Spatial profiling of chromatin accessibility in mouse and human tissues.

Cellular function in tissue is dependent on the local environment, requiring new methods for spatial mapping of biomolecules and cells in the tissue context1. The emergence of spatial transcriptomics has enabled genome-scale gene expression mapping2-5, but the ability to capture spatial epigenetic information of tissue at the cellular level and genome scale is lacking. Here we describe a method for spatially resolved chromatin accessibility profiling of tissue sections using next-generation sequencing (spatial-ATAC-seq) by combining in situ Tn5 transposition chemistry6 and microfluidic deterministic barcoding5. Profiling mouse embryos using spatial-ATAC-seq delineated tissue-region-specific epigenetic landscapes and identified gene regulators involved in the development of the central nervous system. Mapping the accessible genome in the mouse and human brain revealed the intricate arealization of brain regions. Applying spatial-ATAC-seq to tonsil tissue resolved the spatially distinct organization of immune cell types and states in lymphoid follicles and extrafollicular zones. This technology progresses spatial biology by enabling spatially resolved chromatin accessibility profiling to improve our understanding of cell identity, cell state and cell fate decision in relation to epigenetic underpinnings in development and disease.

EPSTI1 promotes osteoclast differentiation and bone resorption by PKR/NF-κB signaling.

BACKGROUND: Epithelial stromal interaction 1 (EPSTI1) plays an important role in M1 macrophages, which induce osteoclastogenesis. One recent genome-wide association study (GWAS) involving 426,824 individuals has shown that EPSTI1 is strongly associated with osteoporosis (P < 5E-8). Therefore, we speculate that EPSTI1 participates in the modulation of osteoporosis through osteoclastogenesis. The roles of EPSTI1 in osteoclastogenesis and bone resorption remain unclear. METHODS: Femur specimens were collected from osteoporotic patients and control patients. Immunofluorescence staining was used to detect the expression of EPSTI1 and signaling pathways. The osteoclastic potential of RAW264.7 cells with Sh-EPSTI1 lentivirus infection was tested using tartrate-resistant acid phosphatase (TRAP) staining, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting was also used to examine signaling pathways. RESULTS: In this study, EPSTI1 was found to be significantly increased in tartrate-resistant acid phosphatase positive (ACP5+) osteoclasts of bone sections from osteoporotic patients. Next, we identified EPSTI1 as a positive regulator of osteoclastogenesis and osteoclast differentiation capability. Diminished EPSTI1 expression resulted in reduced osteoclastic resorption. Mechanistically, EPSTI1-driven osteoclastogenesis was regulated by NF-κB pathway, which was mediated by the phosphorylation of protein kinase R (p-PKR). Furthermore, EPSTI1 participating in the modulation of osteoporosis via PKR/NF-κB pathway was also verified in the bone samples of osteoporotic patients. CONCLUSIONS: Collectively, our findings suggest that EPSTI1 may regulate osteoclast differentiation and bone resorption through PKR/NF-κB pathway and in vivo experiments are needed to further verify EPSTI1 as the therapy target for osteoporosis.

Reproducible and High-Performance WOLEDs Based on Independent High-Efficiency Triplet Harvesting of Yellow Hot-Exciton ESIPT and Blue TADF Emitters.

Hot exciton organic light-emitting diode (OLED) emitters can balance the high performance of a device and reduce efficiency roll-off by fast reverse intersystem crossing from high-lying triplets (hRISC). In this study, an excited-state intramolecular proton transfer (ESIPT) fluorophore of 2-(benzo[d]thiazol-2-yl)-4-(pyren-1-yl)phenol (PyHBT) with the typical characteristic properties of a hot exciton is developed. With high efficiency of utilization of the exciton (91%), its yellow OLED exhibited high external quantum efficiency (EQE) of 5.6%, current efficiency (CE) of 16.8 cd A-1 , and power efficiency (PE) of 17.3 lm W-1 . The performance of the yellow emissive "hot exciton" ESIPT fluorophores is among the highest recorded. Due to the large Stokes shift of the ESIPT emitter, non-energy-transferred high-performance white OLEDs (WOLEDs) are developed, which are reproducible and highly efficient. This is possible because of the independent harvesting of most of the triplets in both complementary-color emitters without the interference of energy transfer. The PyHBT-based WOLEDs exhibit a maximum EQE of 14.3% and CE of 41.1 cd A-1 , which facilitates the high-yield mass production of inexpensive WOLEDs.

Global nitrous oxide emissions from livestock manure during 1890-2020: An IPCC tier 2 inventory.

Nitrous oxide (N2O) emissions from livestock manure contribute significantly to the growth of atmospheric N2O, a powerful greenhouse gas and dominant ozone-depleting substance. Here, we estimate global N2O emissions from livestock manure during 1890-2020 using the tier 2 approach of the 2019 Refinement to the 2006 IPCC Guidelines. Global N2O emissions from livestock manure increased by ~350% from 451 [368-556] Gg N year-1 in 1890 to 2042 [1677-2514] Gg N year-1 in 2020. These emissions contributed ~30% to the global anthropogenic N2O emissions in the decade 2010-2019. Cattle contributed the most (60%) to the increase, followed by poultry (19%), pigs (15%), and sheep and goats (6%). Regionally, South Asia, Africa, and Latin America dominated the growth in global emissions since the 1990s. Nationally, the largest emissions were found in India (329 Gg N year-1), followed by China (267 Gg N year-1), the United States (163 Gg N year-1), Brazil (129 Gg N year-1) and Pakistan (102 Gg N year-1) in the 2010s. We found a substantial impact of livestock productivity, specifically animal body weight and milk yield, on the emission trends. Furthermore, a large spread existed among different methodologies in estimates of global N2O emission from livestock manure, with our results 20%-25% lower than those based on the 2006 IPCC Guidelines. This study highlights the need for robust time-variant model parameterization and continuous improvement of emissions factors to enhance the precision of emission inventories. Additionally, urgent mitigation is required, as all available inventories indicate a rapid increase in global N2O emissions from livestock manure in recent decades.

miR-541 is associated with the prognosis of liver cirrhosis and directly targets JAG2 to inhibit the activation of hepatic stellate cells.

BACKGROUND: The activation of hepatic stellate cells (HSCs) has been emphasized as a leading event of the pathogenesis of liver cirrhosis, while the exact mechanism of its activation is largely unknown. Furthermore, the novel non-invasive predictors of prognosis in cirrhotic patients warrant more exploration. miR-541 has been identified as a tumor suppressor in hepatocellular carcinoma and a regulator of fibrotic disease, such as lung fibrosis and renal fibrosis. However, its role in liver cirrhosis has not been reported. METHODS: Real-time PCR was used to detect miR-541 expression in the liver tissues and sera of liver cirrhosis patients and in the human LX-2. Gain- and loss-of-function assays were performed to evaluate the effects of miR-541 on the activation of LX-2. Bioinformatics analysis and a luciferase reporter assay were conducted to investigate the target gene of miR-541. RESULTS: miR-541 was downregulated in the tissues and sera of patients with liver cirrhosis, which was exacerbated by deteriorating disease severity. Importantly, the lower expression of miR-541 was associated with more episodes of complications including ascites and hepatic encephalopathy, a shorter overall lifespan, and decompensation-free survival. Moreover, multivariate Cox's regression analysis verified lower serum miR-541 as an independent risk factor for liver-related death in cirrhotic patients (HR = 0.394; 95% CI: 0.164-0.947; P = 0.037). miR-541 was also decreased in LX-2 cells activated by TGF-ß and the overexpression of miR-541 inhibited the proliferation, activation and hydroxyproline secretion of LX-2 cells. JAG2 is an important ligand of Notch signaling and was identified as a direct target gene of miR-541. The expression of JAG2 was upregulated in the liver tissues of cirrhotic patients and was inversely correlated with miR-541 levels. A rescue assay further confirmed that JAG2 was involved in the function of miR-541 when regulating LX-2 activation and Notch signaling. CONCLUSIONS: Dysregulation of miR-541/JAG2 axis might be a as a new mechanism of liver fibrosis, and miR-541 could serve as a novel non-invasive biomarker and therapeutic targets for liver cirrhosis.

The Roles of the Two-Component System, MtrAB, in Response to Diverse Cell Envelope Stresses in Dietzia sp. DQ12-45-1b.

Two-component systems (TCSs) act as common regulatory systems allowing bacteria to detect and respond to multiple environmental stimuli, including cell envelope stress. The MtrAB TCS of Actinobacteria is critical for cell wall homeostasis, cell proliferation, osmoprotection, and antibiotic resistance, and thus is found to be highly conserved across this phylum. However, how precisely the MtrAB TCS regulates cellular homeostasis in response to environmental stress remains unclear. Here, we show that the MtrAB TCS plays an important role in the tolerance to different types of cell envelope stresses, including environmental stresses (i.e., oxidative stress, lysozyme, SDS, osmotic pressure, and alkaline pH stresses) and envelope-targeting antibiotics (i.e., isoniazid, ethambutol, glycopeptide, and ß-lactam antibiotics) in Dietzia sp. DQ12-45-1b. An mtrAB mutant strain exhibited slower growth compared to the wild-type strain and was characterized by abnormal cell shapes when exposed to various environmental stresses. Moreover, deletion of mtrAB resulted in decreased resistance to isoniazid, ethambutol, and ß-lactam antibiotics. Further, Cleavage under targets and tagmentation sequencing (CUT&Tag-seq) and electrophoretic mobility shift assays (EMSAs) revealed that MtrA binds the promoters of genes involved in peptidoglycan biosynthesis (ldtB, ldtA, murJ), hydrolysis (GJR88_03483, GJR88_4713), and cell division (ftsE). Together, our findings demonstrated that the MtrAB TCS is essential for the survival of Dietzia sp. DQ12-45-1b under various cell envelope stresses, primarily by controlling multiple downstream cellular pathways. Our work suggests that TCSs act as global sensors and regulators in maintaining cellular homeostasis, such as during episodes of various environmental stresses. The present study should shed light on the understanding of mechanisms for bacterial adaptivity to extreme environments. IMPORTANCE The multilayered cell envelope is the first line of bacterial defense against various extreme environments. Bacteria utilize a large number of sensing and regulatory systems to maintain cell envelope homeostasis under multiple stress conditions. The two-component system (TCS) is the main sensing and responding apparatus for environmental adaptation. The MtrAB TCS highly conserved in Actinobacteria is critical for cell wall homeostasis, cell proliferation, osmoprotection, and antibiotic resistance. However, how MtrAB works with regard to signals impacting changes to the cell envelope is not fully understood. Here, we found that in the Actinobacterium Dietzia sp. DQ12-45-1b, a TCS named MtrAB is pivotal for ensuring normal cell growth as well as maintaining proper cell morphology in response to various cell envelope stresses, namely, by regulating the expression of cell envelope-related genes. Our findings should greatly advance our understanding of the adaptive mechanisms responsible for maintaining cell integrity in times of sustained environmental shocks.

A 130-year global inventory of methane emissions from livestock: Trends, patterns, and drivers.

Livestock contributes approximately one-third of global anthropogenic methane (CH4 ) emissions. Quantifying the spatial and temporal variations of these emissions is crucial for climate change mitigation. Although country-level information is reported regularly through national inventories and global databases, spatially explicit quantification of century-long dynamics of CH4 emissions from livestock has been poorly investigated. Using the Tier 2 method adopted from the 2019 Refinement to 2006 IPCC guidelines, we estimated CH4 emissions from global livestock at a spatial resolution of 0.083° (~9 km at the equator) during the period 1890-2019. We find that global CH4 emissions from livestock increased from 31.8 [26.5-37.1] (mean [minimum-maximum of 95% confidence interval) Tg CH4 yr-1 in 1890 to 131.7 [109.6-153.7] Tg CH4 yr-1 in 2019, a fourfold increase in the past 130 years. The growth in global CH4 emissions mostly occurred after 1950 and was mainly attributed to the cattle sector. Our estimate shows faster growth in livestock CH4 emissions as compared to the previous Tier 1 estimates and is ~20% higher than the estimate from FAOSTAT for the year 2019. Regionally, South Asia, Brazil, North Africa, China, the United States, Western Europe, and Equatorial Africa shared the majority of the global emissions in the 2010s. South Asia, tropical Africa, and Brazil have dominated the growth in global CH4 emissions from livestock in the recent three decades. Changes in livestock CH4 emissions were primarily associated with changes in population and national income and were also affected by the policy, diet shifts, livestock productivity improvement, and international trade. The new geospatial information on the magnitude and trends of livestock CH4 emissions identifies emission hotspots and spatial-temporal patterns, which will help to guide meaningful CH4 mitigation practices in the livestock sector at both local and global scales.

Design, synthesis and biological evaluation of nitrofuran-1,3,4-oxadiazole hybrids as new antitubercular agents.

Three series of novel nitrofuran-1,3,4-oxadiazole hybrids were designed and synthesized as new anti-TB agents. The structure activity relationship study indicated that the linkers and the substituents on the oxadiazole moiety greatly influence the activity, and the substituted benzenes are more favoured than the cycloalkyl or heterocyclic groups. Besides, the optimal compound in series 2 was active against both MTB H37Rv strain and MDR-MTB 16883 clinical isolate and also displayed low cytotoxicity, low inhibition of hERG and good oral PK, indicating its promising potential to be a lead for further structural modifications.

Functional characterization and catalytic activity improvement of BAHD acyltransferase from Celastrus angulatus Maxim.

MAIN CONCLUSION: A BAHD terpene alcohol acyltransferase, CaAT20, was identified from Celastrus angulatus Maxim, expressed in E. coli and functionally characterized. S405A mutant of CaAT20 increased the enzyme activity. Acylation is a diversely physiological process in the biosynthesis of plant secondary metabolites. Plant BAHD acyltransferases play an important role in the modification of volatile esters with biological activities. In this research, a BAHD acyltransferase (CaAT20) was identified from Celastrus angulatus Maxim and the function of this enzyme was characterized. CaAT20 could convert geraniol to geranyl esters by using benzoyl-CoA and acetyl-CoA as the acyl donors respectively. Furthermore, the catalytic activity of CaAT20 for benzoyl-CoA was higher than that of acetyl-CoA. Site-directed mutation of CaAT20 was carried out based on the results of molecular simulation. In vitro site-directed mutant S405A of CaAT20 increased the volume of binding cavity so as to facilitate the entry of geraniol, indicating a more efficient acylation for geraniol and benzoyl-CoA. Our research provides new insight for the catalytic functions of CaAT20.

Comparative DNA methylome analysis of estrus ewes reveals the complex regulatory pathways of sheep fecundity.

BACKGROUND/AIMS: Sheep are important livestock with variant ovulation rate and fertility. Dorset sheep is a typical breed with low prolificacy, whereas Small Tail Han sheep with FecB mutation (HanBB) have hyperprolificacy. Our previous studies have revealed the gene expression difference between the ovaries from Dorset and HanBB sheep contributes to the difference of fecundity, however, what leads to these gene expression difference remains unclear. DNA methylation, an important epigenetic process, plays a crucial role in gene expression regulation. METHODS: In the present study, we constructed a methylated DNA immunoprecipitation combined with high throughput sequencing (MeDIP-seq) strategy to investigate the differentially methylated genes between the Dorset and HanBB ovaries. RESULTS: Our findings suggest the genes involved in immune response, branched-chain amino acid metabolism, cell growth and cell junction were differentially methylated in or around the gene body regions. CONCLUSIONS: These findings provide prospective insights on the epigenetic basis of sheep fecundity.

Characteristics of 3586 Han and Uyghur patients with peptic ulcer in Xinjiang. / 新疆3586ä¾‹æ±‰æ—å’Œç»´å¾å°”æ—æ¶ˆåŒ–æ€§æºƒç–¡ç–¾ç— ç‰¹å¾.

OBJECTIVES: To compare the features of patients with peptic ulcer between Han and Uyghur ethnicity from 2013 to 2018 in Xinjiang and to provide the evidence of prevention and treatment for the different ethnicity. METHODS: Data of 3 586 patients with peptic ulcer (3 293 Han and 293 Uyghur) in the Karamay Central Hospital of Xinjiang, including the detection rate of peptic ulcer, helicobacter pylori (Hp) detection rate of population, season, gender, lesion location and complication, were collected from January 2013 to December 2018 and compared between 2 nationalities. RESULTS: There were significant difference in the detection rate of peptic ulcer and population's Hp between Han and Uyghur (P<0.01). The detection rates for peptic ulcer of Han were sustainable declined from 15.20% to 10.23%, while Uyghur's detective rates for peptic ulcer were raised again from 17.49% to 8.38%. The Hp detection rate of Uyghur's population was higher than that of Han (P<0.01). There were significant difference in the season's detection rate for peptic ulcer between Han and Uyghur (P<0.01). The detection rate for peptic ulcer of Han was the highest in the winter, while that of Uyghur was the highest in the spring. The detective rate of Uyghur's peptic ulcer was significant higher than that of Han in the spring (P<0.01). The detection rates for peptic ulcer of 2 nationality were the highest at ≤25 age groups, the detection rate for Uyghur's peptic ulcer was higher than that of Han at ≤35 age groups (P<0.05). There were more men than women in peptic ulcer in the 2 nationalities. The approximate proportion was 2꞉1. The rates of multiple gastric ulcer and compound duodenal ulcer of Han were more than those of Uyghur (P<0.05), but the rate for pyloric obstruction of Uyghur patient was higher than that of Han (P<0.05). CONCLUSIONS: There are statistical difference in detection rate of PU, Hp detection rate of population, morbidity season, age, complication and the rate of complex ulcer between Han and Uyghur, However, there aren't statistical difference in Hp detection rate of peptic ulcer patient, the gender, lesion location between the 2 nationalities during last 6 years.

De novo leaf and root transcriptome analysis to explore biosynthetic pathway of Celangulin V in Celastrus angulatus maxim.

BACKGROUND: Celastrus angulatus Maxim is a kind of crucial and traditional insecticidal plant widely distributed in the mountains of southwest China. Celangulin V is the efficient insecticidal sesquiterpenoid of C. angulatus and widely used in pest control in China, but the low yield and discontinuous supply impeded its further popularization and application. Fortunately, the development of synthetic biology provided an opportunity for sustainable supply of Celangulin V, for which understanding its biosynthetic pathway is indispensable. RESULTS: In this study, six cDNA libraries were prepared from leaf and root of C. angulatus before global transcriptome analyses using the BGISEQ-500 platform. A total of 104,950 unigenes were finally obtained with an average length of 1200 bp in six transcriptome databases of C. angulatus, in which 51,817 unigenes classified into 25 KOG classifications, 39,866 unigenes categorized into 55 GO functional groups, and 48,810 unigenes assigned to 135 KEGG pathways, 145 of which were putative biosynthetic genes of sesquiterpenoid and triterpenoid. 16 unigenes were speculated to be related to Celangulin V biosynthesis. De novo assembled sequences were verified by Quantitative Real-Time PCR (qRT-PCR) analysis. CONCLUSIONS: This study is the first report on transcriptome analysis of C. angulatus, and 16 unigenes probably involved in the biosynthesis of Celangulin V were finally collected. The transcriptome data will make great contributions to research for this specific insecticidal plant and the further gene mining for biosynthesis of Celangulin V and other sesquiterpene polyol esters.

Role of the Group 2 Mrp sodium/proton antiporter in rapid response to high alkaline shock in the alkaline- and salt-tolerant Dietzia sp. DQ12-45-1b.

The six- and seven-subunit Na+/H+ antiporters (Mrp) are widely distributed in bacteria. They are reported to be integral for pH homeostasis in alkaliphilic bacteria when adapting to high pH environments. In this study, operons encoding for the six-subunit Na+/H+ antiporters were found in the genomes of all studied Dietzia strains, which have different alkaline-resistant abilities. Disruption of the operon in the strain Dietzia sp. DQ12-45-1b which leads to declined growth in presence of hypersaline and alkaline conditions suggested that the six-subunit Na+/H+ antiporter played an important role in hypersaline and alkaline resistance. Although the complexes DqMrp from DQ12-45-1b (strain with high alkaline resistance) and DaMrp from D. alimentaria 72T (strain with low alkaline resistance) displayed Na+(Li+)/H+ antiport activities, they functioned optimally at different pH levels (9.0 for DQ12-45-1b and 8.0 for 72T). While both antiporters functioned properly to protect Escherichia coli cells from salt shock, only the DqMrp-containing strain survived the high alkaline shock. Furthermore, real-time PCR results showed that the expression of mrpA and mrpD induced only immediately after DQ12-45-1b cells were subjected to the alkaline shock. These results suggested that the expression of DqMrp might be induced by a pH gradient across the cell membrane, and DqMrp mainly functioned at an early stage to respond to the alkaline shock.

Genome-wide mRNA-seq profiling reveals predominant down-regulation of lipid metabolic processes in adipose tissues of Small Tail Han than Dorset sheep.

Small Tail Han and Dorset sheep are two different sheep with distinguished morphologies in fat depositions. In order to characterize their gene expression profiles, our present study took the advantages of RNA sequencing technology with the aims to identify important genes regulating the metabolisms in adipose tissues of two different sheep. In obtained high quality sequencing reads, 85.9 (Han) and 86.1% (Dorset) were uniquely aligned to Oar v3.1 sheep reference genome, and over 76% of bases in mapped reads corresponded to mRNA. Using R package EBSeq, we identified 602 differentially expressed genes. Using the 602 genes, GO analysis showed that 30 out of 56 significantly enriched biological processes were metabolism related, of which the most significant one was triglyceride biosynthetic process. The KEGG pathway analysis indicated the down-regulation of several fat metabolic pathways. The predominant down-regulation of massive metabolic processes, particularly the lipid metabolism, in adipose tissues of Han sheep could explain, at least in part, the distinguished fat deposition between two different sheep, and our data constitute a basic picture of transcriptomes in these sheep for better understanding of underline biological mechanism in their lipid metabolisms.

Synthesis of quinolinones with palladium-catalyzed oxidative annulation between acrylamides and arynes.

An unprecedented palladium-catalyzed oxidative annulation of acrylamides with benzyne precursors has been successfully developed. By using this mild "N-H activation/Heck reaction" method, a wide variety of quinolinones were conveniently prepared in one step with high efficiency.

SERS investigation of ciprofloxacin drug molecules on TiO2 nanoparticles.

In this paper, TiO2 nanoparticles (NPs) with different crystallinity served as SERS-active substrates for SERS detection of ciprofloxacin (CIP) drug molecules for the first time. CIP is close to the surface of the TiO2 substrate through the carboxyl group. The mutual SERS enhancement behaviors between CIP molecules and TiO2 NPs were discovered, which are attributed to the contribution of the TiO2-to-molecule charge-transfer mechanism. The crystallinity of TiO2 NPs, the pH value of adsorption solution and the adsorption time have significant influences on the interaction and the SERS behavior between CIP and TiO2. When the calcination temperature of TiO2 NPs is 450 °C, the pH value of adsorption solution is 6 and the adsorption time is 9 h, the CIP molecules on TiO2 NPs exhibit the largest SERS enhancement.

Chirality-driven strong thioredoxin reductase inhibition.

Overexpression of thioredoxin reductase (TXNRD) plays crucial role in tumorigenesis. Therefore, designing TXNRD inhibitors is a promising strategy for targeted anticancer drug development. However, poor selectivity has always been a challenge, resulting in unavoidable toxicity in clinic. Herein we demonstrate a strategy to develop highly selective chiral metal complexes-based TXNRD inhibitors. By manipulating the conformation of two distinct weakly interacting groups, we optimize the compatibility between the drug and the electrophilic group within the active site of TXNRD to enhance their non-covalent interaction, thus effectively avoids the poor selectivity deriving from covalent drug interaction, on the basis of ensuring the strong inhibition. Detailed experimental and computational results demonstrate that the chiral isomeric drugs bind to the active site of TXNRD, and the interaction strength is well modulated by chirality. Especially, the meso-configuration, in which the two large sterically hindered active groups are positioned on opposite sides of the drug, exhibits the highest number of non-covalent interactions and most effective inhibition on TXNRD. Taken together, this work not only provides a novel approach for developing highly selective proteinase inhibitors, but also sheds light on possible underlying mechanisms for future application.

Visual and refractive outcomes of opposite clear corneal incision combined with rotationally asymmetric multifocal intraocular lens implantation.

Purpose: To evaluate the visual and refractive outcomes of astigmatic cataract patients following opposite clear corneal incision (OCCI) combined with rotationally asymmetric multifocal intraocular lens (IOL) implantation. Setting: Department of Ophthalmology, Zhongshan Hospital (Xiamen), Fudan University, People's Republic of China. Design: Retrospective cohort study. Methods: This study comprised 58 cataract eyes of 54 patients with corneal astigmatism who underwent phacoemulsification and rotationally asymmetric multifocal IOL implantation which received either OCCI (OCCI group) or a single clear corneal incision (SCCI group). The follow-up period was 3 months after surgery. Distance, intermediate and near visual acuity, refractive outcomes, and corneal anterior keratometry were compared between the two groups. Vector analysis was used to evaluate astigmatism correction. Results: Three months after surgery, the distance, intermediate and near visual acuity, and sphere remained comparable between the two groups, but a significant difference was detected in residual astigmatism and anterior corneal keratometric astigmatism. In the OCCI group, the residual astigmatism and keratometric astigmatism were -0.60 ± 0.29 D and 0.59 ± 0.28 D, respectively, which were lower than those in SCCI groups (-1.18 ± 0.47 D and 1.15 ± 0.45 D, both p < 0.05). In vector analysis, the difference vector (DV), angle of error (AoE), absolute AoE, index of success (IoS) and correction index (CI) were statistically significantly different between the two groups (p < 0.05). Conclusion: OCCI combined with rotationally asymmetric multifocal intraocular lens implantation showed predictable and desirable efficacy in treating cataract patients with astigmatism.

Efficacy of borneol-gypsum in skin regeneration and pain control in toxic epidermal necrolysis: A case report.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a life-threatening dermatological emergency mainly induced by drug hypersensitivity reactions. Standard management includes discontinuation of culprit drug and application of immunomodulatory therapy. However, mortality remains high due to complications like septic shock and multiorgan failures. Innovative approaches for skin care are crucial. This report introduces borneol-gypsum, a traditional Chinese drug but a novel dressing serving as an adjuvant of TEN therapy, might significantly improve skin conditions and patient outcomes in TEN. CASE SUMMARY: A 38-year-old woman diagnosed with eosinophilic granulomatosis with polyangiitis experienced gangrenous complications and motor nerve involvement. After initial treatment of high-dose corticosteroids and cyclophosphamide, symptom of foot drop improved, absolute eosinophil counts decreased, while limb pain sustained. Duloxetine was added to alleviate her symptom. Subsequently, TEN developed. Additional topical application of borneol-gypsum dressing not only protected the skin lesions from infection but also significantly eased localized pain. This approach demonstrated its merit in TEN management by promoting skin healing and potentially reducing infection risks. CONCLUSION: Borneol-gypsum dressing is a promising adjuvant that could significantly improve TEN management, skin regeneration, and patient comfort.

Identification of dihydroquinolizinone derivatives with nitrogen heterocycle moieties as new anti-HBV agents.

The sustained loss of HBsAg is considered a pivotal indicator for achieving functional cure of HBV. Dihydroquinolizinone derivatives (DHQs) have demonstrated remarkable inhibitory activity against HBsAg both in vitro and in vivo. However, the reported neurotoxicity associated with RG7834 has raised concerns regarding the development of DHQs. In this study, we designed and synthesized a series of DHQs incorporating nitrogen heterocycle moieties. Almost all of these compounds exhibited potent inhibition activity against HBsAg, with IC50 values at the nanomolar level. Impressively, the compound (S)-2a (10 µM) demonstrated a comparatively reduced impact on the neurite outgrowth of HT22 cells and isolated mouse DRG neurons in comparison to RG7834, thereby indicating a decrease in neurotoxicity. Furthermore, (S)-2a exhibited higher drug exposures than RG7834. The potent anti-HBV activity, reduced neurotoxicity, and favorable pharmacokinetic profiles underscore its promising potential as a lead compound for future anti-HBV drug discovery.