Photothermal Iron-Based Riboflavin Microneedles for the Treatment of Bacterial Keratitis via Ion Therapy and Immunomodulation.

Bacterial biofilm formation protects bacteria from antibiotics and the immune system, excessive inflammation further complicates treatment. Here, iron-based metal-organic framework (MIL-101)-loaded riboflavin nanoparticles are designed for the therapeutic challenge of biofilm infection and hyperinflammation in bacterial keratitis. Specifically, MIL-101 produces a thermal effect under exogenous near-infrared light irradiation, which synergizes with ferroptosis-like bacterial death induced by iron ions to exert an effective biofilm infection eradication effect. On the other hand, the disintegration of MIL-101 sustains the release of riboflavin, which inhibits the pro-inflammatory response of macrophage over-activation by modulating their phenotypic switch. In addition, to solve the problems of short residence time, poor permeability, and low bioavailability of corneal medication, the MR@MN microneedle patch is further prepared by loading nanoparticles into SilMA hydrogel, which ultimately achieves painless, transepithelial, and highly efficient drug delivery. In vivo and ex vivo experiments demonstrate the effectiveness of this approach in eliminating bacterial infection and promoting corneal healing. Therefore, the MRMN patch, acting as an ocular drug delivery system with the ability of rapid corneal healing, promises a cost-effective solution for the treatment of bacterial keratitis, which may also lead to a new approach for treating bacterial keratitis in clinics.

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.

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.

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.

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.

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.

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.

[Responses of tree growth and intrinsic water-use efficiency of Robinia pseudoacacia to climate factors]. / åˆºæ§ç”Ÿé•¿å’Œå† åœ¨æ°´åˆ†åˆ©ç”¨æ•ˆçŽ‡å¯¹æ°”å€™å› å­çš„å“åº”.

We investigated tree growth in Robinia pseudoacacia plantations at Ansai in Shaanxi Province and at Ji-xian in Shanxi Province by comparing the tree-ring width, basal area increase (BAI), δ13C value, intrinsic water-use efficiency (iWUE), and stomatal regulation. We quantified the responses of tree growth and iWUE to climatic factors at each site. The tree-ring width at Ansai and Jixian decreased with stand age, whereas the BAI at Ansai increased, and that at Jixian decreased after the BAI peaked. The δ13C value and iWUE of trees at Jixian were higher than those at Ansai. The iWUE of trees at both sites was similar to the constant intercellular CO2 concentration/atmospheric CO2 concentration (Ci/Ca) scenario, indicating that the Ci of trees was elevated with increasing Ca, while the stomata remained open. The BAI at Ansai was significantly positively correlated with highest temperature in May, relative humidity in June, precipitation in August, relative humidity in September, and standardized precipitation evapotranspiration index (SPEI) in September and October of current year, but negatively correlated with temperature in June. The BAI at Jixian was significantly positively correlated with SPEI in June and July, and lowest temperature in October of current year. The iWUE of trees at Ansai was significantly positively correlated with relative humidity and precipitation in June of the current year, but negatively correlated with minimum temperature in May, relative humidity in June, and temperature and maximum temperature in July of current year. A significant positive correlation between iWUE of trees at Jixian and lowest temperature in June of current year was detected. At the annual scale, the BAI of trees at Ansai was positively correlated with precipitation and SPEI, but no significant relationship was observed for trees at Jixian. However, the iWUE of trees at both sites was significantly affected by precipitation. Path analysis showed that SPEI and minimum temperature had a direct effect on BAI and iWUE of trees at Ansai, whereas precipitation and average temperature indirectly affected BAI and iWUE through SPEI. The highest temperature had a direct effect on tree growth at Jixian, whereas precipitation, minimum temperature, and average temperature had direct effects on iWUE. These results suggested that SPEI was the main climatic factor that affected the growth of R. pseudoacacia, while Ci was an important physiological factor. Our results could provide reference for the protection and management of R. pseudoacacia plantations under climate change.

Light-Emitting Diodes Modify Medicinal Quality of Mown Rabdosia rubescens, with Changes in Growth, Physiology, and Antioxidant Activity, under Drought Stress.

Medicinal plants accommodated by understory habitats can easily suffer over-exploitation in the heavy harvest of natural products. It is necessary to develop a sustainable cultural protocol to provide high-quality stocks for efficient regeneration. Drought places stress on medicinal plants during their culture by limiting new sprout growth and reducing the quality of medicinal extracts. Artificial mediating approaches should be considered in a sustainable regime of medicinal plant culture to test the potential tradeoff between resistance to drought and production ability. In this study, Rabdosia rubescens seedlings were raised in three light-emitting diode (LED) spectra from red (71.7% red, 14.6% green, 13.7% blue), green (26.2% red, 17.4% green, 56.4% blue), and blue (17.8% red, 33.7% green, 48.5% blue) lights. Mown seedlings were subjected to a simulated drought event. Drought stressed the seedlings by reducing the growth, dry mass, nitrogen (N) uptake, and oridonin content. Mowing increased the oridonin content but decreased total C and N accumulation and the δ13C level. The red light benefitted starch accumulation only under the well-watered condition, and the green light induced an upregulation of δ13C but decreased antioxidant activity. Oridonin content was negatively associated with combined δ13C and catalase activity. Overall, either mowing or blue light can be recommended for the culture of R. rubescens to increase oridonin content, alleviating some of the negative consequences of drought.

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.

Triple-transgenic soybean in conjunction with glyphosate drive patterns in the rhizosphere microbial community assembly.

Plant roots continuously influence the rhizosphere, which also serves as a recruitment site for microorganisms with desirable functions. The development of genetically engineered (GE) crop varieties has offered unparalleled yield advantages. However, in-depth research on the effects of GE crops on the rhizosphere microbiome is currently insufficient. We used a triple-transgenic soybean cultivar (JD606) that is resistant to insects, glyphosate, and drought, along with its control, ZP661, and JD606 treated with glyphosate (JD606G). Using 16S and ITS rDNA sequencing, their effects on the taxonomy and function of the bacterial and fungal communities in the rhizosphere, surrounding, and bulk soil compartment niches were determined. Alpha diversity demonstrated a strong influence of JD606 and JD606G on bacterial Shannon diversity. Both treatments significantly altered the soil's pH and nitrogen content. Beta diversity identified the soil compartment niche as a key factor with a significant probability of influencing the bacterial and fungal communities associated with soybeans. Further analysis showed that the rhizosphere effect had a considerable impact on bacterial communities in JD606 and JD606G soils but not on fungal communities. Microbacterium, Bradyrhizobium, and Chryseobacterium were found as key rhizobacterial nodes. In addition, the LEfSe analysis identified biomarker taxa with plant-beneficial attributes, demonstrating rhizosphere-driven microbial recruitment. FUNGuild, Bugbase, and FAPROTAX functional predictions showed that ZP661 soils had more plant pathogen-associated microbes, while JD606 and JD606G soils had more stress-tolerance, nitrogen, and carbon cycle-related microbes. Bacterial rhizosphere networks had more intricate topologies than fungal networks. Furthermore, correlation analysis revealed that the bacteria and fungi with higher abundances exhibited varying degrees of positive and negative correlations. Our findings shed new light on the niche partitioning of bacterial and fungal communities in soil. It also indicates that following triple-transgenic soybean cultivation and glyphosate application, plant roots recruit microbes with beneficial taxonomic and functional traits in the rhizosphere.

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.

Wogonin inhibits latent HIV-1 reactivation by downregulating histone crotonylation.

BACKGROUND: Wogonin, a flavone isolated from Scutellaria baicalensis Georgi, is a commonly used phytochemical with anti-inflammatory and antitumor properties. However, the antiviral activity of wogonin against human immunodeficiency virus type 1 (HIV-1) has not been reported. PURPOSE: The current study aimed to explore whether wogonin can suppress latent HIV-1 reactivation and the mechanism of wogonin in inhibiting proviral HIV-1 transcription. METHODS: We assessed the effects of wogonin on HIV-1 reactivation using flow cytometry, cytotoxicity assay, quantitative PCR (qPCR), viral quality assurance (VQA), and western blot analysis. RESULTS: Wogonin, a flavone isolated from S. baicalensis, significantly inhibited the reactivation of latent HIV-1 in cellular models and in primary CD4+ T cells from antiretroviral therapy (ART)-suppressed individuals ex vivo. Wogonin exhibited low cytotoxicity and long-lasting inhibition of HIV-1 transcription. Triptolide is a latency-promoting agent (LPA) that inhibits HIV-1 transcription and replication; wogonin had a stronger ability to inhibit HIV-1 latent reactivation than triptolide. Mechanistically, wogonin inhibited the reactivation of latent HIV-1 by inhibiting the expression of p300, a histone acetyltransferase, and decreasing the crotonylation of histone H3/H4 in the HIV-1 promoter region. CONCLUSION: Our study found that wogonin is a novel LPA that can inhibit HIV-1 transcription by HIV-1 epigenetic silencing, which could bear promising significance for future applications of HIV-1 functional cure.

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.

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.

Discrepancies in rhizobacterial assembly caused by glyphosate application and herbicide-tolerant soybean Co-expressing GAT and EPSPS.

There are concerns that the innovation of genetically modified herbicide-tolerant (GMHT) plants, as well as the application of herbicide to such GMHT plants, could have an impact on ecological interactions and unintentionally harm non-targeted organisms. Consequently, we intend to use full-length 16 S rDNA amplicon sequencing to examine changes in the bacterial community in the rhizosphere of GMHT soybean (Z106) harboring 5-enolpyruvylshikimate-3-phosphate synthase and Glyphosate N-acetyltransferase genes and GMHT soybean treated with glyphosate (Z106G). Glyphosate application significantly impacted bacterial alpha diversity (species richness, and Shannon diversity). Permutational multivariate analysis of variance of beta diversity demonstrated that soil compartments and growth stages had a substantial impact on soybean rhizobacterial communities (soil compartments, growth stages, P = 0.001). Community composition revealed that Z106G soils were abundant in Taibaiella and Arthrobacter pascens at maturity, while Chryseobacterium joostei and Stenotrophomonas maltophilia predominated in Z106 soils during flowering. Nitrogen-fixing and phosphate-solubilizing microbes were found in higher proportions in the rhizosphere than in bulk soil, with Sinorhizobium being more abundant in Z106 and Bacillus and Stenotrophomonas being more prevalent in Z106G rhizosphere soils. Collectively, our findings suggest glyphosate application and glyphosate-tolerant soybean as potential regulators of soybean rhizobacterial composition.

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.