The generation and characterization of a transgenic zebrafish line with lens-specific Cre expression.

Purpose: Danio rerio zebrafish constitute a popular model for studying lens development and congenital cataracts. However, the specific deletion of a gene with a Cre/LoxP system in the zebrafish lens is unavailable because of the lack of a lens-Cre-transgenic zebrafish. This study aimed to generate a transgenic zebrafish line in which Cre recombinase was specifically expressed in the lens. Methods: The pTol2 cryaa:Cre-polyA-cryaa:EGFP (enhanced green fluorescent protein) plasmid was constructed and co-injected with Tol2-transposase into one-to-two-cell-stage wild-type (WT) zebrafish embryos. Whole-mount in situ hybridization (ISH), tissue section, hematoxylin and eosin staining, a Western blot, a split-lamp observation, and a grid transmission assay were used to analyze the Cre expression, lens structure, and lens transparency of the transgenic zebrafish. Results: In this study, we generated a transgenic zebrafish line, zTg(cryaa:Cre-cryaa:EGFP), in which Cre recombinase and EGFP were driven by the lens-specific cryaa promoter. zTg(cryaa:Cre-cryaa:EGFP) began to express Cre and EGFP specifically in the lens at the 22 hpf stage, and this ectopic Cre could efficiently and specifically delete the red fluorescent protein (RFP) signal from the lens when zTg(cryaa:Cre-cryaa:EGFP) embryos were injected with the loxP-flanked RFP plasmid. The overexpression of Cre and EGFP did not impair zebrafish development or lens transparency. Accordingly, this zTg(cryaa:Cre-cryaa:EGFP) zebrafish line is a useful tool for gene editing, specifically with zebrafish lenses. Conclusions: We established a zTg(cryaa:Cre-cryaa:EGFP) zebrafish line that can specifically express an active Cre recombinase in lens tissues. This transgenic zebrafish line can be used as a tool to specifically manipulate a gene in zebrafish lenses.

The downregulation of HSP90-controlled CRALBP expression is associated with age-related vision attenuation.

The dysfunction of CRALBP, a key regulator of the visual cycle, is associated with retinitis punctata albescens characterized by night vision loss and retinal degeneration. In this paper, we find that the expression of CRALBP is regulated by heat shock protein 90 (HSP90). Inhibition of HSP90α or HSP90ß expression by using the CRISPR-Cas9 technology downregulates CRALBP's mRNA and protein expression in ARPE-19 cells by triggering the degradation of transcription factor SP1 in the ubiquitin-proteasome pathway. SP1 can bind to CRALBP's promoter, and inhibition of SP1 by its inhibitor plicamycin or siRNA downregulates CRALBP's mRNA expression. In the zebrafish, inhibition of HSP90 by the intraperitoneal injection of IPI504 reduces the thickness of the retinal outer nuclear layer and Rlbp1b mRNA expression. Interestingly, the expression of HSP90, SP1, and CRALBP is correlatedly downregulated in the senescent ARPE-19 and Pig primary RPE cells in vitro and in the aged zebrafish and mouse retinal tissues in vivo. The aged mice exhibit the low night adaption activity. Taken together, these data indicate that the HSP90-SP1 is a novel regulatory axis of CRALBP transcriptional expression in RPE cells. The age-mediated downregulation of the HSP90-SP1-CRALBP axis is a potential etiology for the night vision reduction in senior people.

Diagnostic value and role of serum miR-15a-5p in patients with schizophrenia.

BACKGROUND: More and more studies have confirmed that the heredity plays an important role in mental disorders, especially microRNA. The objective of this research was to explore the level of miR-15a-5p in patients with schizophrenia (SZ), and to evaluate the feasibility of this miRNA as a diagnostic marker of SZ. METHODS: The serum level of miR-15a-5p in patients with SZ and healthy people was detected by RT-qPCR. ROC curve was established to evaluate the clinical diagnostic significance of miR-15a-5p in SZ. Pearson correlation coefficient was used to evaluate the correlation between miR-15a-5p level and PANSS score. Logistic regression was used to assess the risk factors of SZ. A rat model of SZ was established, and the effects of miR-15a-5p on the behavior of SZ rats were observed through water maze test and open field test. RESULTS: The serum level of miR-15a-5p in patients with SZ was significantly increased, and ROC analysis revealed that miR-15a-5p had clinical diagnostic value in SZ. High level of miR-15a-5p was positively correlated with the positive symptom, negative symptom and general psychopathology subscore of patients. Logistic regression results showed that miR-15a-5p was a risk factor affecting the occurrence of SZ. Animal studies showed that the serum level of miR-15a-5p was elevated in the SZ rats, and inhibiting the expression of miR-15a-5p has a positive effect on improving the cognitive function and anxiety behavior of SZ rats. CONCLUSIONS: Serum miR-15a-5p is a risk factor for SZ, which is of great significance for the diagnosis of SZ.

SARS-COV-2 spike protein promotes RPE cell senescence via the ROS/P53/P21 pathway.

SARS-Cov-2 infection, which has caused the COVID-19 global pandemic, triggers cellular senescence. In this study, we investigate the role of the SARS-COV-2 spike protein (S-protein) in regulating the senescence of RPE cells. The results showed that administration or overexpression of S-protein in ARPE-19 decreased cell proliferation with cell cycle arrest at the G1 phase. S-protein increased SA-ß-Gal positive ARPE-19 cells with high expression of P53 and P21, senescence-associated inflammatory factors (e.g., IL-1ß, IL-6, IL-8, ICAM, and VEGF), and ROS. Elimination of ROS by N-acetyl cysteine (NAC) or knocking down p21 by siRNA diminished S-protein-induced ARPE cell senescence. Both administrated and overexpressed S-protein colocalize with the ER and upregulate ER-stress-associated BIP, CHOP, ATF3, and ATF6 expression. S-protein induced P65 protein nuclear translocation. Inhibition of NF-κB by bay-11-7082 reduced S-protein-mediated expression of senescence-associated factors. Moreover, the intravitreal injection of S-protein upregulates senescence-associated inflammatory factors in the zebrafish retina. In conclusions, the S-protein of SARS-Cov-2 induces cellular senescence of ARPE-19 cells in vitro and the expression of senescence-associated cytokines in zebrafish retina in vivo likely by activating ER stress, ROS, and NF-κb. These results may uncover a potential association between SARS-cov-2 infection and development of AMD.

MicroRNA-124-3p attenuates the development of nerve injury-induced neuropathic pain by targeting early growth response 1 in the dorsal root ganglia and spinal dorsal horn.

Emerging evidence indicates the early growth response 1 (Egr1) plays an important role in the pathogenesis of chronic pain. However, the regulation of Egr1 expression in the DRG and spinal cord in neuropathic pain remains unclear. In the current study, the neuropathic pain was conducted by lumber 5 spinal nerve ligation (SNL) in rats. The role of miR-124-3p in Egr1 expression was examined. Our results showed that the SNL led to a significant increase in the expression of Egr1 mRNA and protein in the DRG and dorsal horn. This increased expression of Egr1 correlated with a reduction of miR-124-3p in the same region. Prior i.t. injection of Egr1 decoy AYX1 inhibited the expression of Egr1 and attenuated the neuropathic pain-like hypersensitivity following SNL. The dual-luciferase reporter assay revealed the luciferase activity of the Egr1 3'-UTR plasmid was inhibited by the miR-124-3p agomir. But this inhibition was completely reversed in the mutant 3'-UTR Egr1 group. In vivo, the SNL-induced behavioral signs of neuropathic pain and the increases in Egr1 mRNA and protein in the DRG and dorsal horn were prevented by prior to i.t. injection of miR-124-3p agomir. While, i.t. injection of miR-124-3p antagomir in naïve rats resulted in mechanical allodynia and thermal hyperalgesia and an overexpression of Egr1 in the DRG and dorsal horn. Together, our results suggest that the miR-124-3p-regulated Egr1 expression in the DRG and dorsal horn contributes to the development of neuropathic pain. Targeting miR-124-3p might be a promising therapeutic strategy in the treatment of chronic pain.

KDM6B epigenetically regulated-interleukin-6 expression in the dorsal root ganglia and spinal dorsal horn contributes to the development and maintenance of neuropathic pain following peripheral nerve injury in male rats.

The lysine specific demethylase 6B (KDM6B) has been implicated as a coregulator in the expression of proinflammatory mediators, and in the pathogenesis of inflammatory and arthritic pain. However, the role of KDM6B in neuropathic pain has yet to be studied. In the current study, the neuropathic pain was determined by assessing the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) following lumbar 5 spinal nerve ligation (SNL) in male rats. Immunohistochemistry, Western blotting, qRT-PCR, and chromatin immunoprecipitation (ChIP)-PCR assays were performed to investigate the underlying mechanisms. Our results showed that SNL led to a significant increase in KDM6B mRNA and protein in the ipsilateral L4/5 dorsal root ganglia (DRG) and spinal dorsal horn; and this increase correlated a markedly reduction in the level of H3K27me3 methylation in the same tissue. Double immunofluorescence staining revealed that the KDM6B expressed in myelinated A- and unmyelinated C-fibers in the DRG; and located in neuronal cells, astrocytes, and microglia in the dorsal horn. Behavioral data showed that SNL-induced mechanical allodynia and thermal hyperalgesia were impaired by the treatment of prior to i.t. injection of GSK-J4, a specific inhibitor of KDM6B, or KDM6B siRNA. Both microinjection of AAV2-EGFP-KDM6B shRNA in the lumbar 5 dorsal horn and sciatic nerve, separately, alleviated the neuropathic pain following SNL. The established neuropathic pain was also partially attenuated by repeat i.t. injections of GSK-J4 or KDM6B siRNA, started on day 7 after SNL. SNL also resulted in a remarkable increased expression of interleukin-6 (IL-6) in the DRG and dorsal horn. But this increase was dramatically inhibited by i.t. injection of GSK-J4 and KDM6B siRNA; and suppressed by prior to microinjection of AAV2-EGFP-KDM6B shRNA in the dorsal horn and sciatic nerve. Results of ChIP-PCR assay showed that SNL-induced enhanced binding of STAT3 with IL-6 promoter was inhibited by prior to i.t. injection of GSK-J4. Meanwhile, the level of H3K27me3 methylation was also decreased by the treatment. Together, our results indicate that SNL-induced upregulation of KDM6B via demethylating H3K27me3 facilitates the binding of STAT3 with IL-6 promoter, and subsequently mediated-increase in the expression of IL-6 in the DRG and dorsal horn contributes to the development and maintenance of neuropathic pain. Targeting KDM6B might a promising therapeutic strategy to treatment of chronic pain.

PARP-1-regulated TNF-α expression in the dorsal root ganglia and spinal dorsal horn contributes to the pathogenesis of neuropathic pain in rats.

Emerging evidence has implicated poly-(ADP-ribose) polymerase 1 (PARP-1), a transcriptional coregulator, in a variety of inflammatory diseases. In the current study, the role of PARP-1 in neuropathic pain and the underlying mechanisms were investigated. Neuropathic pain was determined by assessing the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) following lumbar 5 spinal nerve ligation (SNL) in male rates. Western blotting, qRT-PCR, immunohistochemistry, chromatin immunoprecipitation (ChIP), and Co-IP assays were performed to elucidate the mechanisms. The results showed that SNL resulted in a significant increase in the expression and activation of PARP-1 in the ipsilateral L4/5 dorsal root ganglia (DRG) and spinal dorsal horn, which occurred on day one, reached peak on day 7, and persisted more than 2 weeks after surgery. Double immunofluorescence staining revealed that PARP-1 was expressed exclusively in DRG A-type and C-type neurons. In the spinal cord, PARP-1 mainly colocalized with the neuronal marker NeuN and the astrocytic marker GFAP specifically in the superficial lamina. Prior intrathecal (i.t.) injection of PJ-34, a PARPs inhibitor, or Tiq-A, a specific PARP-1 inhibitor, dose-dependently prevented the reductions in PWT and PWL following SNL. Established neuropathic pain-like hypersensitivity was also attenuated with i.t. injection of PJ-34 and Tiq-A starting on day 7 following SNL, a timepoint at which neuropathic pain was fully established. SNL-induced mechanical allodynia and thermal hyperalgesia were also alleviated by i.t. injection of PARP-1 siRNA following a reduction in PARP-1 expression in the dorsal horn. Moreover, the SNL-induced increases in TNF-α protein and mRNA in the dorsal horn and DRG were dramatically suppressed by i.t. injection of Tiq-A or PARP-1 siRNA. The i.t. lipopolysaccharide (LPS)-induced increase in the production of TNF-α in the dorsal horn was also inhibited by prior to i.t. injection of PARP-1 siRNA. Results of ChIP assay showed that SNL-induced PARP-1 activation promoted the binding of NF-κB p65 with the TNF-α promoter in the dorsal horn and that PARP-1 inhibition reduced this binding and suppressed TNF-α expression. Co-IP assay revealed that SNL caused a significant increase in the level of histone H1 poly(ADP)-ribosylation. Together, these results indicate that PARP-1-regulated TNF-α expression in the DRG and spinal dorsal horn following SNL contributes to the development and maintenance of neuropathic pain. Targeting PARP-1 might be a promising therapeutic strategy for the treatment of the chronic pain.

Motion-Blur-Free High-Speed Video Shooting Using a Resonant Mirror.

This study proposes a novel concept of actuator-driven frame-by-frame intermittent tracking for motion-blur-free video shooting of fast-moving objects. The camera frame and shutter timings are controlled for motion blur reduction in synchronization with a free-vibration-type actuator vibrating with a large amplitude at hundreds of hertz so that motion blur can be significantly reduced in free-viewpoint high-frame-rate video shooting for fast-moving objects by deriving the maximum performance of the actuator. We develop a prototype of a motion-blur-free video shooting system by implementing our frame-by-frame intermittent tracking algorithm on a high-speed video camera system with a resonant mirror vibrating at 750 Hz. It can capture 1024 × 1024 images of fast-moving objects at 750 fps with an exposure time of 0.33 ms without motion blur. Several experimental results for fast-moving objects verify that our proposed method can reduce image degradation from motion blur without decreasing the camera exposure time.

Engineered TAL Effector modulators for the large-scale gain-of-function screening.

Recent effective use of TAL Effectors (TALEs) has provided an important approach to the design and synthesis of sequence-specific DNA-binding proteins. However, it is still a challenging task to design and manufacture effective TALE modulators because of the limited knowledge of TALE-DNA interactions. Here we synthesized more than 200 TALE modulators and identified two determining factors of transcription activity in vivo: chromatin accessibility and the distance from the transcription start site. The implementation of these modulators in a gain-of-function screen was successfully demonstrated for four cell lines in migration/invasion assays and thus has broad relevance in this field. Furthermore, a novel TALE-TALE modulator was developed to transcriptionally inhibit target genes. Together, these findings underscore the huge potential of these TALE modulators in the study of gene function, reprogramming of cellular behaviors, and even clinical investigation.

Pixel-Level and Robust Vibration Source Sensing in High-Frame-Rate Video Analysis.

We investigate the effect of appearance variations on the detectability of vibration feature extraction with pixel-level digital filters for high-frame-rate videos. In particular, we consider robust vibrating object tracking, which is clearly different from conventional appearance-based object tracking with spatial pattern recognition in a high-quality image region of a certain size. For 512 × 512 videos of a rotating fan located at different positions and orientations and captured at 2000 frames per second with different lens settings, we verify how many pixels are extracted as vibrating regions with pixel-level digital filters. The effectiveness of dynamics-based vibration features is demonstrated by examining the robustness against changes in aperture size and the focal condition of the camera lens, the apparent size and orientation of the object being tracked, and its rotational frequency, as well as complexities and movements of background scenes. Tracking experiments for a flying multicopter with rotating propellers are also described to verify the robustness of localization under complex imaging conditions in outside scenarios.

Advances in Research on Protein Arginine Methyltransferase 2: Functions and Diseases.

Protein arginine methylation stands as a prevalent post-translational modification process, exerting vital roles in cellular signal transduction, gene expression, and cell cycle regulation. Amidst the protein arginine methyltransferase (PRMT) family, PRMT2 stands as a less explored constituent. Nonetheless, its regulatory roles in transcriptional regulation, post-transcriptional modification, methylation activity regulation, immunoregulation, and developmental regulation have garnered attention. These capabilities enable PRMT2 to exert pivotal regulatory functions in certain malignancies, metabolic disorders, inflammatory diseases, and atherosclerosis. In this review, we highlight the structure and functions of PRMT2, emphasizing its association with diseases. We also discuss PRMT2 inhibitors and explore the potential for therapeutic targeting.

Investigation of LncRNA PVT1 and MiR-21-5p Expression as Promising Novel Biomarkers for Autism Spectrum Disorder.

The characteristics of ncRNA in children with autism spectrum disorder (ASD) were observed to disclose a theoretical basis for further research on molecular markers for early warning of ASD. Children with ASD and normal control children were recruited to collect peripheral blood RNA samples. The concentration of PVT1 and miR-21-5p was quantitatively analyzed by qRT-PCR. Pearson correlation coefficient method was used to evaluate the link between PVT1 level and miR-21-5p level of the children. Receiver operating characteristic (ROC) curves were applied to reckon the predictive value of PVT1, miR-21-5p, and their combination in ASD. The interconnection of PVT1 with miR-21-5p was represented by luciferase reporter assay. The targeted genes of miR-21-5p were predicted. The enrichment and protein interaction analysis of these genes was carried out to find the important core genes and analyze their value in ASD. In the disease group, the level of PVT1 was downregulated, while the content of miR-21-5p was upregulated. The expression level of serum miR-21-5p was negatively correlated with the level of PVT1. Luciferase reporter gene assay documented that PVT1 directly targeted miR-21-5p. ROC curve showed that PVT1, miR-21-5p, and their combination showed clinical value for disease diagnosis. The functional enrichment analysis showed that the targets of miR-21-5p participated in ASD by regulating related functions and pathways. Reduced expression of PVT1 and raised miR-21-5p were good diagnostic markers for ASD, which would provide a basis for effective prevention, early diagnosis, and early intervention of ASD.

Case report: Urothelial injury in a female with breast cancer: a rare adverse event after the combination of paclitaxel and trastuzumab.

Several breast cancer (BC) patients showed urinary tract infection after adjuvant trastuzumab plus paclitaxel, but no case of urothelial injury has been reported. In this case, we report a 47-year-old female patient with stage I invasive ductal carcinoma in the left breast presenting with urothelial injury after the combination of trastuzumab and paclitaxel. Initially, the patient was highly suspected of having urinary tract infection as she showed abdominal and low back pain, as well as urinary irritation symptoms and hematuria. Unfortunately, the conditions were not attenuated after anti-infection therapy. Contrast-enhanced CT showed extensive exudation and edema in the bilateral renal pelvis, ureter, and bladder, together with dilatation and effusion in the renal pelvis and ureter. Cystoscopy showed extensive congestion, edema, and erosion in the bladder epithelium. Pathological analysis demonstrated slight thinning or even loss in the uroepithelial cell layer and interstitial congestion. In addition, there was growth arrest in the epithelial cells. Immunohistochemistry indicated HER2 expression in the urothelial cells. Finally, the patient was diagnosed with urothelial injury after combination of paclitaxel and trastuzumab. The symptoms were spontaneously cured with no administration of any antibiotics in the 3-month follow-up.

Are the Costimulatory Molecule Gene Polymorphisms (CTLA-4) Associated With Infection in Organ Transplantation? A Meta-Analysis.

Organ transplantation has been linked to certain gene polymorphisms. The effect of gene polymorphisms-associated organ transplantation gene on infection, on the other hand, is yet unknown. The research studying the link between the CTLA-4 rs5742909, rs733618, rs4553808, rs231775, and polymorphisms of the organ transplantation gene and infection were found in PubMed, Web of Science, Scopus, and Embase, and the published articles from 2012 to 2020 were gathered. For the best estimation of the intended results, a random-effects model was used in this meta-analysis. In this study, 1,567 studies were initially included and 9 eligible studies were eligible for further analyses. A significant correlation between CTLA4+49 [A/G-231775 odds ratio (OR) = 077, 0.59-0.95] and CTLA4 [rs5742909TT OR: 0.09, 0.27-0.45] gene polymorphism with infection in organ transplantation was observed. Also, no significant association was found between other CTLA4 gene polymorphisms with infection in organ transplantation. Further studies involving gene-gene and gene-diet interactions should be conducted to investigate this association with infection.

The relationship between sleep duration and activities of daily living (ADL) disability in the Chinese oldest-old: A cross-sectional study.

Objective: To investigate the relationship between sleep duration and activities of daily living (ADL) disability, and to explore the optimal sleep duration among oldest-old Chinese individuals. Methods: In this cross-sectional study, 1,798 participants (73.2% female) were recruited from Dongxing and Shanglin in Guangxi Zhuang Autonomous Region, China in 2019. The restricted cubic spline function was used to assess the dose-response relationship between sleep duration and ADL disability, and the odds ratios (ORs) of the associations were estimated by logistic regression models. Results: The overall prevalence of ADL disability was 63% (64% in females and 58% in males). The prevalence was 71% in the Han population (72% in females and 68% in males), 60% in the Zhuang population (62% in females and 54% in males) and 53% in other ethnic population (53% in females and 53% in males). A nonlinear relationship between sleep duration and ADL disability was observed. Sleep duration of 8-10 hours was associated with the lowest risk of ADL disability. Sleep duration (≥12 hours) was associated with the risk of ADL disability among the oldest-old individuals after adjusting for confounding factors (OR = 1.47, 95% CI [1.02, 2.10], p < 0.05). Conclusion: Sleep duration more than 12 hours may be associated with an increased risk of ADL disability in the oldest-old individuals, and the optimal sleep duration among this population could be 8-10 h.

Exploration for the reference interval of C-reactive protein in the Chinese longevity people over 90 years of age.

BACKGROUND: Older individuals tend to develop chronic inflammation. As a commonly used nonspecific inflammatory marker, C-reactive protein (CRP) can predict metabolic syndrome, cardiovascular diseases, etc. However, little is known about CRP levels in longevity people. OBJECTIVES: Investigate the distribution and correlates of CRP and provide a reference for the establishment of normal interval values in Chinese longevity people over 90 years of age. METHODS: We performed a correlation analysis to evaluate the correlation between CRP levels and longevity based on the basic demographic characteristics, anthropometric measurements and blood data of 4,418 participants in the 2015 China Health and Retirement Longitudinal Study and 636 participants in an ongoing longitudinal study of natural longevity people in Guangxi. On this basis, the CRP reference interval for longevity was explored. RESULTS: The CRP concentration was significantly different among the three age groups, with a median of 3.80 mg/L for those older than 90 years, which was significantly higher than that for those aged 45-64 years (median 1.20 mg/L, p < 0.001) and 65-89 years (median 1.30 mg/L, p < 0.001). Body mass index, waist circumference, the waist-to-height ratio, systolic blood pressure, diastolic blood pressure, and fasting and postprandial blood glucose, triglyceride, total cholesterol and low-density lipoprotein cholesterol levels were positively correlated with CRP levels, while fasting high-density lipoprotein cholesterol was negatively correlated with CRP levels. The CRP reference interval (RI) value in longevity people was 0.25-9.22 mg/L. CONCLUSION: The concentrations of CRP increased with advancing age, and the CRP reference interval was different between older and younger adults.

3-(2,4-Dichloro-phen-yl)-5-(4-fluoro-phen-yl)-2-methyl-7-(trifluoro-meth-yl)pyrazolo-[1,5-a]pyrimidine.

In the title compound, C(20)H(11)Cl(2)F(4)N(3), the central pyrazolo-[1,5-a]pyrimidine unit is almost planar [the mean deviation from the best least-square plane through the nine atoms is 0.006 (2) Å]. The fluoro-benzene ring is rotated out of this plane by 10.3 (3)°, whereas the dichloro-benzene ring is rotated by 46.2 (3)°. The crystal packing is dominated by Cl⋯Cl inter-actions of 3.475 (3) Šand van der Waals inter-actions.

An integrated chip for the high-throughput synthesis of transcription activator-like effectors.

A TALE of two assays: Transcription activator-like effectors (TALEs) are programmable proteins that can specifically recognize a DNA sequence. Previous strategies for the synthesis of TALEs were complicated and time-consuming. The solid-phase synthesis strategy demonstrated here allows quick and simple purification of the ligation product.

The Relationship Between Systemic Immune Inflammatory Index and Prognosis of Patients With Non-Small Cell Lung Cancer: A Meta-Analysis and Systematic Review.

Background: The relationship between systemic immune inflammation index (SII) and the prognosis of cancer has always been a subject of intense interest. However, the prognostic value of SII in non-small cell lung cancer (NSCLC) patients remains a controversial topic. Objective: To evaluate the effect of SII index on prognosis of NSCLC. Methods: We conducted a comprehensive search of PubMed, EMBASE, and the Cochrane Library databases to determine correlation between SII index, clinicopathological features, overall survival (OS), and progression-free survival (PFS). Odds ratio (ORs) and 95% confidence interval (CIs) were used to assess the connection between SII and clinicopathological parameters, and HRs and 95% CIs were used to assess the connection between SII and survival. Results: Seventeen studies with 8,877 cases were included in the analysis. Compared with NSCLC patients with low SII level, patients with NSCLC with high SII level had a poor OS (HR = 1.75, 95% CI, 1.50-2.00; P < 0.001) and had a poor PFS (HR = 1.61, 95% CI, 1.25-1.96; P < 0.001). In addition, patients with higher pathological stage (II-III) had higher SII levels (OR = 2.32, 95% CI, 2.06-2.62; P < 0.001). Conclusions: The SII index is a promising prognostic biomarker for NSCLC and may help clinicians choose appropriate NSCLC treatments.

An LC-MS-based metabolomic approach provides insights into the metabolite profiles of Ginkgo biloba L. at different developmental stages and in various organs.

Ginkgo (Ginkgo biloba L.) is a tree valued for the high medicinal and nutritional value of its leaves and seeds. However, the metabolite profiles of ginkgo leaves and seeds and their changes during development have not been comprehensively analyzed, which hinders improvements in the utilization of ginkgo. A comprehensive and systematic untargeted LC-MS metabolomics analysis of the metabolites in ginkgo leaves (male and female) and seeds at two developmental stages identified 8146 known metabolites, which mainly included lipids and lipid-like molecules, phenylpropanoids and polyketides, organoheterocyclic compounds, organic acids and derivatives, organic oxygen compounds, and benzenoids. Some of the identified metabolites have known healthcare and food value, and some of the others are newly discovered metabolites with potential for new drug development. The small number of differential Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between leaves of male and female gingko trees indicated that the developmental stage affected the metabolic pathways more significantly than sex. Among the flavonoid constituents of ginkgo, 653 flavonoid metabolites were identified, and these included some new flavonoid components, which confirmed that the developmental stage is a critical factor in secondary metabolite variations. This study illuminated the metabolites and medicinal and edible values of ginkgo leaves and seeds at different developmental stages and thus supports further effective utilization of ginkgo leaves and seeds.