triamcinolone acetonide after cataract surgery: A systematic review and meta-analysis.

PURPOSE: To evaluate the clinical effects between dexamethasone and triamcinolone acetonide (TA) after phacoemulsification and intraocular lens implantation among cataract patients. METHODS: Pubmed, Embase, and the Cochrane Library were searched for studies published up to August 2020. The primary outcome was intraocular pressure. The secondary outcomes were the logarithm of the minimum angle of resolution (logMAR), anterior chamber cell, and anterior chamber flare. The pooled effect sizes were expressed as weighted mean differences (WMDs) or standardized mean differences (SMDs) of 95% confidence intervals (95% CIs). Cochrane Collaboration risk of bias tool and Newcastle-Ottawa scale criteria were used for the quality assessment of included studies. RESULTS: Seven relevant studies met the inclusion criteria. For the primary outcome, there was no significant difference between TA injection and dexamethasone in comparing intraocular pressure (IOP) (SMD = 0.22, 95% confidence interval [CI] [-0.29, 0.73], P = .408; I²â€…= 86.9%) in the first day after treatment and last day of assessment. For the secondary outcomes, the logMAR (WMD = 0.01, 95% CI [-0.06, 0.08]) and the anterior chamber flare (SMD = 0.08, 95% CI [-0.01, 0.18], P = .087; I²â€…= 0%) showed no differences. However, the amount of anterior chamber cells (SMD = -0.21, 95% CI [-0.42, -0.01], P = .044; I²â€…= 0%) in the TA injection on the first day postoperative was higher than for dexamethasone. After treatment, there was no difference between the 2 groups. CONCLUSIONS: This study supports that there were no differences in IOP, logMAR, and anterior chamber flare between TA injection and dexamethasone among cataract patients. TA injection treatment on the first day showed higher amounts of anterior chamber cells than with dexamethasone.

CXCL1/IGHG1 signaling enhances crosstalk between tumor cells and tumor-associated macrophages to promote MC-LR-induced colorectal cancer progression.

Microcystin-leucine arginine (MC-LR) is a common cyantotoxin produced by hazardous cyanobacterial blooms, and eutrophication is increasing the contamination level of MC-LR in drinking water supplies and aquatic foods. MC-LR has been linked to colorectal cancer (CRC) progression associated with tumor microenvironment, however, the underlying mechanism is not clearly understood. In present study, by using GEO, KEGG, GESA and ImmPort database, MC-LR related differentially expressed genes (DEGs) and pathway- and gene set-enrichment analysis were performed. Of the three identified DEGs (CXCL1, GUCA2A and GDF15), CXCL1 was shown a positive association with tumor infiltration, and was validated to have a dominantly higher upregulation in MC-LR-treated tumor-associated macrophages (TAMs) rather than in MC-LR-treated CRC cells. Both CRC cell/macrophage co-culture and xenograft mouse models indicated that MC-LR stimulated TAMs to secrete CXCL1 resulting in promoted proliferation, migration, and invasion capability of CRC cells. Furtherly, IP-MS assay found that interaction between TAMs-derived CXCL1 and CRC cell-derived IGHG1 may enhance CRC cell proliferation and migration after MC-LR treatment, and this effect can be attenuated by silencing IGHG1 in CRC cell. In addition, molecular docking analysis, co-immunoprecipitation and immunofluorescence further proved the interactions between CXCL1 and IGHG1. In conclusion, CXCL1 secreted by TAMs can trigger IGHG1 expression in CRC cells, which provides a new clue in elucidating the mechanism of MC-LR-mediated CRC progression.

Correlation Analysis of Digital Mammography, Ultrasonography, and Pathologic Features in Pure Invasive Micropapillary Carcinoma of the Breast (PIMPC).

Purpose: This study determined the digital mammography and ultrasonography imaging features of pure invasive micropapillary carcinoma of the breast (PIMPC) and the correlation with pathologic features. Patients Methods: Nineteen patients diagnosed with PIMPC at Yantaishan Hospital from October 2015 to February 2022 were included in the study group. Forty patients with breast masses diagnosed as nonspecific invasive ductal carcinoma of the breast (NIDC) from July to December 2021 were included in the control group. Digital mammography and ultrasonography features were compared between the two groups. Results: Patients with PIMPC had a younger age profile compared to patients with NIDC (P=0.017). Moreover, PIMPC masses were smaller than NIDC masses (P=0.040). Imaging features analysis revealed significant differences in age groups (<45 years: χ²=5.971, P=0.044) and the presence of spiculations or the crab claw sign (χ²=8.583, P=0.004) between patients with PIMPC and NIDC. However, there were no statistically significant differences in the presence of calcifications, blood flow grading, pathologic molecular subtypes between the study and control groups. The Ki-67 proliferative index (χ²=1.052, P=0.389), vascular invasion (χ²=2.263, P=0.197), and lymph node metastasis (χ²=1.968, P=0.386) showed no significant differences between PIMPC and NIDC patients. Conclusion: PIMPC imaging features show specificity, such as tiny breast masses, spiculated edges, or crab claw-like patterns, and malignant signs appeared when the lesion was <2 cm in diameter. PIMPC mainly occurs in middle-aged women 45-59 y of age. Patients with PIMPC and NIDC of the breast are frequently associated with lymph node metastases and greater than one-half of the cases (74%) were shown to have a Ki-67 index >30%, suggesting a significant risk of recurrence and metastasis. Early therapeutic care for these patients is crucial. These results warrant further validation with additional samples from several centers due to the limited single-center sample size in the current study.

Is intravoxel incoherent motion magnetic resonance imaging useful for predicting hepatocellular cancer recurrence and invasion of the peritumoral zone after transarterial chemoembolization?

PURPOSE: We evaluated the potential role of intravoxel incoherent motion (IVIM) in predicting the therapeutic response and peritumoral invasion in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). MATERIALS AND METHODS: We enrolled 47 patients previously treated with TACE between January 2018 and December 2021. We evaluated the IVIM-derived metrics [apparent diffusion coefficient (ADC), D, D*, f] in the TACE-treated, peritumoral, and parenchymal areas of the liver. RESULTS: The ADCtace and Dtace values (1.13 ± 0.22 × 10-3 m2/s vs 0.95 ± 0.13 × 10-3 mm2/s, 1.28 ± 0.27 × 10-3 mm2/s vs 1.07 ± 0.3 × 10-3 mm2/s, P < 0.05) were higher in the non-progressing groups than in the progressing groups in the TACE-treated areas. Dpt represented the D values in the peritumoral area, which can distinguish between the progressive and non-progressive groups with an AUC of 0.73. The Dstd values, which represent the D values in the peritumoral area normalized by the D values in the liver parenchyma in the non-progressing groups (1.10 ± 0.14 × 10-3 mm2/s), were higher than those of the progressing groups (0.93 ± 0.17 × 10-3 mm2/s). CONCLUSION: The ADCtace, Dtace, Dpt, and Dstd values reflect the changes in the microstructure of the progressive and non-progressive groups after TACE treatment, showing robust diagnostic performances in predicting the therapeutic response and peritumoral invasion.

Alterations of the cerebral microstructure in patients with noise-induced hearing loss: A diffusion tensor imaging study.

OBJECTIVE: To explore the changes in the cerebral microstructure of patients with noise-induced hearing loss (NIHL) using diffusion tensor imaging (DTI). METHOD: Overall, 122 patients with NIHL (mild [MP, n = 79], relatively severe patients [including moderate and severe; RSP, n = 32], and undetermined [lost to follow-up, n = 11]) and 84 healthy controls (HCs) were enrolled. All clinical data, including age, education level, hearing threshold, occupation type, noise exposure time, and some scale scores (including the Mini-Mental State Examination [MMSE], tinnitus handicap inventory [THI], and Hamilton Anxiety Scale [HAMA]), were collected and analyzed. All participants underwent T1WI3DFSPGR and DTI, and tract-based spatial statistics and region of interest (ROI) analysis were used for assessment. RESULTS: The final sample included 71 MP, 28 RSP, and 75 HCs. The HAMA scores of the three groups were significantly different (p < .05). The noise exposure times, hearing thresholds, and HAMA scores of the MP and RSP were significantly different (p < .05). The noise exposure time was positively correlated with the hearing threshold and negatively correlated with the HAMA scores (p < .05), whereas the THI scores were positively correlated with the hearing threshold (p < .05). DTI analysis showed that all DTI parameters (fractional anisotropy [FA], axial diffusivity [AD], mean diffusivity [MD], and radial diffusivity [RD]) were significantly different in the left inferior longitudinal fasciculus (ILF) and left inferior fronto-occipital fasciculus (IFOF) for the three groups (p < .05). In addition, the FA values were significantly lower in the bilateral corticospinal tract (CST), right fronto-pontine tract (FPT), right forceps major, left superior longitudinal fasciculus (temporal part) (SLF), and left cingulum (hippocampus) (C-H) of the MP and RSP than in those of the HCs (p < .05); the AD values showed diverse changes in the bilateral CST, left IFOF, right anterior thalamic radiation, right external capsule (EC), right SLF, and right superior cerebellar peduncle (SCP) of the MP and RSP relative to those of the HC (p < .05). However, there were no significant differences among the bilateral auditory cortex ROIs of the three groups (p > .05). There was a significant negative correlation between the FA and HAMA scores for the left IFOF/ILF, right FPT, left SLF, and left C-H for the three groups (p < .05). There was a significant positive correlation between the AD and HAMA scores for the left IFOF/ILF and right EC of the three groups (p < .05). There were significantly positive correlations between the RD/MD and HAMA scores in the left IFOF/ILF of the three groups (p < .05). There was a significant negative correlation between the AD in the right SCP and noise exposure time of the MP and RSP groups (p < .05). The AD, MD, and RD in the left ROI were significantly positively correlated with hearing threshold in the MP and RSP groups (p < .05), whereas FA in the right ROI was significantly positively correlated with the HAMA scores for the three groups (p < .05). CONCLUSION: The changes in the white matter (WM) microstructure may be related to hearing loss caused by noise exposure, and the WM structural abnormalities in patients with NIHL were mainly located in the syndesmotic fibers of the temporooccipital region, which affected the auditory and language pathways. This confirmed that the auditory pathways have abnormal structural connectivity in patients with NIHL.

Thidiazuron combined with cyclanilide modulates hormone pathways and ROS systems in cotton, increasing defoliation at low temperatures.

Low temperatures decrease the thidiazuron (TDZ) defoliation efficiency in cotton, while cyclanilide (CYC) combined with TDZ can improve the defoliation efficiency at low temperatures, but the mechanism is unknown. This study analyzed the effect of exogenous TDZ and CYC application on cotton leaf abscissions at low temperatures (daily mean temperature: 15°C) using physiology and transcriptomic analysis. The results showed that compared with the TDZ treatment, TDZ combined with CYC accelerated cotton leaf abscission and increased the defoliation rate at low temperatures. The differentially expressed genes (DEGs) in cotton abscission zones (AZs) were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to compare the enriched GO terms and KEGG pathways between the TDZ treatment and TDZ combined with CYC treatment. TDZ combined with CYC could induce more DEGs in cotton leaf AZs at low temperatures, and these DEGs were related to plant hormone and reactive oxygen species (ROS) pathways. CYC is an auxin transport inhibitor. TDZ combined with CYC not only downregulated more auxin response related genes but also upregulated more ethylene and jasmonic acid (JA) response related genes at low temperatures, and it decreased the indole-3-acetic acid (IAA) content and increased the JA and 1-aminocyclopropane-1-carboxylic acid (ACC) contents, which enhanced cotton defoliation. In addition, compared with the TDZ treatment alone, TDZ combined with CYC upregulated the expression of respiratory burst oxidase homologs (RBOH) genes and the hydrogen peroxide content in cotton AZs at low temperatures, which accelerated cotton defoliation. These results indicated that CYC enhanced the TDZ defoliation efficiency in cotton by adjusting hormone synthesis and response related pathways (including auxin, ethylene, and JA) and ROS production at low temperatures.

Clinical efficacy and safety analysis of aumolertinib in real-world treatment of EGFR-mutated advanced non-small-cell lung cancer.

Background: This study aims to determine the efficacy and safety profile of aumolertinib in the real-word treatment setting for advanced non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations. Methods: We retrospectively analyzed the clinical data of 173 EGFR-mutated advanced NSCLC patients who received aumolertinib treatment at Henan Cancer Hospital from April 2020 to December 2022. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier survival curves, while a Cox regression model was used for multifactorial analysis and prognostic factor assessment. Results: Among patients administered first-line aumolertinib (n = 77), the objective remission rate (ORR) of 77.92% was observed, along with a disease control rate (DCR) of 100%. The median progression-free survival (mPFS) was 24.97 months, which did not reach the median overall survival (mOS). The patients treated with aumolertinib after progression on prior EGFR-tyrosine kinase inhibitor (TKI) therapy (n = 96) exhibited an ORR of 46.88%, a DCR of 89.58%, an mPFS of 15.17 months, and an mOS of 21.27 months. First-line treatment multivariate Cox regression analysis demonstrated a statistically significant impact of elevated creatine kinase on PFS (p = 0.016) and a similar significant influence of co-mutation on OS (p = 0.034). Furthermore, subsequent-line treatment multivariate Cox regression analysis showed a statistically significant impact of elevated creatine kinase on median PFS (p = 0.026) and a significant effect on the number of metastatic organs (p = 0.017), co-mutation (p = 0.035), and elevated creatine kinase (p = 0.014) on median OS. Conclusion: Aumolertinib has shown clinical significance and can safely be used in the real-world setting for patients with EGFR mutation-positive NSCLC.

The impact of smart city construction (SCC) on pollution emissions (PE): evidence from China.

Based on panel data from 210 prefecture-level cities in China from 2003 to 2021, this study employs the Time-Varying Differences-in-Differences (Time-Varying DID) approach to systematically examine the impact of smart city construction on pollution emissions and its underlying mechanisms. Additionally, the Propensity Score Matching-Differences-in-Differences method is employed for further validation. The research findings indicate that Smart City Construction (SCC) significantly reduces urban Volume of Sewage Discharge (VSD), sulfur dioxide emissions (SO2), and Emissions of Fumes and Dust (EFD), thereby mitigating pollution emissions (PE) and enhancing environmental quality. Mechanism analysis reveals that SCC achieves these effects through scale effects, structural effects, and technological effects. City heterogeneity analysis shows that provincial capital cities exhibit a stronger suppression effect on pollution emissions compared to non-provincial capital cities. Moreover, cities with lower levels of education attainment demonstrate a stronger ability to curb pollution emissions, while larger cities exhibit a more pronounced impact on mitigating pollution emissions. The marginal contributions of this study mainly consist of three aspects: Firstly, it enriches the literature on environmental impact factors by assessing, for the first time, the influence of SCC on PE. Secondly, a comprehensive approach is employed, integrating VSD, EFD, SO2 data, and economic and pollution data at the city level. Time-Varying DID is used to evaluate the policy effects of SCC. Finally, the study analyzes the impact mechanisms of SCC policy on environmental emissions from various perspectives.

OCTN2- and ATB0,+-targeted nanoemulsions for improving ocular drug delivery.

Traditional eye drops are administered via topical instillation. However, frequent dosing is needed due to their relatively rapid precorneal removal and low ocular bioavailability. To address these issues, stearoyl L-carnitine-modified nanoemulsions (SC-NEs) were fabricated. The physicochemical properties of SC-NEs in terms of size, morphology, zeta potential, encapsulation efficiency, and in vitro drug release behavior were characterized. The cellular uptake and mechanisms of SC-NEs were comprehensively studied in human corneal epithelial cells and the stearoyl L-carnitine ratio in SC-NEs was optimized. The optimized SC-NEs could target the novel organic cation/carnitine transporter 2 (OCTN2) and amino acid transporter B (0 +) (ATB0,+) on the corneal epithelium, which led to superior corneal permeation, ocular surface retention ability, ocular bioavailability. Furthermore, SC-NEs showed excellent in vivo anti-inflammatory efficacy in a rabbit model of endotoxin-induced uveitis. The ocular safety test indicated that the SC-NEs were biocompatible. In general, the current study demonstrated that OCTN2 and ATB0,+-targeted nanoemulsions were promising ophthalmologic drug delivery systems that can improve ocular drug bioavailability and boost the therapeutic effects of drugs for eye diseases.

The Interaction between ADK and SCG10 Regulate the Repair of Nerve Damage.

The cytoskeleton must be remodeled during neurite outgrowth, and Superior Cervical Ganglion 10 (SCG10) plays a critical role in this process by depolymerizing Microtubules (MTs), conferring highly dynamic properties to the MTs. However, the precise mechanism of action of SCG10 in the repair of injured neurons remains largely uncertain. Using transcriptomic identification, we discovered that SCG10 expression was downregulated in neurons after Spinal Cord Injury (SCI). Additionally, through mass spectrometry identification, immunoprecipitation, and pull-down assays, we established that SCG10 could interact with Adenosine Kinase (ADK). Furthermore, we developed an excitotoxicity-induced neural injury model and discovered that ADK suppressed injured neurite re-growth, whereas, through overexpression and small molecule interference experiments, SCG10 enhanced it. Moreover, we discovered ADK to be the upstream of SCG10. More importantly, the application of the ADK inhibitor called 5-Iodotubercidin (5-ITu) was found to significantly enhance the recovery of motor function in mice with SCI. Consequently, our findings suggest that ADK plays a negative regulatory role in the repair of injured neurons. Herein, we propose a molecular interaction model of the SCG10-ADK axis to regulate neuronal recovery.

Comprehensive analysis of the miRNA-mRNA regulatory network involved in spontaneous recovery of an H2O2-induced zebrafish cataract model.

OBJECTIVE: To identify the hub miRNAs and mRNAs contributing to the spontaneous recovery of an H2O2-induced zebrafish cataract model. METHODS: Zebrafishes were divided into three groups, i.e., Group A, which included normal control fish (day 0), and Groups B and C, where fish were injected with 2.5% hydrogen peroxide into the anterior chamber and reared for 14 and 30 days, respectively. Fish eyes were examined by stereomicroscope photography and optical coherence tomography (OCT). RNA profiles of fish lenses were detected by RNA sequencing. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRs) were identified among three groups. The DEGs and DEmiRs, which changed in opposite positions between "B vs. A" and "C vs. B" were defined as ODGs (opposite positions changed DEGs) and ODmiRs (opposite positions changed DEmiRs). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis were carried out by R language. The protein-protein interaction network (PPI) was constructed using STRING. Potential targets of miRNAs were obtained using miRanda. miRNA-mRNA networks were constructed by Cytoscape. RESULTS: The fish lens opacity formed on day 14 and recovered to transparent on day 30 after injection. Compared to group B, 1366 DEGs and 54 DEmiRs were identified in group C. "C vs. B" DEGs were enriched in gene clusters related to development and oxidative phosphorylation. Target genes of DEmiRs were enriched in clusters such as development and cysteine metabolism. Among three groups, 786 ODGs and 27 ODmiRs were identified, and 480 ODGs were predicted as targets of ODmiRs. Target ODGs were enriched in pathways related to methionine metabolism, ubiquitin, sensory system development, and structural constituents of the eye lens. In addition, we established an ODmiRs-ODGs regulation network. CONCLUSION: We identified several hub mRNAs and altered miRNAs in the formation and reversal of zebrafish cataracts. These hub miRNAs/mRNAs could be potential targets for the non-surgical treatment of ARC.

Sintilimab with two cycles of chemotherapy for the treatment of advanced squamous non-small cell lung cancer: a phase 2 clinical trial.

This was a single-arm, multicenter phase 2 clinical trial (ChiCTR1900021726) involving advanced squamous non-small cell lung cancer (sq-NSCLC) patients undergoing 2 cycles of nab-paclitaxel/carboplatin and sintilimab (anti-PD-1), followed by sintilimab maintenance therapy. The median progression-free survival (PFS) was 11.4 months (95% CI: 6.7-18.1), which met the pre-specified primary endpoint. Secondary endpoints included objective response rate reaching 70.5% and a disease control rate of 93.2%, with a median duration of response of 13.6 months [95% CI: 7.0-not evaluable (NE)]. The median overall survival was 27.2 months (95% CI: 20.2-NE) with treatment-related adverse events grades ≥3 occurring in 10.9% of patients. Predefined exploratory endpoints comprised relationships between biomarkers and treatment efficacy, and the association between circulating tumor DNA (ctDNA) dynamics and PFS. Biomarker analysis revealed that the breast cancer gene 2, BMP/Retinoic Acid Inducible Neural Specific 3, F-box/WD repeat-containing protein 7, tyrosine-protein kinase KIT and retinoblastoma 1 abnormalities led to shorter PFS, while ctDNA negative at baseline or clearance at 2 cycles of treatment was associated with longer PFS (18.1 vs. 4.3 months). Taken together, sintilimab in combination with 2 cycles of nab-paclitaxel/carboplatin treatment produced encouraging PFS and better tolerability as first-line treatment for advanced sq-NSCLC.

Automated Impactor for Contusive Spinal Cord Injury Model in Mice.

Spinal cord injury (SCI) due to traumatic injuries such as car accidents and falls is associated with permanent spinal cord dysfunction. Creation of contusion models of spinal cord injury by impacting the spinal cord results in similar pathologies to most spinal cord injuries in clinical practice. Accurate, reproducible, and convenient animal models of spinal cord injury are essential for studying spinal cord injury. We present a novel automated spinal cord injury contusion device for mice, the Guangzhou Jinan University smart spinal cord injury system, that can produce spinal cord injury contusion models with accuracy, reproducibility, and convenience. The system accurately produces models of varying degrees of spinal cord injury via laser distance sensors combined with an automated mobile platform and advanced software. We used this system to create three levels of spinal cord injury mice models, determined their Basso mouse scale (BMS) scores, and performed behavioral as well as staining assays to demonstrate its accuracy and reproducibility. We show each step of the development of the injury models using this device, forming a standardized procedure. This method produces reproducible spinal cord injury contusion mice models and reduces human manipulation factors via convenient handling procedures. The developed animal model is reliable for studying spinal cord injury mechanisms and associated treatment approaches.

DEAD-box helicase 1 inhibited CD8+ T cell antitumor activity by inducing PD-L1 expression in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) does not respond well to current treatments, even immune checkpoint inhibitors. PD-L1 (programmed cell death ligand 1 or CD274 molecule)-mediated immune escape of tumor cells may be a key factor affecting the efficacy of immune checkpoint inhibitor (ICI) therapy. However, the regulatory mechanisms of PD-L1 expression and immune escape require further exploration. Here, we observed that DDX1 (DEAD-box helicase 1) was overexpressed in HCC tissues and associated with poor prognosis in patients with HCC. Additionally, DDX1 expression correlated negatively with CD8+ T cell frequency. DDX1 overexpression significantly increased interferon gamma (IFN-γ)-mediated PD-L1 expression in HCC cell lines. DDX1 overexpression decreased IFN-γ and granzyme B production in CD8+ T cells and inhibited CD8+ T cell cytotoxic function in vitro and in vivo. In conclusion, DDX1 plays an essential role in developing the immune escape microenvironment, rendering it a potential predictor of ICI therapy efficacy in HCC.

14-3-3 protein augments the protein stability of phosphorylated spastin and promotes the recovery of spinal cord injury through its agonist intervention.

Axon regeneration is abortive in the central nervous system following injury. Orchestrating microtubule dynamics has emerged as a promising approach to improve axonal regeneration. The microtubule severing enzyme spastin is essential for axonal development and regeneration through remodeling of microtubule arrangement. To date, however, little is known regarding the mechanisms underlying spastin action in neural regeneration after spinal cord injury. Here, we use glutathione transferase pulldown and immunoprecipitation assays to demonstrate that 14-3-3 interacts with spastin, both in vivo and in vitro, via spastin Ser233 phosphorylation. Moreover, we show that 14-3-3 protects spastin from degradation by inhibiting the ubiquitination pathway and upregulates the spastin-dependent severing ability. Furthermore, the 14-3-3 agonist Fusicoccin (FC-A) promotes neurite outgrowth and regeneration in vitro which needs spastin activation. Western blot and immunofluorescence results revealed that 14-3-3 protein is upregulated in the neuronal compartment after spinal cord injury in vivo. In addition, administration of FC-A not only promotes locomotor recovery, but also nerve regeneration following spinal cord injury in both contusion and lateral hemisection models; however, the application of spastin inhibitor spastazoline successfully reverses these phenomena. Taken together, these results indicate that 14-3-3 is a molecular switch that regulates spastin protein levels, and the small molecule 14-3-3 agonist FC-A effectively mediates the recovery of spinal cord injury in mice which requires spastin participation.