Structural Brain Connectivity Guided Optimal Contact Selection for Deep Brain Stimulation of the Subthalamic Nucleus.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapy in ameliorating the motor symptoms of Parkinson disease. However, postoperative optimal contact selection is crucial for achieving the best outcome of deep brain stimulation of the subthalamic nucleus surgery, but the process is currently a trial-and-error and time-consuming procedure that relies heavily on surgeons' clinical experience. METHODS: In this study, we propose a structural brain connectivity guided optimal contact selection method for deep brain stimulation of the subthalamic nucleus. Firstly, we reconstruct the DBS electrode location and estimate the stimulation range using volume of tissue activated from each DBS contact. Then, we extract the structural connectivity features by concatenating fractional anisotropy and the number of streamlines features of activated regions and the whole brain regions. Finally, we use a convolutional neural network with convolutional block attention module to identify the structural connectivity features for the optimal contact selection. RESULTS: We review the data of 800 contacts from 100 patients with Parkinson disease for the experiment. The proposed method achieves promising results, with the average accuracy of 97.63%, average precision of 94.50%, average recall of 94.46%, and average specificity of 98.18%, respectively. Our method can provide the suggestion for optimal contact selection. CONCLUSIONS: Our proposed method can improve the efficiency and accuracy of DBS optimal contact selection, reduce the dependence on surgeons' experience, and has the potential to facilitate the development of advanced DBS technology.

Intercropping with maize and sorghum-induced saikosaponin accumulation in Bupleurum chinense DC. by liquid chromatography-mass spectrometry-based metabolomics.

Bupleuri Radix is an important medicinal plant, which has been used in China and other Asian countries for thousands of years. Cultivated Bupleurum chinense DC. (B. chinense) is the main commodity of Bupleuri Radix. The benefits of intercropping with various crops for B. chinense have been recognized; however, the influence of intercropping on the chemical composition of B. chinense is still unclear yet. In this study, intercropping with sorghum and maize exhibited little effect on the root length, root diameter, and single root mass of B. chinense. Only the intercropping with sorghum increased the root length of B. chinense slightly compared to the monocropping. In addition, 200 compounds were identified by UHPLC-Q-TOF-MS, and metabolomic combined with the Venn diagram and heatmap analysis showed apparent separation between the intercropped and monocropped B. chinense samples. Intercropping with sorghum and maize could both increase the saikosaponins, fatty acyls, and organic acids in B. chinense while decreasing the phospholipids. The influence of intercropping on the saikosaponin biosynthesis was probably related with the light intensity and hormone levels in B. chinense. Moreover, we found intercropping increased the anti-inflammatory activity of B. chinense. This study provides a scientific reference for the beneficial effect of intercropping mode of B. chinense.

Multimodal MRI segmentation of key structures for microvascular decompression via knowledge-driven mutual distillation and topological constraints.

PURPOSE: Microvascular decompression (MVD) is a widely used neurosurgical intervention for the treatment of cranial nerves compression. Segmentation of MVD-related structures, including the brainstem, nerves, arteries, and veins, is critical for preoperative planning and intraoperative decision-making. Automatically segmenting structures related to MVD is still challenging for current methods due to the limited information from a single modality and the complex topology of vessels and nerves. METHODS: Considering that it is hard to distinguish MVD-related structures, especially for nerve and vessels with similar topology, we design a multimodal segmentation network with a shared encoder-dual decoder structure and propose a clinical knowledge-driven distillation scheme, allowing reliable knowledge transferred from each decoder to the other. Besides, we introduce a class-wise contrastive module to learn the discriminative representations by maximizing the distance among classes across modalities. Then, a projected topological loss based on persistent homology is proposed to constrain topological continuity. RESULTS: We evaluate the performance of our method on in-house dataset consisting of 100 paired HR-T2WI and 3D TOF-MRA volumes. Experiments indicate that our model outperforms the SOTA in DSC by 1.9% for artery, 3.3% for vein and 0.5% for nerve. Visualization results show our method attains improved continuity and less breakage, which is also consistent with intraoperative images. CONCLUSION: Our method can comprehensively extract the distinct features from multimodal data to segment the MVD-related key structures and preserve the topological continuity, allowing surgeons precisely perceiving the patient-specific target anatomy and substantially reducing the workload of surgeons in the preoperative planning stage. Our resources will be publicly available at https://github.com/JaronTu/Multimodal_MVD_Seg .

Amber rainbow ribbon effect in broadband optical metamaterials.

Using the trapped rainbow effect to slow down or even stop light has been widely studied. However, high loss and energy leakage severely limited the development of rainbow devices. Here, we observed the negative Goos-Hänchen effect in film samples across the entire visible spectrum. We also discovered an amber rainbow ribbon and an optical black hole due to perfect back reflection in optical waveguides, where little light leaks out. Not only does the amber rainbow ribbon effect show an automatic frequency selection response, as predicted by single frequency theoretical models and confirmed by experiments, it also shows spatial periodic regulation, resulting from broadband omnidirectional visible metamaterials prepared by disordered assembly systems. This broadband light trapping system could play a crucial role in the fields of optical storage and information processing when being used to construct ultra-compact modulators and other tunable devices.

Inhibition of SFTSV replication in humanized mice by a subcutaneously administered anti-PD1 nanobody.

Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening disease caused by a novel bunyavirus (SFTSV), mainly transmitted by ticks. With no effective therapies or vaccines available, understanding the disease's mechanisms is crucial. Recent studies found increased expression of programmed cell death-1 (PD-1) on dysfunctional T cells in SFTS patients. However, the role of the PD-1/programmed cell death-ligand 1 (PD-L1) pathway in SFTS progression remains unclear. We investigated PD-1 blockade as a potential therapeutic strategy against SFTSV replication. Our study analyzed clinical samples and performed in vitro experiments, revealing elevated PD-1/PD-L1 expression in various immune cells following SFTSV infection. An anti-PD-1 nanobody, NbP45, effectively inhibited SFTSV infection in peripheral blood mononuclear cells (PBMCs), potentially achieved through the mitigation of apoptosis and the augmentation of T lymphocyte proliferation. Intriguingly, subcutaneous administration of NbP45 showed superior efficacy compared to a licensed anti-PD-1 antibody in an SFTSV-infected humanized mouse model. These findings highlight the involvement of the PD-1/PD-L1 pathway during acute SFTSV infection and suggest its potential as a host target for immunotherapy interventions against SFTSV infection.

6PPD-quinone exposure induces neuronal mitochondrial dysfunction to exacerbate Lewy neurites formation induced by α-synuclein preformed fibrils seeding.

The emerging toxicant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) is of wide concern due to its ubiquitous occurrence and high toxicity. Despite regular human exposure, limited evidence exists about its presence in the body and potential health risks. Herein, we analyzed cerebrospinal fluid (CSF) samples from Parkinson's disease (PD) patients and controls. The CSF levels of 6PPD-Q were twice as high in PD patients compared to controls. Immunostaining assays performed with primary dopaminergic neurons confirm that 6PPD-Q at environmentally relevant concentrations can exacerbate the formation of Lewy neurites induced by α-synuclein preformed fibrils (α-syn PFF). Assessment of cellular respiration reveals a considerable decrease in neuronal spare respiratory and ATP-linked respiration, potentially due to changes in mitochondrial membrane potential. Moreover, 6PPD-Q-induced mitochondrial impairment correlates with an upsurge in mitochondrial reactive oxygen species (mROS), and Mito-TEMPO-driven scavenging of mROS can lessen the amount of pathologic phospho-serine 129 α-synuclein. Untargeted metabolomics provides supporting evidence for the connection between 6PPD-Q exposure and changes in neuronal metabolite profiles. In-depth targeted metabolomics further unveils an overall reduction in glycolysis metabolite pool and fluctuations in the quantity of TCA cycle intermediates. Given its potentially harmful attributes, the presence of 6PPD-Q in human brain could potentially be a risk factor for PD.

Ferri-hydrite: A Novel Electron-Selective Contact Layer for InP Photovoltaic and Photoelectrochemical Cells.

Solar energy conversion devices with charge-selective contacts are attracting significant research interest as a cost-effective alternative to homojunction counterparts. This study presents a novel approach for fabricating high-performance solar cells based on InP heterojunctions using a solution-processed ferri-hydrite (Fh) electron-selective contact (ESC). The champion cell efficiency of 16.6% is achieved, which is a significant improvement over those from previous studies using other solution-processed ESC materials. X-ray photoelectron spectroscopy measurements showed that the low conduction band offset at the Fh-InP interface facilitated selective transport of photogenerated electrons from InP. Moreover, the Fh electron-selective contact layer provided an excellent photoelectrochemical half-cell water reduction efficiency of 8.4%. The Fh layer not only selectively extracts photogenerated electrons from InP but also simultaneously serves as a surface protection layer, improving the cell's long-term stability. These results demonstrate the potential of Fh as a low-cost and easily fabricated material for use in high-efficiency photovoltaic and photoelectrochemical devices. Our findings pave the way for further improvements in the efficiency of InP heterojunction solar cells by addressing the losses incurred in the cells.

Automatic segmentation of white matter hyperintensities and correlation analysis for cerebral small vessel disease.

Objective: Cerebral white matter hyperintensity can lead to cerebral small vessel disease, MRI images in the brain are used to assess the degree of pathological changes in white matter regions. In this paper, we propose a framework for automatic 3D segmentation of brain white matter hyperintensity based on MRI images to address the problems of low accuracy and segmentation inhomogeneity in 3D segmentation. We explored correlation analyses of cognitive assessment parameters and multiple comparison analyses to investigate differences in brain white matter hyperintensity volume among three cognitive states, Dementia, MCI and NCI. The study explored the correlation between cognitive assessment coefficients and brain white matter hyperintensity volume. Methods: This paper proposes an automatic 3D segmentation framework for white matter hyperintensity using a deep multi-mapping encoder-decoder structure. The method introduces a 3D residual mapping structure for the encoder and decoder. Multi-layer Cross-connected Residual Mapping Module (MCRCM) is proposed in the encoding stage to enhance the expressiveness of model and perception of detailed features. Spatial Attention Weighted Enhanced Supervision Module (SAWESM) is proposed in the decoding stage to adjust the supervision strategy through a spatial attention weighting mechanism. This helps guide the decoder to perform feature reconstruction and detail recovery more effectively. Result: Experimental data was obtained from a privately owned independent brain white matter dataset. The results of the automatic 3D segmentation framework showed a higher segmentation accuracy compared to nnunet and nnunet-resnet, with a p-value of <0.001 for the two cognitive assessment parameters MMSE and MoCA. This indicates that larger brain white matter are associated with lower scores of MMSE and MoCA, which in turn indicates poorer cognitive function. The order of volume size of white matter hyperintensity in the three groups of cognitive states is dementia, MCI and NCI, respectively. Conclusion: The paper proposes an automatic 3D segmentation framework for brain white matter that achieves high-precision segmentation. The experimental results show that larger volumes of segmented regions have a negative correlation with lower scoring coefficients of MMSE and MoCA. This correlation analysis provides promising treatment prospects for the treatment of cerebral small vessel diseases in the brain through 3D segmentation analysis of brain white matter. The differences in the volume of white matter hyperintensity regions in subjects with three different cognitive states can help to better understand the mechanism of cognitive decline in clinical research.

Exosomal circ_0008285 in follicle fluid regulates the lipid metabolism through the miR-4644/ LDLR axis in polycystic ovary syndrome.

PURPOSE: Exosomal circRNA, as an essential mediator of the follicular microenvironment, has been implicated in the etiological and pathobiological studies of polycystic ovarian syndrome (PCOS). This study aimed to determine abnormal circular RNA (circRNA) expression profiles in follicle fluid (FF) exosomes in patients with PCOS and identify the role of circ_0008285/microRNA (miR)-4644/low-density lipoprotein receptor (LDLR) axis in PCOS. METHODS: Sixty-seven women undergoing IVF/ICSI, 31 PCOS patients and 36 non-PCOS patients were included in the cohort study. The circRNA expression profiles of FF exosomes in PCOS (n = 3) and control group (n = 3) were compared by RNA sequencing. In an additional cohort (PCOS:28 vs Control:33), the mRNA expression levels of four circRNAs from FF exosomes were further verified by qRT-PCR. Bioinformatic analysis and dual luciferase reporter gene assay verified the relationship between circ_0008285 and miR-4644 and between miR-4644 and LDLR. KGN cells were infected with sh-circ0008285 and transfected with miR-4644 mimic to verify their roles in lipid metabolism. RESULTS: Four circRNAs showed significantly different expressions. Circ_0044234 was overexpressed in PCOS patients, while circ_0006877, circ_0013167 and circ0008285 were decreased in PCOS. Among four differentially expressed circRNAs, circ0008285 was enriched in lipoprotein particle receptor activity and cholesterol metabolism pathway by GO and KEGG pathway analyses. Luciferase assay confirmed the competing endogenous RNA (ceRNA) network circ_0008285/miR-4644 /LDLR. The intercellular experiments on circ_0008285 and its reduction in KGN cells showed that the consumption of circ_0008285 in exosomes could increase the expression of miR-4644 in recipient cells and inhibit the expression of LDLR, as well as increase free fatty acid secretion. CONCLUSION: Circ_0008285 can combine with miR-4644 to promote the expression of LDLR and affect the cholesterol metabolism of ovarian granulosa cells in PCOS. Our findings revealed the ceRNA network of circ_0008285 and provided a new path to investigate lipid metabolism abnormalities in PCOS.

The underlying mechanisms of cisplatin-induced nephrotoxicity and its therapeutic intervention using natural compounds.

Cisplatin is an effective chemotherapeutic drug widely used for the treatment of various solid tumors; however, its clinical use and efficacy are limited by its inherent nephrotoxicity. The pathogenesis of cisplatin-induced nephrotoxicity is complex and has not been fully elucidated. Cellular uptake and transport, DNA damage, apoptosis, oxidative stress, inflammatory response, and autophagy are involved in the development of cisplatin-induced nephrotoxicity. Currently, despite some deficiencies, hydration regimens remain the major protective measures against cisplatin-induced nephrotoxicity. Therefore, effective drugs must be explored and developed to prevent and treat cisplatin-induced kidney injury. In recent years, many natural compounds with high efficiency and low toxicity have been identified for the treatment of cisplatin-induced nephrotoxicity, including quercetin, saikosaponin D, berberine, resveratrol, and curcumin. These natural agents have multiple targets, multiple effects, and low drug resistance; therefore, they can be safely used as a supplementary regimen or combination therapy for cisplatin-induced nephrotoxicity. This review aimed to comprehensively describe the molecular mechanisms underlying cisplatin-induced nephrotoxicity and summarize natural kidney-protecting compounds to provide new ideas for the development of better therapeutic agents.

Treatment of hemimasticatory spasm secondary to parry-romberg syndrome via partial resection of the trigeminal nerve motor branch under intraoperative neurophysiological monitoring: A case report and literature review.

Parry-Romberg syndrome (PRS) combined with hemimasticatory spasm (HMS) is a rare craniofacial disorder characterized by unilateral facial tissue atrophy with paroxysmal involuntary contractions of the jaw-closing muscles. Although a majority believe that this is a result of demyelination changes from the effect of the facial involvement of PRS on the trigeminal nerve motor branches, the mechanism of PRS is presently unclear. Moreover, the therapeutic effects of existing drugs that target PRS have not been satisfactory. For intolerable spasms of the masticatory muscles, botulinum toxin injection may temporarily relieve the symptoms of spasms. We report a case of HMS secondary to PRS that was treated via a partial resection of the trigeminal nerve motor branch under intraoperative neurophysiological monitoring.

Effect of advanced paternal age on reproductive outcomes in IVF cycles of non-male-factor infertility: a retrospective cohort study.

Advanced paternal age has been overlooked, and its effect on fertility remains controversial. Previous studies have focused mainly on intracytoplasmic sperm injection (ICSI) cycles in men with oligozoospermia. However, few studies have reported on men with semen parameters within reference ranges. Therefore, we conducted a retrospective cohort study analyzing the reproductive outcomes of couples with non-male-factor infertility undergoing in vitro fertilization (IVF) cycles. In total, 381 cycles included were subgrouped according to paternal age (<35-year-old, 35-39-year-old, or ≥40-year-old), and maternal age was limited to under 35 years. Data on embryo quality and clinical outcomes were analyzed. The results showed that fertilization and high-quality embryo rates were not significantly different (all P > 0.05). The pregnancy rate was not significantly different in the 35-39-year-old group (42.0%; P > 0.05), but was significantly lower in the ≥40-year-old group (26.1%; P < 0.05) than that in the <35-year-old group (40.3%). Similarly, the implantation rate significantly decreased in the ≥40-year-old group (18.8%) compared with that in the <35-year-old group (31.1%) and 35-39-year-old group (30.0%) (both P < 0.05). The live birth rate (30.6%, 21.7%, and 19.6%) was not significantly different across the paternal age subgroups (<35-year-old, 35-39-year-old, and ≥40-year-old, respectively; all P > 0.05), but showed a declining trend. The miscarriage rate significantly increased in the 35-39-year-old group (44.8%) compared with that in the <35-year-old group (21.0%; P < 0.05). No abnormality in newborn birth weight was found. The results indicated that paternal age over 40 years is a key risk factor that influences the assisted reproductive technology success rate even with good semen parameters, although it has no impact on embryo development.

Discovery of novel DNA-damaging agents through phenotypic screening for DNA double-strand break.

DNA double-strand breaks (DSBs) seriously damage DNA and promote genomic instability that can lead to cell death. They are the source of conditions such as carcinogenesis and aging, but also have important applications in cancer therapy. Therefore, rapid detection and quantification of DSBs in cells are necessary for identifying carcinogenic and anticancer factors. In this study, we detected DSBs using a flow cytometry-based high-throughput method to analyze γH2AX intensity. We screened a chemical library containing 9600 compounds and detected multiple DNA-damaging compounds, although we could not identify mechanisms of action through this procedure. Thus, we also profiled a representative compound with the highest DSB potential, DNA-damaging agent-1 (DDA-1), using a bioinformatics-based method we termed "molecular profiling." Prediction and verification analysis revealed DDA-1 as a potential inhibitor of topoisomerase IIα, different from known inhibitors such as etoposide and doxorubicin. Additional investigation of DDA-1 analogs and xenograft models suggested that DDA-1 is a potential anticancer drug. In conclusion, our findings established that combining high-throughput DSB detection and molecular profiling to undertake phenotypic analysis is a viable method for efficient identification of novel DNA-damaging compounds for clinical applications.

Follicular fluid steroid and gonadotropic hormone levels and mitochondrial function from exosomes predict embryonic development.

Purpose: Human follicular fluid (FF) is a complex biological fluid that contributes to the micro-environment of oocyte development. The aim of this study was to evaluate the role of steroid and gonadotropic hormones levels and mitochondrial function in embryo development during in vitro fertilization cycles. Methods: This was a cohort study of 138 women receiving IVF/ICSI, including 136 FF samples from 109 infertile women. FF steroid and gonadotropic hormones levels were tested by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and immunoassays. The mRNA expression levels of mitochondrial electron transport chain (ETC) complex genes from FF exosomes were detected by qPCR. Results: Analysis of these individual FF concentrations revealed that LH and FSH concentrations were higher in follicles in which the oocyte developed into a top quality (TQ) blastocyst (LH: 9.44 ± 2.32mIU/ml, FSH: 9.32 ± 1.01mIU/ml) than those in which there was a failure of fertilization (LH: 5.30 ± 0.84mIU/ml, FSH: 6.91 ± 0.62mIU/ml). In contrast, follicular cortisone concentrations were lower for oocytes that resulted in a TQ blastocyst (12.20 ± 0.82mIU/ml). The receiver operating characteristic analysis showed that FF LH and FSH levels predicted TQ blastocyst with excellent AUC value of 0.711 and 0.747. Mitochondrial ETC complex I and III mRNA levels were increased in the FF exosomes of TQ blastocyst. Correlation analysis showed that mRNA levels of ETC complex I was positively correlated with LH and FSH levels in FF. Conclusion: The levels of FF steroid and gonadotropic hormones from single follicle can predetermine subsequent embryo development to some extent. Furthermore, impaired exosome mitochondrial dysfunction is a potiential event that causes hormone change in embryo development.

Design, synthesis, and biological evaluation of ocotillol derivatives fused with 2-aminothiazole via A-ring as modulators of P-glycoprotein-mediated multidrug resistance.

Overexpression of P-glycoprotein (P-gp) plays a key role in the development of multidrug resistance (MDR), the major reason for the failure of chemotherapy in clinics. Ocotillol and its derivatives had been reported with good P-gp-mediated tumor MDR reversal activity in vitro. Herein, a series of ocotillol derivatives fused with 2-aminothiazole (2-AT) via A-ring were designed and synthesized to further improve the tumor MDR reversal potency. These compounds were evaluated for their MDR reversal activity against the KBV cells by MTT assay. Among them, the most promising derivative against P-gp-mediated MDR was compound 12 with 2-AT and glycine in the A-ring. Rhodamine123 (Rh123) accumulation assay, Western blot assay, and P-gp-Glo™ assay showed that compound 12 efficiently inhibited the efflux function of P-gp by stimulating P-gp ATPase rather than downregulating its expression. Moreover, compound 12 sensitized KBV cells to paclitaxel arrested cells in the G2/M phase and induced cell apoptosis. Importantly, compound 12 significantly inhibited the growth of KBV cell-derived xenograft tumors in nude mice by increasing the sensitivity of paclitaxel in vivo. Finally, the structure-activity relationships (SARs) of ocotillol derivatives were further investigated. In summary, compound 12 has the potential to overcome MDR in cancer caused by P-gp.

Mitochondrial dysfunction in cumulus cells is related to decreased reproductive capacity in advanced-age women.

OBJECTIVE: To reveal the relationship between mitochondrial function in cumulus cells (CCs) and the aging-related decline in ovarian function and reproductive capacity. DESIGN: Retrospective and transcriptome analysis of human tissue. SETTING: University hospital. PATIENT(S): A total of 186 infertile women with normal weight and no other diseases, including 86 young women (aged <38 years) with normal ovarian reserve and 100 advanced-age women (aged ≥38 years) with diminished ovarian reserve. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Embryo development data were analyzed. The mitochondrial ultrastructure of CCs was observed by transmission electron microscopy. Mitochondrial activity was detected by immunofluorescence. The per-CC mitochondrial deoxyribonucleic acid copy numbers and cellular adenosine triphosphate levels were quantified. Unbiased comprehensive genome-wide transcriptomics was performed. The functions of all annotated genes and biologic pathways were analyzed by the Kyoto Encyclopedia of Genes and Genomes. RESULT(S): Advanced-age women with diminished ovarian function had significantly fewer retrieved oocytes and lower embryo quality. The normal mitochondrial rate in CCs was significantly lower. In addition to mitochondrial morphology and structural changes, the fluorescence intensity of Fluo-3/AM was significantly higher, and that of MitoTracker was lower than that of young women with normal ovarian reserve, suggesting that age negatively affects the mitochondrial activity of CCs. The per-CC mitochondrial deoxyribonucleic acid copy number and adenosine triphosphate levels significantly decreased in the advanced-age group. The Kyoto Encyclopedia of Genes and Genomes analysis showed that differentially expressed genes were significantly enriched in the oxidative phosphorylation pathway. Additionally, most mitochondrially encoded genes related to oxidative phosphorylation were significantly down-regulated in the advanced-age group. CONCLUSION(S): We present current evidence that mitochondrial dysfunction in CCs may play a key role in the age-related decline in ovarian function and reproductive capacity.

Engineering a Kesterite-Based Photocathode for Photoelectrochemical Ammonia Synthesis from NOx Reduction.

Ammonia is a key chemical feedstock for industry as well as future carbon-free fuel and transportable vector for renewable energy. Photoelectrochemical (PEC) ammonia synthesis from NOx reduction reaction (NOx RR) provides not only a promising alternative to the energy-intensive Haber-Bosch process through direct solar-to-ammonia conversion, but a sustainable solution for balancing the global nitrogen cycle by restoring ammonia from wastewater. In this work, selective ammonia synthesis from PEC NOx RR by a kesterite (Cu2 ZnSnS4 [CZTS]) photocathode through loading defect-engineered TiOx cocatalyst on a CdS/CZTS photocathode (TiOx /CdS/CZTS) is demonstrated. The uniquely designed photocathode enables selective ammonia production from NOx RR, yielding up to 89.1% Faradaic efficiency (FE) (0.1 V vs reversible hydrogen electrode (RHE)) with a remarkable positive onset potential (0.38 V vs RHE). By tailoring the amount of surface defective Ti3+ species, the adsorption of reactant NO3 - and * NO2  intermediate is significantly promoted while the full coverage of TiOx also suppresses NO2 - liberation as a by-product, contributing to high ammonia selectivity. Further attempts on PEC ammonia synthesis from simulated wastewater show good FE of 64.9%, unveiling the potential of using the kesterite-based photocathode for sustainably restoring ammonia from nitrate-rich wastewater.

Short-Term Instantaneous Prophylaxis and Efficient Treatment Against SARS-CoV-2 in hACE2 Mice Conferred by an Intranasal Nanobody (Nb22).

Current COVID-19 vaccines need to take at least one month to complete inoculation and then become effective. Around 51% of the global population is still not fully vaccinated. Instantaneous protection is an unmet need among those who are not fully vaccinated. In addition, breakthrough infections caused by SARS-CoV-2 are widely reported. All these highlight the unmet needing for short-term instantaneous prophylaxis (STIP) in the communities where SARS-CoV-2 is circulating. Previously, we reported nanobodies isolated from an alpaca immunized with the spike protein, exhibiting ultrahigh potency against SARS-CoV-2 and its variants. Herein, we found that Nb22, among our previously reported nanobodies, exhibited ultrapotent neutralization against Delta variant with an IC50 value of 0.41 ng/ml (5.13 pM). Furthermore, the crystal structural analysis revealed that the binding of Nb22 to WH01 and Delta RBDs both effectively blocked the binding of RBD to hACE2. Additionally, intranasal Nb22 exhibited protection against SARS-CoV-2 Delta variant in the post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP). Of note, intranasal Nb22 also demonstrated high efficacy against SARS-CoV-2 Delta variant in STIP for seven days administered by single dose and exhibited long-lasting retention in the respiratory system for at least one month administered by four doses, providing a strategy of instantaneous short-term prophylaxis against SARS-CoV-2. Thus, ultrahigh potency, long-lasting retention in the respiratory system and stability at room-temperature make the intranasal or inhaled Nb22 to be a potential therapeutic or STIP agent against SARS-CoV-2.

Bioactivities and Structure-Activity Relationships of Fusidic Acid Derivatives: A Review.

Fusidic acid (FA) is a natural tetracyclic triterpene isolated from fungi, which is clinically used for systemic and local staphylococcal infections, including methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci infections. FA and its derivatives have been shown to possess a wide range of pharmacological activities, including antibacterial, antimalarial, antituberculosis, anticancer, tumor multidrug resistance reversal, anti-inflammation, antifungal, and antiviral activity in vivo and in vitro. The semisynthesis, structural modification and biological activities of FA derivatives have been extensively studied in recent years. This review summarized the biological activities and structure-activity relationship (SAR) of FA in the last two decades. This summary can prove useful information for drug exploration of FA derivatives.