Variation in structural motifs within SARS-related coronavirus spike proteins.

SARS-CoV-2 is the third known coronavirus (CoV) that has crossed the animal-human barrier in the last two decades. However, little structural information exists related to the close genetic species within the SARS-related coronaviruses. Here, we present three novel SARS-related CoV spike protein structures solved by single particle cryo-electron microscopy analysis derived from bat (bat SL-CoV WIV1) and civet (cCoV-SZ3, cCoV-007) hosts. We report complex glycan trees that decorate the glycoproteins and density for water molecules which facilitated modeling of the water molecule coordination networks within structurally important regions. We note structural conservation of the fatty acid binding pocket and presence of a linoleic acid molecule which are associated with stabilization of the receptor binding domains in the "down" conformation. Additionally, the N-terminal biliverdin binding pocket is occupied by a density in all the structures. Finally, we analyzed structural differences in a loop of the receptor binding motif between coronaviruses known to infect humans and the animal coronaviruses described in this study, which regulate binding to the human angiotensin converting enzyme 2 receptor. This study offers a structural framework to evaluate the close relatives of SARS-CoV-2, the ability to inform pandemic prevention, and aid in the development of pan-neutralizing treatments.

ATAD1 inhibits hepatitis C virus infection by removing the viral TA-protein NS5B from mitochondria.

ATPase family AAA domain-containing protein 1 (ATAD1) maintains mitochondrial homeostasis by removing mislocalized tail-anchored (TA) proteins from the mitochondrial outer membrane (MOM). Hepatitis C virus (HCV) infection induces mitochondrial fragmentation, and viral NS5B protein is a TA protein. Here, we investigate whether ATAD1 plays a role in regulating HCV infection. We find that HCV infection has no effect on ATAD1 expression, but knockout of ATAD1 significantly enhances HCV infection; this enhancement is suppressed by ATAD1 complementation. NS5B partially localizes to mitochondria, dependent on its transmembrane domain (TMD), and induces mitochondrial fragmentation, which is further enhanced by ATAD1 knockout. ATAD1 interacts with NS5B, dependent on its three internal domains (TMD, pore-loop 1, and pore-loop 2), and induces the proteasomal degradation of NS5B. In addition, we provide evidence that ATAD1 augments the antiviral function of MAVS upon HCV infection. Taken together, we show that the mitochondrial quality control exerted by ATAD1 can be extended to a novel antiviral function through the extraction of the viral TA-protein NS5B from the mitochondrial outer membrane.

Correction: Runx1 is a central regulator of osteogenesis for bone homeostasis by orchestrating BMP and WNT signaling pathways.

[This corrects the article DOI: 10.1371/journal.pgen.1009233.].

IFT80 negatively regulates osteoclast differentiation via association with Cbl-b to disrupt TRAF6 stabilization and activation.

Excess bone loss due to increased osteoclastogenesis is a significant clinical problem. Intraflagellar transport (IFT) proteins have been reported to regulate cell growth and differentiation. The role of IFT80, an IFT complex B protein, in osteoclasts (OCs) is completely unknown. Here, we demonstrate that deletion of IFT80 in the myeloid lineage led to increased OC formation and activity accompanied by severe bone loss in mice. IFT80 regulated OC formation by associating with Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b) to promote protein stabilization and proteasomal degradation of tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6). IFT80 knockdown resulted in increased ubiquitination of Cbl-b and higher TRAF6 levels, thereby hyperactivating the receptor activator of nuclear factor-κß (NF-κß) ligand (RANKL) signaling axis and increased OC formation. Ectopic overexpression of IFT80 rescued osteolysis in a calvarial model of bone loss. We have thus identified a negative function of IFT80 in OCs.

UBR2 targets myosin heavy chain IIb and IIx for degradation: Molecular mechanism essential for cancer-induced muscle wasting.

Cancer cachexia is a lethal metabolic syndrome featuring muscle wasting with preferential loss of fast-twitching muscle mass through an undefined mechanism. Here, we show that cancer induces muscle wasting by selectively degrading myosin heavy chain (MHC) subtypes IIb and IIx through E3 ligase UBR2-mediated ubiquitylation. Induction of MHC loss and atrophy in C2C12 myotubes and mouse tibialis anterior (TA) by murine cancer cells required UBR2 up-regulation by cancer. Genetic gain or loss of UBR2 function inversely altered MHC level and muscle mass in TA of tumor-free mice. UBR2 selectively interacted with and ubiquitylated MHC-IIb and MHC-IIx through its substrate recognition and catalytic domain, respectively, in C2C12 myotubes. Elevation of UBR2 in muscle of tumor-bearing or free mice caused loss of MHC-IIb and MHC-IIx but not MHC-I and MHC-IIa or other myofibrillar proteins, including α-actin, troponin, tropomyosin, and tropomodulin. Muscle-specific knockout of UBR2 spared KPC tumor-bearing mice from losing MHC-IIb and MHC-IIx, fast-twitching muscle mass, cross-sectional area, and contractile force. The rectus abdominis (RA) muscle of patients with cachexia-prone cancers displayed a selective reduction of MHC-IIx in correlation with higher UBR2 levels. These data suggest that UBR2 is a regulator of MHC-IIb/IIx essential for cancer-induced muscle wasting, and that therapeutic interventions can be designed by blocking UBR2 up-regulation by cancer.

Autophagy induced by taurolidine protects against polymicrobial sepsis by promoting both host resistance and disease tolerance.

Sepsis, septic shock, and their sequelae are the leading causes of death in intensive care units, with limited therapeutic options. Disease resistance and tolerance are two evolutionarily conserved yet distinct defense strategies that protect the host against microbial infection. Here, we report that taurolidine administered at 6 h before septic challenge led to strong protection against polymicrobial sepsis by promoting both host resistance and disease tolerance characterized by accelerated bacterial clearance, ameliorated organ damage, and diminished vascular and gut permeability. Notably, taurolidine administered at 6 h after septic challenge also rescued mice from sepsis-associated lethality by enhancing disease tolerance to tissue and organ injury. Importantly, this in vivo protection afforded by taurolidine depends on an intact autophagy pathway, as taurolidine protected wild-type mice but was unable to rescue autophagy-deficient mice from microbial sepsis. In vitro, taurolidine induced light chain 3-associated phagocytosis in innate phagocytes and autophagy in vascular endothelium and gut epithelium, resulting in augmented bactericidal activity and enhanced cellular tolerance to endotoxin-induced damage in these cells. These results illustrate that taurolidine-induced autophagy augments both host resistance and disease tolerance to bacterial infection, thereby conferring protection against microbial sepsis.

Chemical Bath Deposited Antimony Oxide Thin Films for Efficient Perovskite Solar Cells.

The metal oxide electron transport layers (ETLs) of n-i-p perovskite solar cells (PSCs) are dominated by TiO2 and SnO2, while the efficacy of the other metal oxide ETLs still lags far behind. Herein, an emerging, economical, and environmentally friendly metal oxide, antimony oxide (Sb2Ox, x = 2.17), prepared by chemical bath deposition is reported as an alternative ETL for PSCs. The deposited Sb2Ox film is amorphous and very thin (∼10 nm) but conformal on rough fluorine-doped tin oxide substrates, showing matched energy levels, efficient electron extraction, and then reduced nonradiative recombination in PSCs. The champion PSC based on the Sb2Ox ETL delivers an impressive power conversion efficiency of 24.7% under one sun illumination, which represents the state-of-the-art performance of all metal oxide ETL-based PSCs. Additionally, the Sb2Ox-based devices show improved operational and thermal stability compared to their SnO2-based counterparts. Armed with these findings, we believe this work offers an optional ETL for perovskites-based optoelectronic devices.

Incidence and Outcomes of Posterior Circulation Involvement in Moyamoya Disease.

BACKGROUND: Moyamoya disease (MMD) is a progressive, occlusive disease of the internal carotid arteries and their proximal branches, with the subsequent development of an abnormal vascular network that is rupture-prone. Steno-occlusive changes in the posterior cerebral arteries (PCAs) may contribute to worsened outcomes in patients with MMD; however, there is little information on the incidence and natural history of posterior circulation MMD (PCMMD). We describe clinical PCMMD characteristics in a large cohort of patients with MMD. METHODS: We retrospectively reviewed patients with MMD treated between 1991 and 2019 at a large academic medical center. Demographics, perioperative outcomes, and radiological phenotypes were recorded for 770 patients. PCA disease was graded as either 0 (no disease), 1 (mild), 2 (moderate), or 3 (severe or occluded) based on cerebral angiography. Patients with angiographically confirmed MMD diagnosis with at least 6 months follow-up and completion of revascularization surgery were included; patients with intracranial atherosclerosis, intracranial dissection, vasculitis, and undefined inflammatory processes were excluded. The presence of stenosis/occlusion was graded radiographically to assess for disease progression and the prevalence of risk factors related to reduced progression-free survival. RESULTS: In all, 686 patients met the inclusion criteria, with PCA disease identified in 282 (41.1%) patients. Of those 282 patients with PCMMD, disease severity ranged from 99 (35.1%) with mild, 72 (25.5%) with moderate, and 111 (39.4%) with severe. The total number of postoperative complications was significantly associated with PCMMD severity (P=0.0067). Additionally, PCMMD severity correlated with worse postoperative modified Rankin Scale scores (P<0.0001). At a mean follow-up of 6.0±3.9 (range, 0.1-25.0) years, a total of 60 (12.6%) patients showed new/worsening PCMMD. The overall postoperative, progression-free survival in patients with PCMMD was 95.4% at 1 year, 82.4% at 3 years, 68.8% at 5 years, and 28.3% at 10 years, with prognostic factors for progression including preoperative PCMMD status, history of tobacco use, and hypertension (P<0.0001, P<0.001, and P<0.0001, respectively). CONCLUSIONS: PCA disease involvement in MMD is associated with higher rates of ischemic perioperative complications and worsened functional outcomes, likely due to reduced collateral flow. Ten-year progression of PCA disease is highly likely and should be monitored throughout follow-up; future studies will assess the impact of PCA disease progression on long-term outcomes.

Development of Broad-Spectrum Nanobodies for the Therapy and Diagnosis of SARS-CoV-2 and Its Multiple Variants.

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evaded the efficacy of previously developed antibodies and vaccines, thus remaining a significant global public health threat. Therefore, it is imperative to develop additional antibodies that are capable of neutralizing emerging variants. Nanobodies, as the smallest functional single-domain antibodies, exhibit enhanced stability and penetration ability, enabling them to recognize numerous concealed epitopes that are inaccessible to conventional antibodies. Herein, we constructed an immune library based on the immunization of alpaca with the S1 subunit of the SARS-CoV-2 spike protein, from which two nanobodies, Nb1 and Nb2, were selected using phage display technology for further characterization. Both nanobodies, with the binding residues residing within the receptor-binding domain (RBD) region of the spike, exhibited high affinity toward the S1 subunit. Moreover, they displayed cross-neutralizing activity against both wild-type SARS-CoV-2 and 10 ο variants, including BA.1, BA.2, BA.3, BA.5, BA.2.75, BF.7, BQ.1, EG.5.1, XBB.1.5, and JN.1. Molecular modeling and dynamics simulations predicted that both nanobodies interacted with the viral RBD through their complementarity determining region 1 (CDR1) and CDR2. These two nanobodies are novel tools for the development of therapeutic and diagnostic countermeasures targeting SARS-CoV-2 variants and potentially emerging coronaviruses.

The role of DNA and RNA guanosine oxidation in cardiovascular diseases.

Cardiovascular diseases (CVD) persist as a prominent cause of mortality worldwide, with oxidative stress constituting a pivotal contributory element. The oxidative modification of guanosine, specifically 8-oxoguanine, has emerged as a crucial biomarker for oxidative stress, providing novel insights into the molecular underpinnings of CVD. 8-Oxoguanine can be directly generated at the DNA (8-oxo-dG) and RNA (8-oxo-G) levels, as well as at the free nucleotide level (8-oxo-dGTP or 8-oxo-GTP), which are produced and can be integrated through DNA replication or RNA transcription. When exposed to oxidative stress, guanine is more readily produced in RNA than in DNA. A burgeoning body of research surrounds 8-oxoguanine, exhibits its accumulation playing a pivotal role in the development of CVD. Therapeutic approaches targeting oxidative 8-Oxoguanine damage to DNA and RNA, encompassing the modulation of repair enzymes and the development of small molecule inhibitors, are anticipated to enhance CVD management. In conclusion, we explore the noteworthy elevation of 8-oxoguanine levels in patients with various cardiac conditions and deliberate upon the formation and regulation of 8-oxo-dG and 8-oxo-G under oxidative stress, as well as their function in CVD.

Factors that determine glucose variability, defined by the coefficient of variation in continuous glucose monitoring values, in a Chinese population with type 2 diabetes.

AIMS: To elucidate the clinical determinants of the coefficient of variation (CV) of glucose by analysing the pancreatic ß-cell function of subjects with type 2 diabetes mellitus (T2DM). METHODS: A total of 716 Chinese subjects with T2DM were included. Continuous glucose monitoring (CGM) was used to assess blood glucose, and the CV was calculated. C-peptide concentration at 0, 0.5, 1, 2 and 3 hours (Cp0h, Cp0.5h, Cp1h, Cp2h and Cp3h, respectively) was measured after a standard 100-g steamed bun meal test to assess pancreatic ß-cell function. The determinants of glucose variability defined by the CV of CGM values were explored from two perspectives: the CV of qualitative variables and the CV of quantitative variables. RESULTS: Our data revealed that C-peptide concentration (Cp0h, Cp0.5h, Cp1h, Cp2h, Cp3h), area under the curve for C-peptide concentration at 0.5 and 3 hours (AUC-Cp0.5h and AUC-Cp3h) decreased with increasing CV quartile (P < 0.05). The CV was negatively correlated with homeostatic model assessment of ß-cell function index, C-peptide concentration at all timepoints, and AUC-Cp0.5h and AUC-Cp3h (P < 0.001). Quantile regression analysis showed that AUC-Cp0.5h had an overall negative effect on the CV in the 0.05 to 0.95 quartiles, and AUC-Cp3h tended to have a negative effect on the CV in the 0.2 to 0.65 quartiles. After adjusting for confounders, multinomial logistic regression showed that each 1-unit increase in AUC-Cp0.5h was associated with a 31.7% reduction in the risk of unstable glucose homeostasis (CV > 36%; P = 0.036; odds ratio 0.683; 95% confidence interval 0.478-0.976). We also identified the AUC-Cp0.5h (0.735 ng/mL) and AUC-Cp3h (13.355 ng/mL) cut-off values for predicting unstable glucose homeostasis (CV >36%) in T2DM subjects. CONCLUSION: Our study suggests that impaired pancreatic ß-cell function may be a clinical determining factor of CV of glucose in people with T2DM.

Investigations of associations between TNF-α promoter polymorphisms and genetic susceptibility to type 2 diabetes mellitus: A cross-sectional study in Chinese Han population.

Type 2 diabetes (T2DM) is characterised by insulin resistance and a relative shortage of insulin secretion. Tumour necrosis factor-α (TNF-α) plays an important role in insulin resistance by impairing insulin signal transduction. The variants of the TNF-α promoter region are considered to influence its transcription and are associated with the TNF-α level. Therefore, it is worth detecting the association of the variants in the TNF-α gene with the development of T2DM. The aim of this study was to investigate the association of five variants (rs1799964, rs1800630, rs1799724, rs1800629 and rs361525) in the TNF-α gene promoter region with T2DM in a Chinese Han population. A total of 713 subjects with T2DM and 751 nondiabetic subjects were genotyped using the TaqMan method. The associations of the five variants with the development of T2DM were evaluated. The associations of the five variant genotypes with metabolic traits in nondiabetic subjects were analysed. Our data showed that the A allele of rs1800629 could increase the risk of developing T2DM (p = .002, OR = 1.563; 95% CI: 1.18-2.08). According to inheritance mode analysis, compared with the G/G genotype, the G/A+2A/A genotype of rs1800629 showed a risk effect on T2DM in the log-additive mode (p = .002, OR = 1.56; 95% CI: 1.17-2.07). The haplotypes analysis identified that the rs1799724-rs1800629CA was associated with high risk of the development of T2DM (p = .002, OR = 1.559, 95% CI: 1.173-2.072). Conversely, the rs1799724-rs1800629CG was a protective haplotype of T2DM (p = .001, OR = 0.732, 95% CI: 0.607-0.884). Moreover, compared with the rs1799964 (T/T+C/T) genotype, the rs1799964 C/C genotype was associated with higher glycosylated haemoglobin (HbA1c) levels in nondiabetic subjects (p = .017). Our results revealed that the rs1800629 in the TNF-α gene promoter region was associated with T2DM in a Chinese Han population.

Runx1 is a central regulator of osteogenesis for bone homeostasis by orchestrating BMP and WNT signaling pathways.

Runx1 is highly expressed in osteoblasts, however, its function in osteogenesis is unclear. We generated mesenchymal progenitor-specific (Runx1f/fTwist2-Cre) and osteoblast-specific (Runx1f/fCol1α1-Cre) conditional knockout (Runx1 CKO) mice. The mutant CKO mice with normal skeletal development displayed a severe osteoporosis phenotype at postnatal and adult stages. Runx1 CKO resulted in decreased osteogenesis and increased adipogenesis. RNA-sequencing analysis, Western blot, and qPCR validation of Runx1 CKO samples showed that Runx1 regulates BMP signaling pathway and Wnt/ß-catenin signaling pathway. ChIP assay revealed direct binding of Runx1 to the promoter regions of Bmp7, Alk3, and Atf4, and promoter mapping demonstrated that Runx1 upregulates their promoter activity through the binding regions. Bmp7 overexpression rescued Alk3, Runx2, and Atf4 expression in Runx1-deficient BMSCs. Runx2 expression was decreased while Runx1 was not changed in Alk3 deficient osteoblasts. Atf4 overexpression in Runx1-deficient BMSCs did not rescue expression of Runx1, Bmp7, and Alk3. Smad1/5/8 activity was vitally reduced in Runx1 CKO cells, indicating Runx1 positively regulates the Bmp7/Alk3/Smad1/5/8/Runx2/ATF4 signaling pathway. Notably, Runx1 overexpression in Runx2-/- osteoblasts rescued expression of Atf4, OCN, and ALP to compensate Runx2 function. Runx1 CKO mice at various osteoblast differentiation stages reduced Wnt signaling and caused high expression of C/ebpα and Pparγ and largely increased adipogenesis. Co-culture of Runx1-deficient and wild-type cells demonstrated that Runx1 regulates osteoblast-adipocyte lineage commitment both cell-autonomously and non-autonomously. Notably, Runx1 overexpression rescued bone loss in OVX-induced osteoporosis. This study focused on the role of Runx1 in different cell populations with regards to BMP and Wnt signaling pathways and in the interacting network underlying bone homeostasis as well as adipogenesis, and has provided new insight and advancement of knowledge in skeletal development. Collectively, Runx1 maintains adult bone homeostasis from bone loss though up-regulating Bmp7/Alk3/Smad1/5/8/Runx2/ATF4 and WNT/ß-Catenin signaling pathways, and targeting Runx1 potentially leads to novel therapeutics for osteoporosis.

Renal protection of HWL-088 and ZLY032, two dual GPR40/PPARδ agonists, in adenine-induced renal fibrosis model.

This research examined the potential of novel GPR40/PPARδ dual agonists, HWL-088 and ZLY-032, to protect the kidneys in a mouse model of adenine-induced renal fibrosis. Mice were given a diet containing 0.25% adenine to develop renal fibrosis and then received different dosages of HWL-088 or ZLY-032. After being euthanized, tissue and serum samples were collected for morphological, histological, and molecular examination. Compared to the control group, mice fed adenine showed an increase in kidney-to-body weight ratio, serum creatinine, and urea levels. Hematoxylin and eosin staining revealed alleviated glomerulosclerosis, tubular dilation, and inflammatory cell infiltration in mice treated with HWL-088 or ZLY-032. Furthermore, Masson staining and immunohistochemistry demonstrated that these dual agonists protected against renal interstitial fibrosis and inflammation, corroborated by decreased expression levels of fibrosis-related proteins (TGF-ß, Collα1, TIMP-1) and pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6). Accordingly, it can be inferred that GPR40/PPARδ dual agonists HWL-088 and ZLY-032 could yield significant renoprotective effects by inhibiting inflammation and fibrosis. Overall, these results may contribute to the development of novel therapeutic strategies for renal fibrosis.

In-lake water turnover time shapes the distribution pattern of phytoplankton communities in a river-connected floodplain lake.

In floodplains, phytoplankton communities are mainly shaped by environmental heterogeneity, hydrological connectivity, and habitat diversity. However, it remains unclear how hydrological connectivity drives phytoplankton biodiversity in floodplain lakes. This study was carried out in the Dongting Lake connected to the Yangtze River to ascertain the response mechanisms of phytoplankton communities to different hydrological connectivity gradients. We quantified the hydrological connectivity between lake and river habitats using in-lake water turnover time, and identified its relationship with phytoplankton community structure. Changes in hydrological connectivity can lead to different hydrodynamic and environmental conditions, which have a direct or indirect impact on phytoplankton community structure in water environments. The results showed that spatiotemporal changes in the hydrological connectivity and water environment led to distinct spatial variation in phytoplankton community structure across the study area. α and ß diversity showed a consistent change law with the change of turnover time, and the diversity index gradually increased with the decrease of hydrological connectivity, reaching the maximum value at the moderate hydrological connectivity, and then gradually decreasing. The peak of ß diversity occurs earlier than the peak of α diversity during the decline of hydrological connectivity. This study demonstrates that in-lake water turnover time has a non-negligible impact on phytoplankton community distribution in river-connected lakes. Phytoplankton can maintain the highest α diversity and possibly ß diversity under moderate hydrological connectivity, which is crucial for maintaining aquatic biodiversity in floodplain lakes.

Thermal stratification and mixing processes response to meteorological factors in a monomictic reservoir.

Formation and extinction of thermal stratifications impact the reservoir ecosystems and have been closely influenced by meteorological and hydrological factors. However, quantifying the relative importance of these crucial environmental factors and mechanisms in reservoir regions characterized by various depths remain comparatively uninvestigated. Tianbao Reservoir is a typical monomictic warm and drinking water source reservoir in Southwest China. This study supplemented field observations with a three-dimensional numerical simulation model to quantitatively analyze mixing and turnover events. Air temperature and wind were two important meteorological factors resulting in hydrodynamics during stratification and mixing processes. Air temperature led to variations in stratification strength and wind-induced fluctuations of thermocline depth. A 10% rise in air temperature increased stratification strength by 18%, and a 3 m/s rise in wind speed induced the deepening of the thermocline by 2.09 m. Two hydrodynamics involved penetrative convection caused by temperature plummets and wind-induced mixing during winter turnover events were identified. Penetrative convection was the main driving force, and wind shear mixed the upper 21% of the mixed layer, which was contributed by convection. Response of water temperature to air temperature in shallow regions was faster (58 d), and the mixing depth caused by the wind was smaller than that in deep regions. Research on physical processes during stratification and mixing processes can provide support for further study on water quality deterioration distributions.

Improvement of biotic nitrate reduction in constructed photoautotrophic biofilm-soil microbial fuel cells.

The biotic nitrate reduction rate in freshwater ecosystems is typically constrained by the scarcity of carbon sources. In this study, 'two-chambers' - 'two-electrodes' photoautotrophic biofilm-soil microbial fuel cells (P-SMFC) was developed to accelerate nitrate reduction by activating in situ electron donors that originated from the soil organic carbon (SOC). The nitrate reduction rate of P-SMFC (0.1341 d-1) improved by âˆ¼ 1.6 times on the 28th day compared to the control photoautotrophic biofilm. The relative abundance of electroactive bacterium increased in the P-SMFC and this bacterium contributed to obtain electrons from SOC. Biochar amendment decreased the resistivity of P-SMFC, increased the electron transferring efficiency, and mitigated anodic acidification, which continuously facilitated the thriving of putative electroactive bacterium and promoted current generation. The results from physiological and ecological tests revealed that the cathodic photoautotrophic biofilm produced more extracellular protein, increased the relative abundance of Lachnospiraceae, Magnetospirillaceae, Pseudomonadaceae, and Sphingomonadaceae, and improved the activity of nitrate reductase and ATPase. Correspondingly, P-SMFC in the presence of biochar achieved the highest reaction rate constant for nitrate reduction (kobs) (0.2092 d-1) which was 2.4 times higher than the control photoautotrophic biofilm. This study provided a new strategy to vitalize in situ carbon sources in paddy soil for nitrate reduction by the construction of P-SMFC.

[Application of microwave vacuum drying with process management in extract drying of personalized traditional Chinese medicine preparations].

Extracts are important intermediates in the production of traditional Chinese medicines preparations. The drying effect of extracts will directly affect the subsequent production process and the quality of the preparation. To meet the requirements of high drug loading, short time consumption, and simple production process of personalized traditional Chinese medicine preparations, this study explored the application of multi-program microwave vacuum drying process in the extract drying of personalized traditional Chinese medicine preparations. The influencing factors of microwave vacuum drying process were investigated for 5 excipients and 40 prescriptions. Taking the feasibility of drying, drying rate, drying time, and dried extract status as indicators, this study investigated the feeding requirements of microwave vacuum drying. With the dried extract status as the evaluation indicator, the three drying programs(A, B, and C) were compared to obtain the optimal drying condition. The experimental results showed that the optimal feeding conditions for microwave vacuum drying were material layer thickness of 2 cm and C program(a total of 7 drying processes), which solved the problem of easy scorching in microwave drying with process management. Furthermore, the preset moisture content of the dried extract in microwave drying should be 4%-5%, so that the dried extract of traditional Chinese medicine preparation had uniform quality, complete drying, and no scorching. This study lays a foundation for the application of microwave drying in the production of traditional Chinese medicine preparations, promoting the high-quality development of personalized traditional Chinese medicine preparations.

One-Dimensional Covalent Organic Framework-Based Multilevel Memristors for Neuromorphic Computing.

Memristors are essential components of neuromorphic systems that mimic the synaptic plasticity observed in biological neurons. In this study, a novel approach employing one-dimensional covalent organic framework (1D COF) films was explored to enhance the performance of memristors. The unique structural and electronic properties of two 1D COF films (COF-4,4'-methylenedianiline (MDA) and COF-4,4'-oxydianiline (ODA)) offer advantages for multilevel resistive switching, which is a key feature in neuromorphic computing applications. By further introducing a TiO2 layer on the COF-ODA film, a built-in electric field between the COF-TiO2 interfaces could be generated, demonstrating the feasibility of utilizing COFs as a platform for constructing memristors with tunable resistive states. The 1D nanochannels of these COF structures contributed to the efficient modulation of electrical conductance, enabling precise control over synaptic weights in neuromorphic circuits. This study also investigated the potential of these COF-based memristors to achieve energy-efficient and high-density memory devices.

High-Throughput Deposition of Recyclable SnO2 Electrodes toward Efficient Perovskite Solar Cells.

Chemical bath deposited (CBD) SnO2 is one of the most prevailing electron transport layers for realizing high-efficiency perovskite solar cells (PSCs) so far. However, the state-of-the-art CBD SnO2 process is time-consuming, contradictory to its prospect in industrialization. Herein, a simplified yet efficient method is developed for the fast deposition of SnO2 electrodes by incorporating a concentrated Sn source stabilized by the ethanol ligand with antimony (Sb) doping. The higher concentration of Sn source promotes the deposition rate, and Sb doping improves the hole-blocking capability of the CBD SnO2 layer so that its target thickness can be reduced to further save the deposition time. As a result, the deposition time can be appreciably reduced from 3-4 h to only 5 min while maintaining 95% of the maximum efficiency, indicating the power of the method toward high-throughput production of efficient PSCs. Additionally, the CBD SnO2 substrates are recyclable after removing the upper layers of complete PSCs, and the refurbished PSCs can maintain ≈98% of their initial efficiency after three recycling-and-fabrication processes.