Vpr driving DNA methylation variation of CD4 + T cells in HIV-1 infection.

BACKGROUND: Despite the existence of available therapeutic interventions for HIV-1, this virus remains a significant global threat, leading to substantial morbidity and mortality. Within HIV-1-infected cells, the accessory viral protein r (Vpr) exerts control over diverse biological processes, including cell cycle progression, DNA repair, and apoptosis. The regulation of gene expression through DNA methylation plays a crucial role in physiological processes, exerting its influence without altering the underlying DNA sequence. However, a thorough examination of the impact of Vpr on DNA methylation in human CD4 + T cells has not been conducted. METHODS: In this study, we employed base-resolution whole-genome bisulfite sequencing (WGBS), real-time quantitative RCR and western blot to explore the effect of Vpr on DNA methylation of host cells under HIV-1 infection. RESULTS: We observed that HIV-1 infection leads to elevated levels of global DNA methylation in primary CD4 + T cells. Specifically, Vpr induces significant modifications in DNA methylation patterns, particularly affecting regions within promoters and gene bodies. These alterations notably influence genes related to immune-related pathways and olfactory receptor activity. Moreover, Vpr demonstrates a distinct ability to diminish the levels of methylation in histone genes. CONCLUSIONS: These findings emphasize the significant involvement of Vpr in regulating transcription through the modulation of DNA methylation patterns. Together, the results of this investigation will considerably enhance our understanding of the influence of HIV-1 Vpr on the DNA methylation of host cells, offer potential avenues for the development of more effective treatments.

Advances in performance degradation mechanism and safety assessment of LiFePO4for energy storage.

In the context of 'energy shortage', developing a novel energy-based power system is essential for advancing the current power system towards low-carbon solutions. As the usage duration of lithium-ion batteries for energy storage increases, the nonlinear changes in their aging process pose challenges to accurately assess their performance. This paper focuses on the study LiFeO4(LFP), used for energy storage, and explores their performance degradation mechanisms. Furthermore, it introduces common battery models and data structures and algorithms, which used for predicting the correlation between electrode materials and physical parameters, applying to state of health assessment and thermal warning. This paper also discusses the establishment of digital management system. Compared to conventional battery networks, dynamically reconfigurable battery networks can realize real-time monitoring of lithium-ion batteries, and reduce the probability of fault occurrence to an acceptably low level.

Ripretinib inhibits HIV-1 transcription through modulation of PI3K-AKT-mTOR.

Despite the effectiveness of antiretroviral therapy (ART) in prolonging the lifespan of individuals infected with HIV-1, it does not offer a cure for acquired immunodeficiency syndrome (AIDS). The "block and lock" approach aims to maintain the provirus in a state of extended transcriptional arrest. By employing the "block and lock" strategy, researchers endeavor to impede disease progression by preventing viral rebound for an extended duration following patient stops receiving ART. The crux of this strategy lies in the utilization of latency-promoting agents (LPAs) that are suitable for impeding HIV-1 provirus transcription. However, previously documented LPAs exhibited limited efficacy in primary cells or samples obtained from patients, underscoring the significance of identifying novel LPAs that yield substantial outcomes. In this study, we performed high-throughput screening of FDA-approved compound library in the J-Lat A2 cell line to discover more efficacious LPAs. We discovered ripretinib being an LPA candidate, which was validated and observed to hinder proviral activation in cell models harboring latent infections, as well as CD4+ T cells derived from infected patients. We demonstrated that ripretinib effectively impeded proviral activation through inhibition of the PI3K-AKT-mTOR signaling pathway in the HIV-1 latent cells, thereby suppressing the opening states of cellular chromatin. The results of this research offer a promising drug candidate for the implementation of the "block and lock" strategy in the pursuit of an HIV-1 cure.

In vivo transgenic studies confirm the critical acylation function of LeBAHD56 for shikonin in Lithospermum erythrorhizon.

KEY MESSAGE: LeBAHD56 is preferentially expressed in tissues where shikonin and its derivatives are biosynthesized, and it confers shikonin acylation in vivo. Two WRKY transcriptional factors might regulate LeBAHD56's expression. Shikonin and its derivatives, found in the roots of Lithospermum erythrorhizon, have extensive application in the field of medicine, cosmetics, and other industries. Prior research has demonstrated that LeBAHD1(LeSAT1) is responsible for the biochemical process of shikonin acylation both in vitro and in vivo. However, with the exception of its documented in vitro biochemical function, there is no in vivo genetic evidence supporting the acylation function of the highly homologous gene of LeSAT1, LeBAHD56(LeSAT2), apart from its reported role. Here, we validated the critical acylation function of LeBAHD56 for shikonin using overexpression (OE) and CRISPR/Cas9-based knockout (KO) strategies. The results showed that the OE lines had a significantly higher ratio of acetylshikonin, isobutyrylshikonin or isovalerylshikonin to shikonin than the control. In contrast, the KO lines had a significantly lower ratio of acetylshikonin, isobutyrylshikonin or isovalerylshikonin to shikonin than controls. As for its detailed expression patterns, we found that LeBAHD56 is preferentially expressed in roots and callus cells, which are the biosynthesis sites for shikonin and its derivatives. In addition, we anticipated that a wide range of putative transcription factors might control its transcription and verified the direct binding of two crucial WRKY members to the LeBAHD56 promoter's W-box. Our results not only confirmed the in vivo function of LeBAHD56 in shikonin acylation, but also shed light on its transcriptional regulation.

Ponatinib Represses Latent HIV-1 by Inhibiting AKT-mTOR.

Although antiretroviral therapy (ART) is effective in suppressing viral replication, it does not cure HIV-1 infection due to the presence of the viral latent reservoir. Rather than reactivating the latent viruses, the "block and lock" strategy aims to shift the viral reservoir to a deeper state of transcriptional silencing, thus preventing viral rebound after ART interruption. Although some latency-promoting agents (LPAs) have been reported, none of them have been approved for clinical application due to cytotoxicity and limited efficacy; therefore, it is important to search for novel and effective LPAs. Here, we report an FDA-approved drug, ponatinib, that can broadly repress latent HIV-1 reactivation in different cell models of HIV-1 latency and in primary CD4+ T cells from ART-suppressed individuals ex vivo. Ponatinib does not change the expression of activation or exhaustion markers on primary CD4+ T cells and does not induce severe cytotoxicity and cell dysfunction. Mechanistically, ponatinib suppresses proviral HIV-1 transcription by inhibiting the activation of the AKT-mTOR pathway, which subsequently blocks the interaction between key transcriptional factors and the HIV-1 long terminal repeat (LTR). In summary, we discovered a novel latency-promoting agent, ponatinib, which could have promising significance for future applications of HIV-1 functional cure.

Anterior segment structure changes caused by different luminance light after implantable collamer lens surgery.

BACKGROUNDS: To investigate the changes of anterior eye segment with implantable collamer lens (ICL) under mesopic and photopic conditions. METHOD: Forty-seven eyes of myopic patients who underwent ICL V4c implantation were included. Three months after surgery, the pupil diameter (PD), dynamic vault, ACD (distance from the posterior corneal surface to the anterior lens surface), ACD-ICL (distance from the posterior corneal surface to the anterior ICL surface), and anterior chamber angle parameters were measured using the anterior segment optical coherence tomography (AS-OCT, Carl Zeiss AG, Germany) under completely mesopic (0 lx) and photopic (5290 lx) lighting conditions. RESULTS: Compared with mesopic conditions, a significant decreased vault was detected in photopic conditions (486.7 ± 186.1 µm versus 643.5 ± 191.2 µm, p < 0.001), while the ACD-ICL increased significantly (2.54 ± 0.24 mm versus 2.37 ± 0.23 mm, p < 0.001). The pupil was smaller in photopic condition (2.66 ± 0.23 mm versus 5.62 ± 0.55 mm, p < 0.001). ACD didn't change(3.32 ± 0.24 mm versus 3.31 ± 0.22 mm, p = 0.079). The change of the vault was positively related to the changes of the PD (r2 = 0.301, p = 0.04). There were no statistical difference between the change of vault and the change of ACD-ICL (158.0 ± 58.1 µm versus 165.9 ± 65.3 µm, p = 0.320). CONCLUSION: When exposed to high intensity light after ICL surgery, the pupil constricted, vault decreased, ACA widened and ACD-ICL increased. All these changes were caused by the change of iris not the crystalline lens.

Genome-Wide Comparison and Functional Characterization of HMGR Gene Family Associated with Shikonin Biosynthesis in Lithospermum erythrorhizon.

3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), as the rate-limiting enzyme in the mevalonate pathway, is essential for the biosynthesis of shikonin in Lithospermum erythrorhizon. However, in the absence of sufficient data, the principles of a genome-wide in-depth evolutionary exploration of HMGR family members in plants, as well as key members related to shikonin biosynthesis, remain unidentified. In this study, 124 HMGRs were identified and characterized from 36 representative plants, including L. erythrorhizon. Vascular plants were found to have more HMGR family genes than nonvascular plants. The phylogenetic tree revealed that during lineage and species diversification, the HMGRs evolved independently and intronless LerHMGRs emerged from multi-intron HMGR in land plants. Among them, Pinus tabuliformis and L. erythrorhizon had the most HMGR gene duplications, with 11 LerHMGRs most likely expanded through WGD/segmental and tandem duplications. In seedling roots and M9 cultured cells/hairy roots, where shikonin biosynthesis occurs, LerHMGR1 and LerHMGR2 were expressed significantly more than other genes. The enzymatic activities of LerHMGR1 and LerHMGR2 further supported their roles in catalyzing the conversion of HMG-CoA to mevalonate. Our findings provide insight into the molecular evolutionary properties and function of the HMGR family in plants and a basis for the genetic improvement of efficiently produced secondary metabolites in L. erythrorhizon.

Postmenopausal exogenous hormone therapy and Melanoma risk in women: A systematic review and time-response meta-analysis.

A favourable option to management symptoms during menopausal transition is menopausal hormone therapy (MHT) but relation among MHT and risk of melanoma is controversial. This study aims to identify, analyse and present the evidence surrounding post-menopausal exogenous hormone therapy and the risk for melanoma in women. A systematic searches of database was conducted in PubMed/MEDLINE, Scopus, and Cochrane without time, region, and language restrictions from inception to April 2020. The DerSimonian and Laird random-effects model was used to estimate combined risk ratio (RR) and 95% confidence intervals (CI). Subgroup analysis and time-response analysis was conducted based on the formulation of used hormone and length of hormone therapy. Combined results from fourteen studies that containing 19 arms with 1,164,077 participants which 4273 of them had melanoma cancer showed increase risk of melanoma in the hormone-treated versus control group 1.14 (95% CI 1.05-1.24, I2: 21%). The stronger and significant relationship between MHT and risk of melanoma was in participants who used oestrogen formulation (RR 1.32, 95% CI 1.17-1.49, I2 = 0%). Moreover, a significant non-linear time-response relation between MHT and melanoma was also in initial three years of MHT (Coef1 = 0.2423, p1 < 0.01). This study reveals a significant direct relationship between the MHT and risk of melanoma in postmenopausal women.

Effects of dietary fish meal replacement by fermented moringa (Moringa oleifera Lam.) leaves on growth performance, nonspecific immunity and disease resistance against Aeromonas hydrophila in juvenile gibel carp (Carassius auratus gibelio var. CAS III).

This study was aimed to evaluate the effects of partial replacement of fish meal by fermented moringa leaves (FMLs) on growth performance, serum biochemistry, antioxidant status, nonspecific immunity, and resistance against Aeromonas hydrophila in juvenile gibel carp (Carassius auratus gibelio var. CAS III). Four isonitrogenous and isoenergetic balanced diets, including three FML diets (substituting 20%, 40%, 60% of the fish meal in basal diet, F20, F40 and F60, respectively) and a basal diet (a diet containing 10% fish meal) were used. Each diet was randomly allocated to four fish groups (F20, F40, F60 and control) reared in a recirculating system. After 50 days of the feeding trial, fish were challenged by A. hydrophila. The result revealed that final mean body weight (FBW), weight gain rate (WGR), specific growth rate (SGR), feed efficiency (FE) and survival rate (SR) were significantly increased (P < 0.05) in F20 and F40 groups compared with the control group. Decreased hepatosomatic index (HSI), body crude lipid, serum aspartate transaminase (AST) and serum alanine aminotransferase (ALT) activities, and increased serum alkaline phosphatase (AKP) and serum glutathione peroxidase (GPx) activities were observed in F40 and F60 groups compared with the control and F20 groups. All FMLs-supplemented groups increased (P < 0.05) serum superoxide dismutase (SOD), catalase (CAT) and lysozyme activities, complement component 3 (C3) and serum immunoglobulin M (IgM) concentration, or decreased serum malondialdehyde (MDA) and protein carbonyl (PCC) contents (P < 0.05). After the challenge test, the significant downregulation of toll-like receptors2 (TLR2), tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-8 mRNA transcription levels was observed in spleens of FMLs supplemented groups. Dietary F40 and F60 showed higher (P < 0.05) relative percent survival (RPS) (48.72% and 43.59%, respectively) against A. hydrophila infection than control. These results indicate that, as a dietary fish meal substitute, FMLs enhance the growth, and antioxidant and immune response, and regulate the expression of immune-related genes and increase disease resistance against A. hydrophila via TLR2 pathway in gibel carp, with greatest effects of 40% fish meal substitution.

Transcriptomic analysis of the differentiating ovary of the protogynous ricefield eel Monopterus albus.

BACKGROUND: The ricefield eel is a protogynous hermaphroditic Synbranchiform species that changes sex naturally from female to male, which offers an interesting model for studying gonadal (particularly ovarian) differentiation in vertebrates. In the present study, transcriptome sequencing of the gonad of ricefield eel larvae was performed to explore the molecular mechanisms underlying the ovarian differentiation and development. RESULTS: A total of 301,267,988 clean reads were generated from cDNA libraries of gonadal tissues of ricefield eel larvae at 6, 9, 12, and 20 days post hatching (dph), which contained undifferentiated gonads, differentiating ovaries, ovaries with oogonia, and ovaries with meiotic oocytes, respectively. De-novo assembly of all the clean reads generated a total of 265,896 unigenes with a mean size of 720 bp and a N50 of 1107 bp. RT-qPCR analysis of the developmental expression of 13 gonadal development-related functional genes indicated that RNA-seq data are reliable. Transcriptome data suggest that high expression of female development-related genes and low expression of male development-related genes in the early gonads of ricefield eel larvae participate in the cascade of sex differentiation leading to the final female phenotype. The contrasting expression patterns of genes involved in retinoid acid (RA) synthesis and degradation might result in peak production of RA at 12 dph in the gonad of ricefield eel larvae, and induce molecular events responsible for the initiation of meiosis before the meiotic signs could be observed at 20 dph. In addition, only stra6 but not stra8 could be identified in gonadal transcriptome data of ricefield eel larvae, and the expression pattern of stra6 paralleled those of genes involved in RA synthesis, suggesting that stra6 may be a downstream target of RA and play a role in RA metabolism and/or meiotic initiation in the gonad of ricefield eel larvae. CONCLUSIONS: The present study depicted the first large-scale RNA sequencing of the gonad of ricefield eel larvae, and identified many important functional genes, GO terms and KEGG pathways involved in gonadal development and germ cell meiosis. Results of the present study will facilitate future study on the ovarian differentiation of ricefield eels and other teleosts as well.

Comparative Proteomic and Physiological Analysis Reveals the Variation Mechanisms of Leaf Coloration and Carbon Fixation in a Xantha Mutant of Ginkgo biloba L.

Yellow-green leaf mutants are common in higher plants, and these non-lethal chlorophyll-deficient mutants are ideal materials for research on photosynthesis and plant development. A novel xantha mutant of Ginkgo biloba displaying yellow-colour leaves (YL) and green-colour leaves (GL) was identified in this study. The chlorophyll content of YL was remarkably lower than that in GL. The chloroplast ultrastructure revealed that YL had less dense thylakoid lamellae, a looser structure and fewer starch grains than GL. Analysis of the photosynthetic characteristics revealed that YL had decreased photosynthetic activity with significantly high nonphotochemical quenching. To explain these phenomena, we analysed the proteomic differences in leaves and chloroplasts between YL and GL of ginkgo using two-dimensional gel electrophoresis (2-DE) coupled with MALDI-TOF/TOF MS. In total, 89 differential proteins were successfully identified, 82 of which were assigned functions in nine metabolic pathways and cellular processes. Among them, proteins involved in photosynthesis, carbon fixation in photosynthetic organisms, carbohydrate/energy metabolism, amino acid metabolism, and protein metabolism were greatly enriched, indicating a good correlation between differentially accumulated proteins and physiological changes in leaves. The identifications of these differentially accumulated proteins indicates the presence of a specific different metabolic network in YL and suggests that YL possess slower chloroplast development, weaker photosynthesis, and a less abundant energy supply than GL. These studies provide insights into the mechanism of molecular regulation of leaf colour variation in YL mutants.

[Analysis of twin-arginine translocation system gene homology and transcription in Vibrio species].

OBJECTIVE: To determine the function of twin-arginine translocation system (Tat) and gene cluster in Vibrio strains and to analyze the homology of tat gene cluster among different Vibrio spp. strains based on N16961 and tatABC mutant strains N169-dtat. METHODS: Different serotypes of biotype strains of Vibrio spp. were selected to detect the transcription of 4 genes of Tat transport system and upstream ubi aarF gene and downstream cyt551 gene by the total RNA reverse transcription and homologicity of the gene cluster by sequencing analysis. RESULTS: Our results showed that the 4 genes of tat cluster (tatA, tatB, tatC, and tatE) were intragenic and co-transcribed. We found that ubi aarF gene could be co-transcribed with tatA, tatB, but not with tatC. The electron transport chain and energy metabolism-related genes, cytochrome C551 peroxidase gene, and 4 genes located at upstream of tatABC operon were not transcribed with tatABC. Although the co-transcription between ubi aarF and tatAB was blocked in N169-dtat strain, they were still transcribed separately. Homologous analysis of genes of tat cluster in different types of Vibrio cholerae showed that tat gene cluster was a very conservative. CONCLUSION: The ubi and aarF gene might be co-transcribed with genes of tat cluster in Vibrio cholerae, which and the close relationship showed that they might play a key function in Vibrio cholerae.

[The infection and molecular characteristics of Vibrio parahaemolyticus isolated from intestinal outpatient in two sentinel hospitals in Shanghai, 2010-2012].

OBJECTIVE: To analyze virulence genes and molecular characteristics of Vibrio parahaemolyticus isolated from sporadic cases with diarrhea in tow sentinel hospitals of Shanghai, 2010-2012. METHODS: A total of 2 729 stool samples were collected from two surveillance sentinel hospitals in Shanghai 2010-2012. Vibrio parahaemolyticus strains were isolated and identified from diarrhea out patients using TCBS agar plates and biochemical reactions. Thermostable direct hemolysingene (tdh), thermostable-related hemolysin gene (trh), hemolysin gene (tlh) were detected by multiplex PCR method. Isolates were analyzed by PFGE and MLST. The PFGE profiles were analyzed using BioNumerics software. RESULTS: A total of 30 clinical Vibrio parahaemolyticus strains isolated from 2 729 stool samples. The anually Vibrio parahaemolyticus isolation rate during 2010 to 2012 were 1.1%(11/973), 1.0%(11/1 120) and 1.3%(8/636) respectively. The PCR positive rates of virulence genes tlh, tdh and trh were 100%, 97% and 0 respectively. The Vibrio parahaemolyticus strains were divided into 13 PFGE types (P1-P13)and 3 ST types (ST-189, ST-799, ST-3). Among 13 PFGE types, P4 was the main PFGE type, accounting for 30%(9/30). P9, P10 were accounting for 12% (4/30) respectively, P1, P2, P12, P13 were accounting for 7%(2/30) respectively, the others types were 3%(1/30) respectively. MLST analysis results showed there are three ST types, ST3 was 84%(25/30), ST189 and ST799 were accounting for 13% (4/30) and 3% (1/30) respectively. CONCLUSION: The infection rate of Vibrio parahaemolyticus was not very high from 2010-2012 in Shanghai, all strains were positive for tlh and negative for trh. ST3 was the major type of Vibrio parahaemolyticus.

Does Serum Uric Acid to Creatinine Ratio Predict Mortality Risk in Patients With Heart Failure?

BACKGROUND: Previous studies have established a positive correlation between serum uric acid to creatinine (SUA/Cr) ratio and cardiovascular disease, but the relationship between SUA/Cr ratio and the prognosis of heart failure (HF) remains unknown. This study investigated the potential of SUA/Cr ratio as a prognostic predictor for patients with HF. METHODS: This single-center prospective cohort study enrolled 2,122 patients with HF between March 2013 and June 2017. All patients were divided into 3 groups according to SUA/Cr ratio tertiles and were followed up with until December 31, 2022. The association between SUA/Cr ratio and the prognosis of HF was assessed using the Cox proportional hazards model. RESULTS: The mean (SD) age and mean (SD) SUA/Cr ratio of the study cohort (66% male) were 59.3 (14.7) years and 4.71 (2.09), respectively. During a median follow-up period of 15 months (range, 11-26 months), 390 end-point events were observed. Prognosis analysis revealed that a high SUA/Cr ratio was associated with an increased mortality risk of HF (hazard ratio, 1.62 [95% CI, 1.26-2.09]; P < .001) compared with the SUA/Cr ratio in the lowest tertile. After adjusting for covariates, the hazard ratio for mortality risk of HF was 1.71 (95% CI, 1.23-2.37; P = .001). Subgroup analysis showed that mortality risk increased in direct proportion with the SUA/Cr ratio in female patients, patients with a history of hypertension and ß-blocker use, and patients with UA levels below 428 µmol/L and creatinine levels less than 97 mg/dL. Stratification by age; by history of diabetes, hyperlipidemia, and smoking; and by level of fasting plasma glucose, however, had no obvious effect on the association between SUA/Cr ratio and HF prognosis. Patients with higher SUA/Cr ratios had reduced left ventricular ejection fraction and increased left ventricular end-diastolic diameter. CONCLUSION: A high SUA/Cr ratio was an independent risk factor for the mortality risk of HF.

Physiological and Molecular Response of Liriodendron chinense to Varying Stand Density.

Stand density affects the potentially superior productivity of forest ecosystems directly by regulating the light and nutrient availability of trees. Understanding how stand density influences the growth and development of trees is crucial for supporting forest management in the context of climate change. We focused on Liriodendron chinense in experimental plantations created in 2003, with planting densities ranging from 277 to 10,000 trees per hectare at six plots. The leaf structure and photosynthetic capacity of L. chinense changed significantly under different stand densities, which had a negative impact on their biomass (leaf mass) and nutrient (total carbohydrate content) accumulation. Transcriptional differences were observed among samples from plots with different planting densities. The expression of 1784 genes was negatively dependent on stand density, participating mainly in the biological processes of "circadian rhythm", "carbon metabolism", and "amino acid biosynthesis". Furthermore, we identified a photosynthesis-related module and constructed a gene regulatory network to discover that the transcription factors of MYB and bHLH may have important roles in the transcriptional regulation of photosynthesis biosynthesis by activating or repressing the expression of petA (Litul.15G096200), psbE (Litul.10G033900), and petD (Litul.17G061600) at different stand densities. Our study quantified the impact of stand density on tree growth at physiological and molecular levels. Our observations provide theoretical support for plantation establishment of L. chinense.

Carbon fluxes and water-use efficiency in a Pinus tabuliformis plantation in Northeast China and their relationship to drought.

The impact of extreme weather events on carbon fluxes and water-use efficiency (WUE) in revegetated areas under water-limited conditions is poorly understood. We analyzed changes in carbon fluxes and WUE over three years of eddy-covariance measurements in a Pinus tabuliformis plantation in Northeast China to investigate carbon fluxes and WUE responses to drought events at different time scales. Mean annual net ecosystem exchange (NEE), gross primary production (GPP), and ecosystem respiration (Re) were -368.48, 1042.42, and 673.94 g C m-2, respectively. Drought events increased NEE, as GPP was more sensitive to water stress than Re at different growing stages. Mean annual WUE was 2.46 g C kg-1 H2O, and plant phenology played a key role in WUE responses to drought. Water stress had negative and positive effects on daily WUE at the early and late growing stages, respectively, and daily WUE was generally insensitive to drought at the mid growing stage. A lagged effect existed in the carbon fluxes and WUE dynamics after drought events at various time scales. Water stress at the early growing stage was more important than that at other growing stages on annual carbon sequestration and WUE, as it dominated canopy growth in the current year. The annual mean normalized difference vegetation index controlled interannual variations in carbon fluxes and WUE in the plantation. Our findings contribute to the prediction of possible changes in carbon and water fluxes under climate warming in the afforested areas of Northeast China.

The Efficacy of Paired Opposite Clear Corneal Incisions Correcting Preexisting Low-to-Moderate Astigmatism in Implantable Collamer Lens Surgery.

PURPOSE: To evaluate the efficacy of paired opposite clear corneal incisions (OCCIs) in Implantable Collamer Lens (ICL; STAAR Surgical) implantation surgery for correcting preexisting low-to-moderate astigmatism and observe their influence on corneal aberration. METHODS: This prospective controlled randomized study included 123 eyes: 73 eyes in the ICL surgery group (control group) and 50 eyes in the ICL combined with OCCI group (OCCI group). All patients had corneal astigmatism between 0.50 and 3.00 D. Parameters considered included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refraction, keratometry, slit-lamp biomicroscopy, indirect ophthalmoscopy, corneal topography, and higher order aberrations (HOAs). The Alpins method was used to analyze the correction of astigmatism. The follow-up period lasted for 12 months. RESULTS: Both groups showed a statistically significant improvement in mean UDVA and CDVA after surgery. At 1 and 12 months, the OCCI group had statistically better UDVA than the control group (P = .021 and .01). The OCCI group showed a significant reduction in mean refractive astigmatism from -0.835 ± 0.274 to -0.535 ± 0.353 and -0.450 ± 0.346 D postoperatively (P < .05) after 1 and 12 months. No significant change was observed in the control group (P > .05). The average magnitude of surgically induced astigmatism (SIA) was 0.911 ± 0.442 and 0.811 ± 0.397 D at 1 and 12 months postoperatively, respectively, in the OCCI group, which was slightly lower than the target induced astigmatism. The difference in SIA between the OCCI and control groups was significant by the end of 1 and 12 months postoperatively (P < .0001). The mean correction index was below 1, suggesting an undercorrection effect caused by clear corneal incisions in the opposite direction. HOAs increased in both the control and OCCI groups after surgery (t = 5.668, P < .0001, t = 3.773, P = .0003, respectively), with oblique trefoil only significantly increasing in the OCCI group. CONCLUSIONS: This study demonstrated that OCCIs represent a secure, efficient, reliable, and long-term technique for reducing preexisting low-to-moderate corneal astigmatism during ICL surgery. However, OCCIs did not show any advantageous impact in terms of wavefront aberrations when compared to the traditional single-incision method. The presence of oblique trefoil may be the main contributor to the alteration of HOAs during OCCI surgery. [J Refract Surg. 2024;40(1):e20-e29.].

Astragaloside IV Inhibits Rotenone-Induced α-syn Presentation and the CD4 T-Cell Immune Response.

The increased α-synuclein (α-syn)-dependent activation of CD4 T cells leads to the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN) in Parkinson's disease (PD). Astragaloside IV (AS-IV) protects DA neurons against neuroinflammation. The effects of AS-IV on CD4 T-cell-mediated immune responses in PD remain unknown. Rotenone (ROT) injected unilaterally into the substantia nigra pars compacta (SNc) of rats induced PD. AS-IV (20 mg/kg) was intraperitoneally injected once a day for 14 days. The limb hanging test and rotarod test were performed to evaluate the alteration of behavior at 4 and 6 weeks. Total gastrointestinal transit tests were performed at 4 weeks. Western blotting was used to detect the expression of proinflammatory cytokine proteins. Immunofluorescence staining was conducted to test the expression and localization of major histocompatibility complex class II (MHCII), cleaved caspase-1 and α-syn in astrocytes. Flow cytometry analysis, immunohistochemistry and immunofluorescence staining were used to measure the expression of CD4 T-cell subsets in the SN. The application of AS-IV protected against the loss of DA neurons and behavioral deficits in ROT-induced PD rat models. AS-IV administration inhibited the aggregation of α-syn in DA neurons and the expression of proinflammatory cytokines such as TNF-α, IL-18, IL-6 and IL-1ß. AS-IV decreased the activation of CD4 T cells and three CD4 T-cell subsets: Tfh, Treg and Th1. AS-IV interrupted the ROT-induced interaction between astrocytes and CD4 T cells and the colocalization of MHCII and α-syn in astrocytes. AS-IV inhibited the expression of α-syn in astrocytes and the colocalization of α-syn and cleaved caspase-1 in astrocytes. AS-IV prevents the loss of DA neurons in PD by inhibiting the activation of α-syn-specific CD4 T cells, which is regulated by MHCII-mediated antigen presentation in astrocytes.

Transcription factors Dmrt1a, Foxl2, and Nr5a1a potentially interact to regulate cyp19a1a transcription in ovarian follicles of ricefield eel (Monopterus albus).

Aromatase (encoded by Cyp19a1) in the ovarian follicular cells catalyzes the production of estradiol from testosterone, which plays important roles in the ovarian development of vertebrates. In the present study, the interaction of Dmrt1, Foxl2, and Nr5a1a on the regulation of cyp19a1a transcription in ovarian follicles was examined in a teleost, the ricefield eel Monopterus albus. The expression of dmrt1a, foxl2, and nr5a1a was detected in ovarian follicular cells together with cyp19a1a at the mRNA and/or protein levels. Sequence analysis identified one conserved Foxo binding site in the proximal promoter region of ricefield eel cyp19a1a. Transient transfection assay showed that Foxl2 may bind to the conserved Foxo site to activate cyp19a1a transcription and act synergistically with Nr5a1a. Mutation of either the conserved Nr5a1 site or Foxo site abolished or significantly decreased the synergistic effects of Nr5a1a and Foxl2 on cyp19a1a transcription. The sequence between Region III and I-box of Nr5a1a was critical to this synergistic effect. Dmrt1a modulated the Foxl2- and Nr5a1a-induced activation of cyp19a1a transcription and their synergistic effects in a biphasic manner, with inhibitory roles observed at lower doses (10-50 ng) but release of the inhibition or even potentiating effects observed at higher doses (100-200 ng). Collectively, data of the present study suggest that the interaction of Dmrt1a, Foxl2, and Nr5a1a in the ovarian follicular cells may facilitate the adequate expression of cyp19a1a and the production of estradiol, and contribute to the development and maturation of ovarian follicles in ricefield eels and other vertebrates as well.

Surface energy partitioning and evapotranspiration in a Pinus tabuliformis plantation in Northeast China.

Examining the land-atmosphere interaction in vegetation rehabilitation areas is important for better understanding of land surface processes affected by human activities. In this study, energy flux observations were used to investigate surface energy partitioning and evapotranspiration (ET) in a Pinus tabuliformis plantation in Northeast China in 2020 and 2021. The sensible heat flux (H) was the dominant component of Rn, and the ratio of H to the latent heat flux was higher than 1 at all growth stages. The two most important factors influencing the midday evaporative fraction and daily ET were the normalized difference vegetation index (NDVI) and soil water content at 10 cm depth (SWC10). Cumulative precipitation (P) minus ET was 62.83 and 239.90 mm in 2020 (annual P of 435.2 mm) and 2021 (annual P of 632.8 mm), respectively. The midday Priestley-Taylor coefficient (α), surface conductance (gs), and decoupling coefficient increased gradually from the onset of the mid-growing stage and decreased from the later growing stage. Midday α and gs increased with NDVI and SWC10 increasing until the NDVI (0.5) and SWC10 (0.17 mm3 mm-3) thresholds were reached, respectively. Midday α and gs were significantly influenced by vapor pressure deficit below 3 kPa, and the threshold value of midday gs was approximately 12 mm s-1. In conclusion, this Pinus tabuliformis plantation regulated surface energy partitioning properly, and left a part of P for surface runoff and groundwater recharge in the semiarid region of Northeast China.