Toxic mechanism in Daphnia magna due to phthalic acid esters and CuO nanoparticles co-exposure: The insight of physiological, microbiomic and metabolomic profiles.

Various phthalic acid esters (PAEs) such as dibutyl phthalate (DBP) and butyl benzyl phthalate (BBP) co-exist with nanopollutants in aquatic environment. In this study, Daphnia magna was exposed to nano-CuO and DBP or BBP at environmental relevant concentrations for 21-days to investigate these combined toxic effects. Acute EC50 values (48 h) of nano-CuO, DBP, and BBP were 12.572 mg/L, 8.978 mg/L, and 4.785 mg/L, respectively. Results showed that co-exposure with nano-CuO (500 µg/L) for 21 days significantly enhanced the toxicity of DBP (100 µg/L) and BBP (100 µg/L) to Daphnia magna by 18.37% and 18.11%, respectively. The activities of superoxide dismutase, catalase, and glutathione S-transferase were enhanced by 10.95% and 14.07%, 25.63% and 25.91%, and 39.93% and 35.01% in nano-CuO+DBP and nano-CuO+BBP treatments as compared to the individual exposure groups, verifying that antioxidative defense responses were activated. Furthermore, the co-exposure of nano-CuO and PAEs decreased the population richness and diversity microbiota, and changed the microbial community composition in Daphnia magna. Metabolomic analysis elucidated that nano-CuO + PAEs exposure induced stronger disturbance on metabolic network and molecular function, including amino acid, nucleotides, and lipid metabolism-related metabolic pathways, as comparison to PAEs single exposure treatments. In summary, the integration of physiological, microflora, and untargeted metabolomics analysis offers a fresh perspective into the potential ecological risk associated with nanopollutants and phthalate pollution in aquatic ecosystems.

High-Performance Thin-Layer Chromatography Coupled with Single Quadrupole: Application the Identification and Differentiation of Rehmanniae Radix and Its Different Processing Products from Raw Materials to Commercial Products.

The authentication of ingredients in formulas is crucial yet challenging, particularly for constituents with comparable compositions but vastly divergent efficacy. Rehmanniae Radix and its derivatives are extensively utilized in food supplements, which contain analogous compositions but very distinct effects. Rehmanniae Radix, also a difficult-to-detect herbal ingredient, was chosen as a case to explore a novel HPTLC-QDa MS technique for the identification of herbal ingredients in commercial products. Through systematic condition optimization, including thin layer and mass spectrometry, a stable and reproducible HPTLC-QDa MS method was established, which can simultaneously detect oligosaccharides and iridoids. Rehmannia Radix and its processed products were then analyzed to screen five markers that could distinguish between raw and prepared Rehmannia Radix. An HPTLC-QDa-SIM method was further established for formula detection by using the five markers and validated using homemade prescriptions and negative controls. Finally, this method was applied to detect raw and prepared Rehmannia Radix in 12 commercial functional products and supplements.

Genome-wide identification of JAZ gene family in sugarcane and function analysis of ScJAZ1/2 in drought stress response and flowering regulation.

The JASMONATE ZIM DOMAIN (JAZ) proteins are a key inhibitors of the jasmonic acid (JA) signaling pathway that play an important role in the regulation of plant growth and development and environmental stress responses. However, there is no systematic identification and functional analysis of JAZ gene family members in sugarcane. In this study, a total of 49 SsJAZ genes were identified from the wild sugarcane species Saccharum spontaneum genome that were unevenly distributed on 13 chromosomes. Phylogenetic analysis showed that all SsJAZ members can be divided into six groups, and most of the SsJAZ genes contained photoreactive and ABA-responsive elements. RNA-seq analysis revealed that SsJAZ1-1/2/3/4 and SsJAZ7-1 were significantly upregulated under drought stress. The transcript level of ScJAZ1 which is the homologous gene of SsJAZ1 in modern sugarcane cultivars was upregulated by JA, PEG, and abscisic acid (ABA). Moreover, ScJAZ1 can interact with three other JAZ proteins to form heterodimers. The spatial and temporal expression analysis showed that SsJAZ2-1/2/3/4 were highly expressed in different tissues and growth stages and during the day-night rhythm between 10:00 and 18:00. Overexpression of ScJAZ2 in Arabidopsis accelerated flowering through activating the expression of AtSOC1, AtFT, and AtLFY. Moreover, the transcription level of ScJAZ2 was about 30-fold in the early-flowering sugarcane variety than that of the non-flowering variety, indicating ScJAZ2 positively regulated flowering. This first systematic analysis of the JAZ gene family and function analysis of ScJAZ1/2 in sugarcane provide key candidate genes and lay the foundation for sugarcane breeding.

Transport and risk of airborne pathogenic microorganisms in the process of decentralized sewage discharge and treatment.

Sewage treatment processes are a critical anthropogenic source of bioaerosols and may present significant health risks to plant workers. Compared with the specialization and scale of urban sewage treatment, many decentralized treatment models are flexible and extensive. These treatment facilities are usually close to residential areas owing to the pipe network layout and other restrictions. Bioaerosols generated by these facilities may present a serious and widespread occupational and non-occupational exposure risk to nearby residents, particularly the elderly and children. An understanding of the characteristics and exposure risks of bioaerosols produced during decentralized sewage treatment is lacking. We compared bioaerosol emission characteristics and potential exposure risks under four decentralized sewage discharge methods and treatment models: small container collection (SCC), open-channel discharge (OCD), single household/combined treatment (SHCT), and centralized treatment (CT) in northwest China. The OCD mode had the highest bioaerosol production, whereas the CT mode had the lowest. The OCD model contained the most pathogenic bacterial species, up to 43 species, including Sphingomonas, Pseudomonas, Cladosporium, and Alternaria. Risk assessments indicated bioaerosol exposure was lower in the models with sewage treatment (SHCT and CT) than in those without (SCC and OCD). Different populations exhibited large variations in potential risks owing to differences in time spent indoors and outdoors. The highest risk was observed in males exposed to the SCC model. This study provides a theoretical basis and theories for the future joint prevention and control of the bioaerosol exposure risk from decentralized sewage treatment.

The feasibility of dexmedetomidine-led anesthesia maintenance strategy during major abdominal surgery.

Background: Dexmedetomidine is known for its selective action on α2-adrenoceptor sites and is recognized for its neuroprotective capabilities. It can improve postoperative cognitive function. Commonly used anesthetics, such as sevoflurane and propofol, have been reported to affect postoperative cognitive function. Therefore, it could be valuable to explore dexmedetomidine-led anesthesia strategy. This study was designed to assess the performance, safety, and effective infusion rate in anesthesia maintenance, to explore a feasible dexmedetomidine-led anesthesia maintenance protocol, and to provide a foundation for potential combined anesthesia. Methods: Thirty patients aged 18-60 years, classified as ASA I or II, undergoing abdominal surgery were involved. The anesthesia maintenance was achieved with dexmedetomidine, remifentanil and rocuronium. Dixon up-and-down sequential methodology was utilized to ascertain the ED50 of dexmedetomidine for maintaining Patient State Index (PSI) 25-40 (depth of stage III anesthesia). Intraoperative HR, BP and depth of anesthesia were monitored and controlled. The wake-up time from anesthesia, the incidence of intraoperative awareness and postoperative delirium, and the patients' satisfaction were assessed. Results: The results indicated that dexmedetomidine-led anesthesia could maintain the depth of stage III anesthesia during abdominal surgery. The ED50 and ED95 of dexmedetomidine infusion rates during anesthesia maintenance were 2.298 µg/kg·h (95%CI: 2.190-2.404 µg/kg·h) and 3.765 µg/kg·h (95%CI: 3.550-4.050 µg/kg·h). Continuous infusion of dexmedetomidine and 0.1-0.3 µg/kg·min remifentanil could maintain PSI 25-40, and provide appropriate anesthesia depth for abdominal surgery. Perioperative bradycardia and hypertension could be rapidly corrected with atropine and nitroglycerin. The median wake-up time after anesthesia was 4.8 min, the perioperative maximum HR had significant correlation with wake-up time and intraoperative dexmedetomidine dose. No intraoperative awareness and postoperative delirium occurred; the patients were satisfied with dexmedetomidine-led anesthesia. Conclusions: dexmedetomidine-led strategy could maintain stable depth of anesthesia throughout surgery, and the ED50 of dexmedetomidine infusion rates was 2.298 µg/kg·h. Intraoperative HR, BP and depth of anesthesia require monitoring, the bradycardia and hypertension could be rapidly corrected.

Hand skeletal features of children and adolescents with different growth statuses and periods.

Background: The hand skeletal features of children and adolescents at different growth statuses and development periods, and the correlation between these skeletal features and hand asymmetric force are currently unclear. Thus, this study sought to investigate the hand skeletal features of children and adolescents at different growth statuses and at different periods of development, and the correlation between these skeletal features and asymmetric force in hands. Methods: A retrospective study was performed on subjects aged 4-20 years with good growth status (group A) or short stature (group B). Additional subjects aged 4-20, 21-40, and >40 years were enrolled in groups C, D, and E, respectively. All the subjects underwent left-hand posteroanterior X-ray radiography. Brachymesophalangia-V (BMP-V), conical epiphysis, epiphysis/metaphysis symmetry of the proximal phalanx (ESP), and the angle of the metacarpal-phalangeal axis were analyzed. Results: Of the 654 children and teenagers aged 4-20 years (median: 11 years) enrolled in the study, 432 were allocated to group A, of whom 237 (54.9%) were male and 195 (45.1%) were female, and 222 matched cases were allocated to group B, of whom 112 (50.5%) were male and 110 (49.5%) were female. The first to third ESPs were significantly (P<0.05) greater in group A than in group B, while the first to third angles of the metacarpal-phalangeal axis were significantly (P<0.05) smaller in group A than in group B. The correlation analysis revealed a highly significant (P<0.01) negative correlation between the ESP and angle of the metacarpal-phalangeal axis (r=-0.948, -0.926, -0.940, -0.885, and -0.848, respectively). The incidence of BMP-V was 15.4% in all patients, while that of conical epiphysis was 19.5%. The incidence of BMP-V and conical epiphysis was significantly (P<0.05) smaller in group A than in group B (11.1% vs. 23.8% for BMP-V and 16.6% vs. 25.2% for conical epiphysis, respectively). Additionally, 216 subjects were enrolled in group C (108 male and 108 female), 185 subjects were enrolled in in group D (93 male and 92 female), and 176 subjects were enrolled in in group E (104 male and 72 female). The second to fifth ESPs in group C were significantly (P<0.05) smaller than those in both groups D and E, while the second to fifth angles of the metacarpal-phalangeal axis were significantly (P<0.05) larger in group C than in both groups D and E. A BMP-V was present in 35 (16.2%) patients in group C, 8 (4.3%) in group D, and 2 (1.1%) in group E, and the difference among the three groups was statistically significant (P<0.05). Conclusions: The epiphyseal symmetry of the proximal phalanges is poor in short stature children and adolescents, and the angle between the metacarpal and phalangeal axes is larger in children and adolescents with short stature than those with normal height and good growth status. A negative correlation was found between the epiphyseal symmetry of the proximal phalanges and asymmetrical stress.

Ionized water-soluble organic nanosheets with light/ultrasound dual excitation channels for efficient killing of multidrug-resistant bacteria.

A novel ionized heavy-atom-free two-dimensional organic nanosheet was prepared and exhibited highly selective generation of singlet oxygen under both light and ultrasound excitation. These ionized nanosheets displayed excellent dispersibility in water and enhanced singlet oxygen production efficiency compared to their non-assembled monomers. Antimicrobial experiments have revealed their potent bactericidal effects on drug-resistant E. coli and S. aureus under both visible light and ultrasound irradiation.

Metabolite and protein shifts in mature erythrocyte under hypoxia.

As the only cell type responsible for oxygen delivery, erythrocytes play a crucial role in supplying oxygen to hypoxic tissues, ensuring their normal functions. Hypoxia commonly occurs under physiological or pathological conditions, and understanding how erythrocytes adapt to hypoxia is fundamental for exploring the mechanisms of hypoxic diseases. Additionally, investigating acute and chronic mountain sickness caused by plateaus, which are naturally hypoxic environments, will aid in the study of hypoxic diseases. In recent years, increasingly developed proteomics and metabolomics technologies have become powerful tools for studying mature enucleated erythrocytes, which has significantly contributed to clarifying how hypoxia affects erythrocytes. The aim of this article is to summarize the composition of the cytoskeleton and cytoplasmic proteins of hypoxia-altered erythrocytes and explore the impact of hypoxia on their essential functions. Furthermore, we discuss the role of microRNAs in the adaptation of erythrocytes to hypoxia, providing new perspectives on hypoxia-related diseases.

Interference-induced generation of a chirp-free short isolated attosecond pulse in the water window region with multicolor laser fields.

Compensating for the intrinsic attosecond chirp (atto-chirp) of wideband high-order harmonics in the water window region is a significant challenge, in order to obtain isolated attosecond pulses (IAPs) with a width of tens of attoseconds (as). Here, we propose to realize the generation of IAP with duration as short as 20 as, central energy of 365 eV, and bandwidth exceeding 150 eV from chirp-free high harmonics generated by a four-color driving laser, without the necessity for atto-chirp compensation with natural materials. Unlike any other gating methods that an IAP arises from only one electron ionization event, we take advantage of the interference between harmonic radiation produced by multiple ionizing events. We further demonstrate that such chirp-free short IAP survives after taking account of macroscopic propagation effects. Given that the synthesized multicolor laser field can also effectively increase the harmonic flux, this work provides a practical way for experiments to generate the broad bandwidth chirp-free IAPs in the water window region.

Deficiency of peripheral CLA+ Tregs and clinical relevance in Behcet's syndrome.

BACKGROUND: Autoimmune responses have been suggested to involvement in patients with Behcet's syndrome (BS). There has been growing attention towards the roles of cutaneous lymphocyte antigen (CLA)+ regular T cells (Tregs) in autoimmune diseases. The role of CLA+ Tregs in BS is still uncertain. This study aims to clarify the impact of CLA+ Tregs on BS. METHODS: We collected peripheral blood from a total of 107 patients with BS and 114 healthy controls (HCs). The number of CLA+ Tregs, natural killer (NK) cells, B cells, and several subtypes of CD4+ T cells were detected using flow cytometry and compared between patients and HCs. RESULTS: The absolute number and proportion of CLA+ Tregs among CD4+ T lymphocytes and CD4+ Tregs were lower in patients with BS than in HCs. CLA+ Tregs were positively related with NK cells (r = 0.500, P < 0.001) and B cells (r = 0.470, P < 0.001) and negatively related with effector T cells (r=-0.402, P < 0.001) in patients with BS. Patients with BS and arterial aneurysms had CLA+ Treg cell deficiency. A decreased proportion of CLA+ Tregs was associated with arterial aneurysms in patients with BS. The proportion of CLA+ Tregs in patients with BS increased with corticosteroids and immunosuppressants. CONCLUSION: CLA+ Tregs decrease in association with arterial aneurysm in patients with BS. CLA+ Tregs may be a predictor of response to BS treatment.

An N-Shaped Lightweight Network with a Feature Pyramid and Hybrid Attention for Brain Tumor Segmentation.

Brain tumor segmentation using neural networks presents challenges in accurately capturing diverse tumor shapes and sizes while maintaining real-time performance. Additionally, addressing class imbalance is crucial for achieving accurate clinical results. To tackle these issues, this study proposes a novel N-shaped lightweight network that combines multiple feature pyramid paths and U-Net architectures. Furthermore, we ingeniously integrate hybrid attention mechanisms into various locations of depth-wise separable convolution module to improve efficiency, with channel attention found to be the most effective for skip connections in the proposed network. Moreover, we introduce a combination loss function that incorporates a newly designed weighted cross-entropy loss and dice loss to effectively tackle the issue of class imbalance. Extensive experiments are conducted on four publicly available datasets, i.e., UCSF-PDGM, BraTS 2021, BraTS 2019, and MSD Task 01 to evaluate the performance of different methods. The results demonstrate that the proposed network achieves superior segmentation accuracy compared to state-of-the-art methods. The proposed network not only improves the overall segmentation performance but also provides a favorable computational efficiency, making it a promising approach for clinical applications.

Unveiling the significance of TREM1/2 in hemorrhagic stroke: structure, function, and therapeutic implications.

Stroke has long been a major threat to human health worldwide. Hemorrhagic stroke, including intracerebral hemorrhage and subarachnoid hemorrhage, exhibits a high incidence rate and a high mortality and disability rate, imposing a substantial burden on both public health and the economy and society. In recent years, the triggering receptor expressed on myeloid cells (TREM) family has garnered extensive attention in various pathological conditions, including hemorrhagic stroke. This review comprehensively summarizes the structure and function of TREM1/2, as well as their roles and potential mechanisms in hemorrhagic stroke, with the aim of providing guidance for the development of targeted therapeutic strategies in the future.

Superaerophilic/Superaerophobic NiFe-LDHs Electrode for Enhancing Overall Water Splitting in Alkaline Media.

Overall water splitting, as a critical approach to producing green hydrogen, is greatly impeded by the mass transfer of gaseous bubbles and dissolved gas molecules. Herein, a bifunctional superaerophilic/superaerophobic (SAL/SAB) NiFe layered-double-hydroxides (LDHs) electrode has been developed, which can drive H2 and O2 bubbles out of the reaction system by asymmetric Laplace pressure and accelerate dissolved gases diffusion through reducing their diffusion distance. Consequently, the SAL/SAB NiFe-LDHs electrode exhibits excellent HER activity with an overpotential of -76 mV at -10 mA cm-2 and outstanding oxygen evolution reaction activity with an overpotential of 253 mV at 100 mA cm-2. The bifunctional SAL/SAB NiFe-LDHs electrode is further utilized in overall water splitting, which can achieve 10 mA cm-2 with a cell voltage of 1.54 V. This work provides an efficient strategy to improve the efficiency of overall water splitting and can stimulate new electrode design in various gas-involved processes.

Reconstitution of RNA cap methylation reveals different features of SARS-CoV-2 and SARS-CoV methyltransferases.

Cap RNA methylations play important roles in the replication, evasion of host RNA sensor recognition, and pathogenesis. Coronaviruses possess both guanine N7- and 2'-O-ribose methyltransferases (N7-MTase and 2'-O-MTase) encoded by nonstructural protein (nsp) 14 and nsp16/10 complex, respectively. In this study, we reconstituted the two-step RNA methylations of N7-MTase and 2'-O-MTase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and demonstrated its common and different features in comparison with that of SARS-CoV. We revealed that the nsp16/10 2'-O-MTase of SARS-CoV-2 has a broader substrate selectivity than the counterpart of SARS-CoV and can accommodate both unmethylated and uncapped RNA substrates in a sequence-independent manner. Most intriguingly, the substrate selectivity of nsp16/10 complex is not determined by the apoenzyme of nsp16 MTase but by its cofactor nsp10. These results provide insight into the unique features of SARS-CoV-2 MTases and may help develop strategies to precisely intervene in the methylation pathway and pathogenesis of SARS-CoV-2.

Characterization of Four Complete Mitogenomes of Monolepta Species and Their Related Phylogenetic Implications.

Monolepta is one of the diverse genera in the subfamily Galerucinae, including 708 species and 6 sub-species worldwide. To explore the information on the mitogenome characteristics and phylogeny of the section "Monoleptites", especially the genus Monolepta, we obtained the newly completed mitochondrial genomes (mitogenomes) of four Monolepta species using high-throughput sequencing technology. The lengths of these four new mitochondrial genomes are 16,672 bp, 16,965 bp, 16,012 bp, and 15,866 bp in size, respectively. All four mitochondrial genomes include 22 transfer RNA genes (tRNAs), 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNAs), and one control region, which is consistent with other Coleoptera. The results of the nonsynonymous with synonymous substitution rates showed that ND6 had the highest evolution rate, while COI displayed the lowest evolution rate. The substitution saturation of three datasets (13 PCGs_codon1, 13 PCGs_codon2, 13 PCGs_codon3) showed that there was no saturation across all datasets. Phylogenetic analyses based on three datasets (ND1, 15 genes of mitogenomes, and 13 PCGs_AA) were carried out using maximum likelihood (ML) and Bayesian inference (BI) methods. The results showed that mitogenomes had a greater capacity to resolve the main clades than the ND1 gene at the suprageneric and species levels. The section "Monoleptites" was proven to be a monophyletic group, while Monolepta was a non-monophyletic group. Based on ND1 data, the newly sequenced species whose antennal segment 2 was shorter than 3 were split into several clades, while, based on the mitogenomic dataset, the four newly sequenced species had close relationships with Paleosepharia. The species whose antennal segment 2 was as long as 3 were split into two clades, which indicated that the characteristic of "antennal segment 2 as long as 3" of the true "Monolepta" evolved multiple times in several subgroups. Therefore, to explore the relationships among the true Monolepta, the most important thing is to perform a thorough revision of Monolepta and related genera in the future.

Effects of small-dose S-ketamine on anesthesia-induced atelectasis in patients undergoing general anesthesia accessed by lung ultrasound: study protocol for a randomized, double-blinded controlled trial.

BACKGROUND: Atelectasis after anesthesia induction in most patients undergoing general anesthesia may lead to postoperative pulmonary complications (PPCs) and affect postoperative outcomes. However, there is still no existing effective method used for the prevention of perioperative atelectasis. S-ketamine may prevent atelectasis due to airway smooth muscle relaxation and anti-inflammatory effects. Lung ultrasound is a portable and reliable bedside imaging technology for diagnosing anesthesia-induced atelectasis. The primary objective of this study is to assess whether a small dose of S-ketamine can reduce the incidence of atelectasis after intubation, and further investigate the effects of preventing the early formation of perioperative atelectasis and PPCs. METHODS: This is a single-institution, prospective, randomized controlled, parallel grouping, and double-blind study. From October 2020 to March 2022, 100 patients (18-60 years old) scheduled for elective surgery will be recruited from Beijing Tiantan Hospital, Capital Medical University, and randomly assigned to the S-ketamine group (group 1) and the normal saline group (group 2) at a ratio of 1:1. The label-masked agents will be administered 5 min before induction, and all patients will undergo a standardized general anesthesia protocol. Related data will be collected at three time points: after radial artery puncture (T1), 15 min after tracheal intubation (T2), and before extubation (T3). The primary outcome will be the total lung ultrasound scores (LUS) at T2. Secondary outcomes will include LUS in six chest regions at T2, total LUS at T3, arterial blood gas analysis results (PaCO2, PaO2) and PaO2/FiO2 at T2 and T3, and plateau pressure (Pplat) and dynamic lung compliance (Cdyn) at T2 and T3. The incidence of postoperative complications associated with S-ketamine and PPCs at 2 h and 24 h after surgery will be recorded. DISCUSSION: This trial aims to explore whether a simple and feasible application of S-ketamine before the induction of general anesthesia can prevent atelectasis. The results of this study may provide new ideas and direct clinical evidence for the prevention and treatment of perioperative pulmonary complications during anesthesia. TRIAL REGISTRATION: ClinicalTrials.gov NCT04745286. Registered on February 9, 2021.

Multifunctional polylactic acid sensing fabric based on biomass flame retardants for intelligent fire early-warning.

Today, building materials emit many hazardous gases in the event of a fire, causing great harm to human health and the environment. Therefore, it is of great significance to develop bio-based flame retardant materials and to realize preventive measures to reduce fires or their damage. In this work, we fabricated a novel multifunctional fire early-warning polylactic acid-based fabric (MFR-PBF) by coating MXene nanosheet, phytic acid @ furfurylamine (PA@FA) and ammonium polyphosphate (APP) via an eco-friendly layer-by-layer assembly method. MFR-PBF showed outstanding flame retardancy including a limiting oxygen index value of 35 % and better char formation capacity. More importantly, MFR-PBF exhibited sensitive fire early-warning capability (∼1 s) and excellent cyclic alarm stability (>15 cycles) due to the excellent semiconductor responsiveness (light and heat) and the significant catalytic char formation effect. Moreover, MFR-PBF is comfortable, flexible and strong enough to sew onto firefighter uniform to detect a variety of human motions, which can be monitored in the internet by using a LoRa emitter and a gateway. In addition, the controllable heating performance rendered MFR-PBF as a potential portable heater. This work provides new insights into the preparation and application of intelligent fire early-warning fabrics in the smart fire protection and Internet of Things.

Electrolyte Additives for Stable Zn Anodes.

Zn-ion batteries are regarded as the most promising batteries for next-generation, large-scale energy storage because of their low cost, high safety, and eco-friendly nature. The use of aqueous electrolytes results in poor reversibility and leads to many challenges related to the Zn anode. Electrolyte additives can effectively address many such challenges, including dendrite growth and corrosion. This review provides a comprehensive introduction to the major challenges in and current strategies used for Zn anode protection. In particular, an in-depth and fundamental understanding is provided of the various functions of electrolyte additives, including electrostatic shielding, adsorption, in situ solid electrolyte interphase formation, enhancing water stability, and surface texture regulation. Potential future research directions for electrolyte additives used in aqueous Zn-ion batteries are also discussed.

Safety and efficacy of doravirine as first-line therapy in adults with HIV-1: week 192 results from the open-label extensions of the DRIVE-FORWARD and DRIVE-AHEAD phase 3 trials.

BACKGROUND: In two phase 3 trials for first-line therapy in adults with HIV-1, doravirine showed non-inferior efficacy, a favourable safety profile, and a superior lipid profile to darunavir and efavirenz through to 48 and 96 weeks. Here we report 192-week results from both studies. METHODS: DRIVE-FORWARD and DRIVE-AHEAD are multicentre, double-blind, randomised, active comparator-controlled, phase 3 trials of first-line antiretroviral treatment in adults with HIV-1. Eligible participants (aged ≥18 years) were naive to antiretroviral therapy, had plasma HIV-1 RNA 1000 copies per mL or more at screening, had no known resistance to any of the trial drugs, and had creatinine clearance 50 mL per min or more. DRIVE-FORWARD was conducted at 125 sites in 15 countries and compared doravirine (100 mg) with ritonavir-boosted darunavir (ritonavir [100 mg] and darunavir [800 mg]), each administered orally once daily with two nucleoside or nucleotide reverse transcriptase inhibitors (tenofovir disoproxil fumarate [300 mg] and emtricitabine [200 mg] or abacavir sulfate [600 mg] and lamivudine [300 mg]). DRIVE-AHEAD was conducted at 126 sites in 23 countries and compared doravirine (100 mg), lamivudine (300 mg), and tenofovir disoproxil fumarate (300 mg) with that of efavirenz (600 mg), emtricitabine (200 mg), and tenofovir disoproxil fumarate (300 mg), all administered orally once daily. DRIVE-FORWARD enrolment was between Dec 1, 2014, and June 1, 2020, and DRIVE-AHEAD enrolment was between June 10, 2015, and Aug 10, 2020. After the 96-week double-blind phase, eligible participants could enter an open-label extension and either continue doravirine or switch from comparator to doravirine for an additional 96 weeks. Efficacy (HIV-1 RNA <50 copies per mL) and safety assessments (adverse events and changes in laboratory parameters) were pooled. The DRIVE-FORWARD and DRIVE-AHEAD trials were registered with ClinicalTrials.gov, NCT02275780 and NCT02403674. FINDINGS: Of 1494 participants treated in the double-blind phase (1261 [84%] male and 233 [16%] female), 550 continued doravirine and 502 switched to doravirine in the extension. Using the FDA snapshot approach, HIV-1 RNA less than 50 copies per mL was maintained in 457 (83%) of 550 participants who continued doravirine and 404 (80%) of 502 participants who switched to doravirine. Protocol-defined virological failure and development of resistance were low, occurring mainly before week 96. Two (<1%) of 550 participants who continued doravirine reported serious drug-related adverse events, and three (1%) who continued doravirine and one (<1%) of 502 who switched to doravirine discontinued due to drug-related adverse events. Participants continuing or switching to doravirine showed generally favourable lipid profiles, little weight gain, and small decreases in estimated glomerular filtration rates, with no discontinuations due to increased creatinine or renal adverse events. INTERPRETATION: Favourable efficacy and safety profiles for doravirine at week 96 were maintained through to week 192 in participants who continued or switched to doravirine, supporting use of doravirine for long-term first-line HIV-1 treatment and for virologically suppressed adults switching therapy. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.

Robust Sparse Bayesian Two-Dimensional Direction-of-Arrival Estimation with Gain-Phase Errors.

To reduce the influence of gain-phase errors and improve the performance of direction-of-arrival (DOA) estimation, a robust sparse Bayesian two-dimensional (2D) DOA estimation method with gain-phase errors is proposed for L-shaped sensor arrays. The proposed method introduces an auxiliary angle to transform the 2D DOA estimation problem into two 1D angle estimation problems. A sparse representation model with gain-phase errors is constructed using the diagonal element vector of the cross-correlation covariance matrix of two submatrices of the L-shaped sensor array. The expectation maximization algorithm derives unknown parameter expression, which is used for iterative operations to obtain off-grid and signal precision. Using these parameters, a new spatial spectral function is constructed to estimate the auxiliary angle. The obtained auxiliary angle is substituted into a sparse representation model with gain and phase errors, and then the sparse Bayesian learning method is used to estimate the elevation angle of the incident signal. Finally, according to the relationship of the three angles, the azimuth angle can be estimated. The simulation results show that the proposed method can effectively realize the automatic matching of the azimuth and elevation angles of the incident signal, and improves the accuracy of DOA estimation and angular resolution.