Virologic outcomes with tenofovir-lamivudine-dolutegravir in adults failing PI-based second-line ART.

Background: In South African antiretroviral guidelines, selected patients failing second-line protease inhibitor (PI)-based therapy qualify for genotypic resistance testing - those with PI resistance receive darunavir-based third-line regimens; those without PI resistance continue current regimen with adherence support. The Western Cape province, from September 2020, implemented a strategy of tenofovir-lamivudine-dolutegravir (TLD) for patients, provided there was no tenofovir resistance, irrespective of PI resistance. Objectives: To evaluate virologic outcomes with TLD among adults failing second-line PI regimens with no tenofovir resistance. Method: An observational cohort study comparing outcomes in patients switched to TLD with those continuing the same PI or switched to darunavir-based regimens. Follow-up was until virologic suppression (HIV-1 RNA < 400 copies/mL), or at the point of censoring. Results: One hundred and thirty-three patients switched to TLD, 101 to darunavir-based regimens, and 121 continued with the same PI. By 12 months, among patients with PI resistance, 42/47 (89%) in the TLD group had HIV-1 RNA < 400 copies/mL compared to 91/99 (92%) in the darunavir group (hazard ratio, 1.11; 95% confidence interval, 0.77-1.60). In patients without PI resistance, 66/86 (77%) in the TLD group had HIV-1 RNA < 400 copies/mL compared to 42/120 (35%) in those continuing with the same PI (hazard ratio, 4.03; 95% confidence interval, 2.71-5.98). Two patients receiving TLD developed virologic failure with high-level dolutegravir resistance. Conclusion: Amongst patients failing second-line PI with no PI resistance, switching to TLD was associated with higher virologic suppression, likely due to improved adherence. Virologic outcomes were similar in patients with PI resistance switched to darunavir-based regimens or TLD.

The SmMYC2-SmMYB36 complex is involved in methyl jasmonate-mediated tanshinones biosynthesis in Salvia miltiorrhiza.

The jasmonic acid (JA) signaling pathway plays an important role in promoting the biosynthesis of tanshinones. While individual transcription factors have been extensively studied in the context of tanshinones biosynthesis regulation, the influence of methyl jasmonate (MeJA)-induced transcriptional complexes remains unexplored. This study elucidates the positive regulatory role of the basic helix-loop-helix protein SmMYC2 in tanshinones biosynthesis in Salvia miltiorrhiza. SmMYC2 not only binds to SmGGPPS1 promoters, activating their transcription, but also interacts with SmMYB36. This interaction enhances the transcriptional activity of SmMYC2 on SmGGPPS1, thereby promoting tanshinones biosynthesis. Furthermore, we identified three JA signaling repressors, SmJAZ3, SmJAZ4, and SmJAZ8, which interact with SmMYC2. These repressors hindered the transcriptional activity of SmMYC2 on SmGGPPS1 and disrupted the interaction between SmMYC2 and SmMYB36. MeJA treatment triggered the degradation of SmJAZ3 and SmJAZ4, allowing the SmMYC2-SmMYB36 complex to subsequently activate the expression of SmGGPPS1, whereas SmJAZ8 inhibited MeJA-mediated degradation due to the absence of the LPIARR motif. These results demonstrate that the SmJAZ-SmMYC2-SmMYB36 module dynamically regulates the JA-mediated accumulation of tanshinones. Our results reveal a new regulatory network for the biosynthesis of tanshinones. This study provides valuable insight for future research on MeJA-mediated modulation of tanshinones biosynthesis.

Effect of Cytochrome P450 3A4 on Tissue Distribution of Humantenmine, Koumine, and Gelsemine, three Alkaloids from the Toxic Plant Gelsemium.

Humantenmine, koumine, and gelsemine are three indole alkaloids found in the highly toxic plant Gelsemium. Humantenmine was the most toxic, followed by gelsemine and koumine. The aim of this study was to investigate and analyze the effects of these three substances on tissue distribution and toxicity in mice pretreated with the Cytochrome P450 3A4 (CYP3A4) inducer ketoconazole and the inhibitor rifampicin. The in vivo test results showed that the three alkaloids were absorbed rapidly and had the ability to penetrate the blood-brain barrier. At 5minutes after intraperitoneal injection, the three alkaloids were widely distributed in various tissues and organs, the spleen and pancreas were the most distributed, and the content of all tissues decreased significantly at 20minutes. Induction or inhibition of CYP3A4 in vivo can regulate the distribution and elimination effects of the three alkaloids in various tissues and organs. Additionally, induction of CYP3A4 can reduce the toxicity of humantenmine, and vice versa. Changes in CYP3A4 levels may account for the difference in toxicity of humantenmine. These findings provide a reliable and detailed dataset for drug interactions, tissue distribution, and toxicity studies of Gelsemium alkaloids.

Theoretical Insights into N-Glycoside Bond Cleavage of 5-Carboxycytosine by Thymine DNA Glycosylase: A QM/MM Study.

Thymine DNA glycosylase (TDG)-mediated excision of 5-formylcytosine and 5-carboxylcytosine (5-caC) is a critical step in active DNA demethylation. Herein, we employed a combined quantum mechanics/molecular mechanics approach to investigate the reaction mechanism of TDG-catalyzed N-glycosidic bond cleavage of 5-caC. The calculated results show that TDG-catalyzed 5-caC excision follows a concerted (SN2) mechanism in which glycosidic bond dissociation is coupled with nucleophile attack. Protonation of the 5-caC anion contributes to the cleavage of the N-glycoside bond, in which the N3-protonated zwitterion and imino tautomers are more favorable than carboxyl-protonated amino tautomers. This is consistent with the experimental data. Furthermore, our results reveal that the configuration rearrangement process of the protonated 5-caC would lower the stability of the N-glycoside bond and substantially reduce the barrier height for the subsequent C1'-N1 bond cleavage. This should be attributed to the smaller electrostatic repulsion between the leaving base and the negative phosphate group as a result of the structural rearrangement.

Genomic variation, environmental adaptation and feralization in ramie, an ancient fiber crop.

Feralization is an important evolutionary process, but the mechanisms behind it remain poorly understood. Here, we use the ancient fiber crop, ramie (Boehmeria nivea (L.) Gaudich.) as a model to investigate genomic changes associated with both domestication and fertilization. We first produced a chromosome-scale de novo genome assembly of feral ramie and investigated structural variations between feral and domesticated ramie genomes. Next, 915 accessions from 20 countries were gathered, comprising cultivars, major landraces, feral populations and wild progenitor. Based on whole genome resequencing of these accessions, the most comprehensive ramie genomic variation map to date was constructed. Phylogenetic, demographic, and admixture signal detection analyses indicate that feral ramie is of exoferal or exo-endo origin, i.e., descended from hybridization between domesticated ramie and wild progenitor or ancient landraces. Feral ramie has greater genetic diversity than wild or domesticated ramie, and genomic regions affected by natural selection during feralization are different from those under selection during domestication. Ecological analyses showed that feral and domesticated ramie have similar ecological niches which are substantially different from the niche of the wild progenitor, and three environmental variables were associated with habitat-specific adaptation in feral ramie. Our findings advance our understanding of feralization, providing a scientific basis for the excavation of new crop germplasm resources and offering novel insights into the evolution of feralization in nature.

Experimental Study on Tailings Deposition Distribution Pattern and Sedimentation Characteristics.

Tailings pond accidents frequently occur during an extended period, resulting in loss of life and property, wastage of resources, and environmental pollution. Relying on tailings pond engineering, this paper carried out sample particle fragmentation experiments and settling column experiments to explore the deposition distribution pattern of tailings in both horizontal and vertical directions as well as the impact of particle size distribution on the sedimentation stratification effect. The results show that the median particle size on the dry beach surface in the horizontal direction slowly decreased with the increase in the distance from the subdam. The particle size of tailings showed great fluctuations in the vertical direction, which gradually became finer with the increase in the depth overall. At the same time, saturated sedimentation experiments suggested the inconsistent variation rule with the field test, namely, coarse on the bottom and fine at the top, and the change in particle size greatly affected the tailing sedimentation stratification effect. With the increase in fine particle content in tailings, the appearance time of the water-sand interface was shortened to within 30 min, but the sedimentation and consolidation completion times were delayed to about 1400 min. The settling column results indicate that the increase in fine particle content gradually weakened the sedimentation stratification effect, and the sedimentation pattern transformed from independent sedimentation to floc-type average sedimentation, which led to the enhanced water-retaining property of the settled layer. This may lead to an increase in the saturation line and a decrease in the length of the dry beach, seriously affecting the safe operation of the tailings pond. The research results provide some theoretical guidance and basic data for analyzing the consolidation efficiency of tailings and the stability of the tailings pond.

An antioxidant hydrogel dressing with wound pH indication function prepared based on silanized bacterial nanocellulose crosslinked with beet red pigment extract.

Maintaining wound moisture and monitoring of infection are crucial aspects of chronic wound treatment. The development of a pH-sensitive functional hydrogel dressing is an effective approach to monitor, protect, and facilitate wound healing. In this study, beet red pigment extract (BRPE) served as a native and efficient pH indicator by being grafted into silane-modified bacterial nanocellulose (BNC) to prepare a pH-sensitive wound hydrogel dressing (S-g-BNC/BRPE). FTIR confirmed the successful grafting of BRPE into the BNC matrix. The S-g-BNC/BRPE showed superior mechanical properties (0.25 MPa), swelling rate (1251 % on average), and hydrophilic properties (contact angle 21.83°). The composite exhibited a notable color change as the pH changed between 4.0 and 9.0. It appeared purple-red when the pH ranged from 4.0 to 6.0, and appeared light pink at pH 7.0 and 7.4, and appeared ginger-yellow at pH 8.0 and 9.0. Subsequently, the antioxidant activity and cytotoxicity of the composite was evaluated, its DPPH·, ABTS+, ·OH scavenging rates were 32.33 %, 19.31 %, and 30.06 %, respectively, and the cytotoxicity test clearly demonstrated the safety of the dressing. The antioxidant hydrogel dressing, fabricated with a cost-effective and easy method, not only showed excellent biocompatibility and dressing performance but could also indicated the wound state based on pH changes.

Textured Perovskite/Silicon Tandem Solar Cells Achieving Over 30% Efficiency Promoted by 4-Fluorobenzylamine Hydroiodide.

Monolithic textured perovskite/silicon tandem solar cells (TSCs) are expected to achieve maximum light capture at the lowest cost, potentially exhibiting the best power conversion efficiency. However, it is challenging to fabricate high-quality perovskite films and preferred crystal orientation on commercially textured silicon substrates with micrometer-size pyramids. Here, we introduced a bulky organic molecule (4-fluorobenzylamine hydroiodide (F-PMAI)) as a perovskite additive. It is found that F-PMAI can retard the crystallization process of perovskite film through hydrogen bond interaction between F- and FA+ and reduce (111) facet surface energy due to enhanced adsorption energy of F-PMAI on the (111) facet. Besides, the bulky molecular is extruded to the bottom and top of perovskite film after crystal growth, which can passivate interface defects through strong interaction between F-PMA+ and undercoordinated Pb2+/I-. As a result, the additive facilitates the formation of large perovskite grains and (111) preferred orientation with a reduced trap-state density, thereby promoting charge carrier transportation, and enhancing device performance and stability. The perovskite/silicon TSCs achieved a champion efficiency of 30.05% based on a silicon thin film tunneling junction. In addition, the devices exhibit excellent long-term thermal and light stability without encapsulation. This work provides an effective strategy for achieving efficient and stable TSCs.

Latent profile analysis of depression in US adults with obstructive sleep apnea hypopnea syndrome.

Objective: This study used latent profile analysis to explore the level of depression among US adults with obstructive sleep apnea hypopnea syndrome (OSAHS) symptoms and to identify different latent categories of depression to gain insight into the characteristic differences between these categories. Methods: The data of this study were obtained from the National Health and Nutrition Examination Survey (NHANES) database, and the subjects with OSAHS symptoms were aged 18 years and older. The latent profile analysis (LPA) method was used to fit the latent depression categories in subjects with OSAHS symptoms. The chi-square test, rank sum test, and binary logistic regression were used to analyze the influencing factors of depression subgroups in subjects with OSAHS symptoms. Results: Three latent profiles were identified: low-level (83.7%), moderate-level (14.5%) and high-level (1.8%) depression. The scores of 9 items in the high-level depression group were higher than those in the other two groups. Among them, item 4 "feeling tired or lack of energy" had the highest score in all categories. Conclusion: Depression in subjects with OSAHS symptoms can be divided into low-level, moderate-level and high-level depression. There are significant differences among different levels of depression in gender, marital status, PIR, BMI, smoking, general health condition, sleep duration and OSAHS symptom severity.

Emerging trends of invasive yeast infections and azole resistance in Beijing intensive care units.

Invasive fungal infections pose a substantial threat to patients in healthcare settings globally. Recent changes in the prevalence of fungal species and challenges in conducting reference antifungal susceptibility testing emphasize the importance of monitoring fungi and their antifungal resistance. A two-phase surveillance project was conducted in Beijing, China, involving 37 centers across 12 districts, from January 2012 to December 2013 and from January 2016 to December 2017. We found that the proportion of Candida albicans in intensive care units (ICUs) during 2016-2017 exhibited a significant decline compared to the 2012-2013 period, although it remained the most predominant pathogen. In contrast, the prevalence of Nakaseomyces glabratus (formerly Candida glabrata) and Candida tropicalis notably increased during the two-phase surveillance. The high prevalence of C. tropicalis and its resistance to azole drugs posed a serious threat to patients in ICUs. The pathogens causing invasive fungal infections in Beijing were relatively sensitive to echinocandins. While C. albicans continued to exhibit susceptibility to azoles, the resistance and growth rates of C. tropicalis towards azoles were particularly prominent. Concerns were raised due to the emergence of multiple, short-term isolates of Clavispora lusitaniae and Candida parapsilosis complex in neonatal ICUs, given their similarity in antifungal susceptibilities. Such occurrences point towards the potential for transmission and persisting presence of these pathogens within the ICU environment. Our study complements existing data on the epidemiology of invasive fungal infections. It is imperative to exercise cautious medication management for ICU patients in Beijing, paying particular attention to azole resistance in C. tropicalis.

Effective immobilization and biosafety assessment of antimony in soil with zeolite-supported nanoscale zero-valent iron.

Antimony (Sb) contamination in certain areas caused by activities such as antimony mining and smelting poses significant risks to human health and ecosystems. In this study, a stable composite material consisting of natural zeolite-supported nanoscale zero-valent iron (Z-ZVI) was successfully prepared. The immobilization effect of Z-ZVI on Sb in contaminated soil was investigated. Experimental results showed that Z-ZVI exhibited superior performance compared to pure nano zero-valent iron (nZVI) in terms of stability, with a lower zeta potential (-25.16 mV) at a pH of 7 and a higher specific surface area (54.54 m2/g). It can be easily applied and dispersed in contaminated soils. Additionally, Z-ZVI demonstrated a more abundant porous structure. After 60 days of treatment with 3% Z-ZVI, the leaching concentration of Sb in the contaminated soil decreased from 1.32 mg/L to 0.31 mg/L (a reduction of 76%), and the concentration of available Sb species decreased from 19.84 mg/kg to 0.71 mg/kg, achieving a fixation efficiency of up to 90%. X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) analysis confirmed the effective immobilization of Sb in the soil through reduction of antimonate to antimonite, precipitation, and adsorption processes facilitated by Z-ZVI. Moreover, the addition of Z-ZVI effectively reduced the bioavailability of Sb in the contaminated soil, thereby mitigating its toxicity to earthworms. In conclusion, Z-ZVI can be utilized as a promising material for the safe remediation and antimony and other heavy metal-contaminated soils.

PD-L1 blockade in mitigating severe acute pancreatitis induced pancreatic damage through modulation of immune cell apoptosis.

Acute pancreatitis (AP) is a prevalent gastrointestinal disorder. The immune response plays a crucial role in AP progression. However, the impact of immune regulatory checkpoint PD-L1 on severe acute pancreatitis (SAP) remains uncertain. Hence, this study aimed to examine the influence of PD-L1 on SAP. We assessed PD-L1 expression in neutrophils and monocytes obtained from SAP patients. We induced SAP in C57BL/6J mice, PD-L1 gene-deficient mice, and PD-L1 humanized mice using intraperitoneal injections of cerulein plus lipopolysaccharide. Prior to the initial cerulein injection, a PD-L1 inhibitor was administered. Pancreatic tissues were collected for morphological and immunohistochemical evaluation, and serum levels of amylase, lipase, and cytokines were measured. Flow cytometry analysis was performed using peripheral blood cells. The expression of PD-L1 in neutrophils and monocytes was significantly higher in SAP patients compared to healthy individuals. Likewise, the expression of PD-L1 in inflammatory cells in the peripheral blood of SAP-induced C57BL/6J mice was notably higher than in the control group. In mice with PD-L1 deficiency, SAP model exhibited lower pancreatic pathology scores, amylase, lipase, and cytokine levels compared to wild-type mice. PD-L1 deletion resulted in reduced neutrophil apoptosis, leading to an earlier peak in neutrophil apoptosis. Furthermore, it decreased early monocyte apoptosis and diminished the peak of T lymphocyte apoptosis. Within the SAP model, administration of a PD-L1 inhibitor reduced pancreatic pathology scores, amylase, lipase, and cytokine levels in both C57BL/6J mice and PD-L1 humanized mice. These findings suggest that inhibiting PD-L1 expression can alleviate the severity of SAP.

Bisphenol S impairs mitochondrial function by targeting Myo19/oxidative phosphorylation pathway contributing to axonal and dendritic injury.

Exposure to bisphenol S (BPS) is known to adversely affect neuronal development. As pivotal components of neuronal polarization, axons and dendrites are indispensable structures within neurons, crucial for the maintenance of nervous system function. Here, we investigated the impact of BPS exposure on axonal and dendritic development both in vivo and in vitro. Our results revealed that exposure to BPS during pregnancy and lactation led to a reduction in the complexity, density, and length of axons and dendrites in the prefrontal cortex (PFC) of offspring. Employing RNA sequencing technology to elucidate the underlying mechanisms of axonal and dendritic damage induced by BPS, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted a significant alteration in the oxidative phosphorylation (OXPHOS) pathway, essential for mitochondrial function. Subsequent experiments demonstrate BPS-induced impairment in mitochondrial function, including damaged morphology, decreased adenosine triphosphate (ATP) and superoxide dismutase (SOD) levels, and increased reactive oxygen species and malondialdehyde (MDA). These alterations coincided with the downregulated expression of OXPHOS pathway-related genes (ATP6V1B1, ATP5K, NDUFC1, NDUFC2, NDUFA3, COX6B1) and Myosin 19 (Myo19). Notably, Myo19 overexpression restored the BPS-induced mitochondrial dysfunction by alleviating the inhibition of OXPHOS pathway. Consequently, this amelioration was associated with a reduction in BPS-induced axonal and dendritic injury observed in cultured neurons of the PFC.

Microplastics shaped performance, microbial ecology and community assembly in simultaneous nitrification, denitrification and phosphorus removal process.

The widespread use of microplastics (MPs) has led to an increase in their discharge to wastewater treatment plants. However, the knowledge of impact of MPs on macro-performance and micro-ecology in simultaneous nitrification, denitrification, and phosphorus removal (SNDPR) systems is limited, hampering the understanding of potential risks posed by MPs. This study firstly comprehensively investigated the performance, species interactions, and community assembly under polystyrene (PS) and polyvinyl chloride (PVC) exposure in SNDPR systems. The results showed under PS (1, 10 mg/L) and PVC (1, 10 mg/L) exposure, total nitrogen removal was reduced by 3.38-10.15 %. PS and PVC restrained the specific rates of nitrite and nitrate reduction (SNIRR, SNRR), as well as the activities of nitrite and nitrate reductase enzymes (NIR, NR). The specific ammonia oxidation rate (SAOR) and activity of ammonia oxidase enzyme (AMO) were reduced only at 10 mg/L PVC. PS and PVC enhanced the size of co-occurrence networks, niche breadth, and number of key species while decreasing microbial cooperation by 5.85-13.48 %. Heterogeneous selection dominated microbial community assembly, and PS and PVC strengthened the contribution of stochastic processes. PICRUSt prediction further revealed some important pathways were blocked by PS and PVC. Together, the reduced TN removal under PS and PVC exposure can be attributed to the inhibition of SAOR, SNRR, and SNIRR, the restrained activities of NIR, NR, and AMO, the changes in species interactions and community assembly mechanisms, and the suppression of some essential metabolic pathways. This paper offers a new perspective on comprehending the effects of MPs on SNDPR systems.

Simultaneous Enhancement of Strength and Sulfide Stress Cracking Resistance of Hot-Rolled Pressure Vessel Steel Q345 via a Quenching and Tempering Treatment.

Sulfide stress cracking (SSC) failure is a main concern for the pressure vessel steel Q345 used in harsh sour oil and gas environments containing hydrogen sulfide (H2S). Methods used to improve the strength of steel usually decrease their SSC resistance. In this work, a quenching and tempering (Q&T) processing method is proposed to provide higher strength combined with better SSC resistance for hot-rolled Q345 pressure vessel steel. Compared to the initial hot-rolled plates having a yield strength (YS) of ~372 MPa, the Q&T counterparts had a YS of ~463 MPa, achieving a remarkable improvement in the strength level. Meanwhile, there was a resulting SSC failure in the initial hot-rolled plates, which was not present in the Q&T counterparts. The SSC failure was not only determined by the strength. The carbon-rich zone, residual stress, and sensitive hardness in the banded structure largely determined the susceptibility to SSC failure. The mechanism of the property amelioration might be ascribed to microstructural modification by the Q&T processing. This work provides an approach to develop improved strength grades of SSC-resistant pressure vessel steels.

Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population.

BACKGROUND: Colorectal cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. Syndecan-2 methylation (mSDC2) testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. Cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. AIM: To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China. METHODS: A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing. Sensitivity and specificity for CRC, advanced adenoma (AA) and advanced colorectal neoplasia (ACN) were determined. High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test. RESULTS: A total of 1035 high-risk individuals were included in this study according to established criteria. Among them, 16 suffered from CRC (1.55%), 65 from AA (6.28%) and 189 from non-AAs (18.26%); 150 patients were diagnosed with polyps (14.49%). Diagnoses were established based upon colonoscopic and pathological examinations. Sensitivities of the mSDC2 test for CRC and AA were 87.50% and 40.00%, respectively; specificities were 95.61% for other groups. Positive predictive values of the mSDC2 test for CRC, AA and ACN were 16.09%, 29.89% and 45.98%, respectively; the negative predictive value for CRC was 99.79%. After adjusting for other high-risk covariates, mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN (P < 0.001). CONCLUSION: Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

Multivariate modular metabolic engineering and medium optimization for vitamin B12 production by Escherichia coli.

Vitamin B12 is a complex compound synthesized by microorganisms. The industrial production of vitamin B12 relies on specific microbial fermentation processes. E. coli has been utilized as a host for the de novo biosynthesis of vitamin B12, incorporating approximately 30 heterologous genes. However, a metabolic imbalance in the intricate pathway significantly limits vitamin B12 production. In this study, we employed multivariate modular metabolic engineering to enhance vitamin B12 production in E. coli by manipulating two modules comprising a total of 10 genes within the vitamin B12 biosynthetic pathway. These two modules were integrated into the chromosome of a chassis cell, regulated by T7, J23119, and J23106 promoters to achieve combinatorial pathway optimization. The highest vitamin B12 titer was attained by engineering the two modules controlled by J23119 and T7 promoters. The inclusion of yeast powder to the fermentation medium increased the vitamin B12 titer to 1.52 mg/L. This enhancement was attributed to the effect of yeast powder on elevating the oxygen transfer rate and augmenting the strain's isopropyl-ß-d-1-thiogalactopyranoside (IPTG) tolerance. Ultimately, vitamin B12 titer of 2.89 mg/L was achieved through scaled-up fermentation in a 5-liter fermenter. The strategies reported herein will expedite the development of industry-scale vitamin B12 production utilizing E. coli.

Alloying Driven Antiferromagnetic Skyrmions on NiPS3 Monolayer: A First-Principles Calculation.

Topological magnetic states are promising information carriers for ultrahigh-density and high-efficiency magnetic storage. Recent advances in two-dimensional (2D) magnets provide powerful platforms for stabilizing various nanometer-size topological spin textures within a wide range of magnetic field and temperature. However, non-centrosymmetric 2D magnets with broken inversion symmetry are scarce in nature, making direct observations of the chiral spin structure difficult, especially for antiferromagnetic (AFM) skyrmions. In this work, it is theoretically predicted that intrinsic AFM skyrmions can be easily triggered in XY-type honeycomb magnet NiPS3 monolayer by alloying of Cr atoms, due to the presence of a sizable Dzyaloshinskii-Moriya interaction. More interestingly, the diameter of the AFM skyrmions in Ni3/4Cr1/4PS3 decreases from 12 to 4.4 nm as the external magnetic field increases and the skyrmion phases remain stable up to an external magnetic field of 4 T. These results highlight an effective strategy to generate and modulate the topological spin texture in 2D magnets by alloying with magnetic element.

Hb H disease associated with compound heterozygosity for --SEA deletion and a novel alpha globin chain variant (HBA2:c.175C>A) on the distal histidine in a Chinese family.

OBJECTIVES: In clinical practice, the majority of α-thalassaemia cases arise from deletions of the α-globin genes. However, a subset of cases is attributed to rare haemoglobin variants, which can manifest with borderline or normal screening results, potentially leading to missed diagnoses in clinical practice. METHODS: Blood samples were collected from family members and underwent haematological, DNA and RNA analysis. RESULTS: The five-month-old proband presented a haematological phenotype consistent with Hb H disease. The mother's haematology profile was consistent with an α-thalassaemia carrier, while the father exhibited a borderline reduction in MCV and MCH. MALDI-TOF identified an abnormal α-chain in the proband. DNA analysis revealed a novel α-globin variant (HBA2:c.175C>A, α58His>Asn, Hb DG-Nancheng) affecting the distal histidine in the family. The father and the mother had α-genotype of --SEA/αα and αDG-Nanchengα/αα, respectively; while the proband inherited both mutant alleles (--SEA/αDG-Nanchengα). Sequencing of cDNA from HBA2 gene identified an equal ratio of normal and mutant alleles. CONCLUSION: This rare case highlighted the importance of identifying rare haemoglobin variant during prenatal screening. The clinical and genetic data provides useful information on the pathogenicity of this variant and further insight into the role of distal histidine residue of α-globin.

Genome-wide analysis of in vivo-evolved Candida auris reveals multidrug-resistance mechanisms.

Candida auris, an emerging and multidrug-resistant fungal pathogen, has led to numerous outbreaks in China. While the resistance mechanisms against azole and amphotericin B have been studied, the development of drug resistance in this pathogen remains poorly understood, particularly in in vivo-generated drug-resistant strains. This study employed pathogen whole-genome sequencing to investigate the epidemiology and drug-resistance mutations of C. auris using 16 strains isolated from two patients. Identification was conducted through Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and antimicrobial susceptibilities were assessed using broth microdilution and Sensititre YeastOne YO10. Whole-genome sequencing revealed that all isolates belonged to the South Asian lineage, displaying genetic heterogeneity. Despite low genetic variability among patient isolates, notable mutations were identified, including Y132F in ERG11 and A585S in TAC1b, likely linked to increased fluconazole resistance. Strains from patient B also carried F214L in TAC1b, resulting in a consistent voriconazole minimum inhibitory concentration of 4 µg/mL across all isolates. Furthermore, a novel frameshift mutation in the SNG1 gene was observed in amphotericin B-resistant isolates compared to susceptible ones. Our findings suggest the potential transmission of C. auris and emphasize the need to explore variations related to antifungal resistance. This involves analyzing genomic mutations and karyotypes, especially in vivo, to compare sensitive and resistant strains. Further monitoring and validation efforts are crucial for a comprehensive understanding of the mechanisms of drug resistance in C. auris.