Regulation of CD73 on NAD metabolism: Unravelling the interplay between tumour immunity and tumour metabolism.

CD73, a cell surface-bound nucleotidase, serves as a crucial metabolic and immune checkpoint. Several studies have shown that CD73 is widely expressed on immune cells and plays a critical role in immune escape, cell adhesion and migration as a costimulatory molecule for T cells and a factor in adenosine production. However, recent studies have revealed that the protumour effects of CD73 are not limited to merely inhibiting the antitumour immune response. Nicotinamide adenine dinucleotide (NAD+) is a vital bioactive molecule in organisms that plays essential regulatory roles in diverse biological processes within tumours. Accumulating evidence has demonstrated that CD73 is involved in the transport and metabolism of NAD, thereby regulating tumour biological processes to promote growth and proliferation. This review provides a holistic view of CD73-regulated NAD + metabolism as a complex network and further highlights the emerging roles of CD73 as a novel target for cancer therapies.

Magnetic multi-template molecularly imprinted polymers for selective simultaneous extraction of chlorophenols followed by determination using HPLC.

Magnetic multi-template molecularly imprinted polymers (M-mt-MIPs) were successfully synthesized by surface imprinting and multi-template imprinting strategy, using polydopamine coated magnetic multi-walled carbon nanotubes as supporting materials, five typical chlorophenols (CPs) as templates, methacrylic acid as functional monomer and ethylene glycol dimethacrylate as cross-linker. Compared to non-imprinted polymers (NIPs), the as-prepared M-mt-MIPs showed high adsorption capacity (32.58‒80.63 mg g-1), rapid mass transfer and specific selectivity for the five targeted CPs, which were applied as magnetic solid-phase extraction (MSPE) adsorbents. Parameters affecting MSPE efficiency were detailed investigated, such as adsorbents dosage, sample pH, extraction time, type and volume of desorption solvent and salt effect. Combined with HPLC-DAD, a simple, rapid and sensitive method was established, showing good linearity (2‒200 µg L-1), low limits of detection (0.32‒0.49 µg L-1), and high enrichment factors (35.2‒108). The developed M-mt-MIPs-MSPE-HPLC method was applied to enrich and determine CPs in tannery wastewater, wet-blue and crust leather, and satisfactory spiking recoveries were attained in the range of 73.95‒109.7% with relative standard deviations (RSDs) of 2.13-8.48%. This study provided a new alternative material and method to rapid simultaneously extract and analyze low concentration of typical CPs in complicated matrices.

Rationally design a novel Zn-MOF for fluorescent detection of nitrofuran antibiotics: The synthesis, structure and sensing applications.

Nitrofuran antibiotics (NFAs) residues in waterare a persistent concern for the public due to the potential threats they pose to human health and the environment. Therefore, efficient probes that are capable of detecting trace amounts of antibiotics in real water environments have become a top priority. Herein, a novel fluorescent Zn-MOF probe (MOF-1) was revealed for the highly selective and sensitive sensing of NFAs. MOF-1 was rationally constructed with Zn(NO3)2·6H2O, 5,5'-(anthracene-9,10-diyl) diisophthalic acid (H4ADIP) and 1,3-bis(imidazol-1-ylmethyl)-benzene (mbib) by using the solvothermal method. Fluorescence sensing experiments demonstrate that MOF-1 can function as a fluorescent sensor for selective, sensitive, and rapid detection of NFAs among 15 antibiotics including ciprofloxacin (CPFX), chloramphenicol (CAP), sulfonamides and NFAs. Fluorescence titration experiments indicated that MOF-1 exhibited remarkably low detection limits of 0.19 µM, 0.26 µM, and 0.34 µM for furazolidone (FZD), furaltadone (FDH) and nitrofurazone (NFZ), respectively. Meanwhile, MOF-1 was successfully employed for NFAs detection in real samples with the recoveries of 98.7 % - 104.1 %, and a relative standard deviation below 5.1 %. Moreover, the sensing mechanism could be ascribed to the synergistic effect between the internal filtering effect and photoinduced electron transfer according to the experiment results and DFT calculations. Additionally, test strips were prepared based on MOF-1 for point of care testing of NFAs.

Investigating the mechanism of Zn cross-linking of chitin in a mycelium-based leather substitute and its performance evaluation.

Mycelium-based leather substitutes with a three-dimensional reticulated structure have attracted attention owing to the negative environmental impacts of natural and synthetic leather. This study utilised Ganoderma lucidum mycelium to prepare a mycelium-based leather substitute with zinc cross-linking (MF-Zn) and evaluated its physicochemical properties and sensory performance; the conventional Cr3+ tanning method was used as reference. Results demonstrated that Zn2+ and Cr3+ formed cross-links with the -OH and -NHOCH3 groups in the polysaccharides of chitin, while Zn2+ selectively bonded to a fraction of -NH2 groups in cystine and phenylalanine. The mycelium-based leather substitute with Zn cross-linking exhibited impressive tensile strength and tear strength of 7.0 MPa and 16.4 kN/m, respectively, while demonstrating desirable organoleptic properties. The free radical-scavenging capacity of MF-Zn was assessed, revealing a DPPH radical and hydroxyl radical scavenging rates of 39.4% and 52.7%, respectively. By successfully investigating the cross-linking mechanism of mycelial fibres with Zn2+ and obtaining the stabilised mycelium-based leather substitute, this study establishes a fundamental basis for the development of sustainable leather substitutes, meeting the requirements and facilitating significant advancements in low-carbon leather substitute production.

A dual-emission fluorescent probe with independent polarity and viscosity responses: The synthesis, spectroscopy and bio-imaging applications.

Viscosity and polarity are essential parameters that play critical roles in various physiological processes. Thus, dual-emission fluorescent probes that respond to both polarity and viscosity are highly sought-after tools for studying these processes. In addressing this need, a novel fluorescent probe (L), with dual emissions centered at 460 nm and 780 nm, which can sensitively respond to polarity and viscosity respectively, has been developed. Probe (L) is constructed through rational molecular design, utilizing two conjugated synthons connected by a π-bond to form a D-π-A system. The twisted intramolecular charge transfer (TICT) state is dominant in low-viscosity environments, resulting in weak near-infrared (NIR) fluorescence. Conversely, the intramolecular charge transfer (ICT) state is expected to prevail in high-viscosity environments, leading to strong NIR fluorescence. The polarity-sensitive fluorescence centered at 460 nm can be attributed to the emission of the coumarin unit. Moreover, probe (L) exhibits low cytotoxicity and primarily targets mitochondria. By leveraging the dual-emission properties of probe (L), real-time imaging of polarity and viscosity fluctuations within cells has been achieved. Additionally, probe (L) can be used for in situ and in vivo imaging of rheumatoid arthritis (RA) with good imaging resolution.

Small Molecule Activators of Mitochondrial Fusion Prevent Congenital Heart Defects Induced by Maternal Diabetes.

Most congenital heart defect (CHD) cases are attributed to nongenetic factors; however, the mechanisms underlying nongenetic factor-induced CHDs are elusive. Maternal diabetes is one of the nongenetic factors, and this study aimed to determine whether impaired mitochondrial fusion contributes to maternal diabetes-induced CHDs and if mitochondrial fusion activators, teriflunomide and echinacoside, could reduce CHD incidence in diabetic pregnancy. We demonstrated maternal diabetes-activated FoxO3a increases miR-140 and miR-195, which in turn represses Mfn1 and Mfn2, leading to mitochondrial fusion defects and CHDs. Two mitochondrial fusion activators are effective in preventing CHDs in diabetic pregnancy.

Water bridges as the trigger in an amino functionalized Zn-MOF for highly selective and sensitive fluorescent sensing of water.

Water is a fundamental element for life. The highly selective and sensitive sensing of water is always attractive for mankind in activities such as physiological processes study and extraterrestrial life exploration. Fluorescent MOFs with precise channels and functional groups might specifically recognize water molecules with hydrogen-bond interaction or coordination effects and work as water sensors. As a proof of concept, herein, an amino functionalized Zn-MOF (named as complex 1) with pores that just right for water molecules to form hydrogen bond bridges is revealed for highly selective and sensitive fluorescent sensing of water. The single-crystal X-ray diffraction analysis indicates that the 3D framework of complex 1 is functionalized with free amino groups in the channels. Hydrogen bonds formed in the channel along b-axis as water bridges to connect two adjacent NH2bdc ligands and result in the restriction of intramolecular motions (RIM) which could responsible for the selective turn-on fluorescence response to water. Complex 1 exhibits high sensitive to trace amount of water in organic solvents and could be used for water detection in a wide range water contents. Take advantages of complex 1, portable sensors (complex 1@PMMA) were prepared and used in the highly sensitive water sensing.

Mechanically Tough and Conductive Hydrogels Based on Gelatin and Z-Gln-Gly Generated by Microbial Transglutaminase.

Gelatin-based hydrogels with excellent mechanical properties and conductivities are desirable, but their fabrication is challenging. In this work, an innovative approach for the preparation of gelatin-based conductive hydrogels is presented that improves the mechanical and conductive properties of hydrogels by integrating Z-Gln-Gly into gelatin polymers via enzymatic crosslinking. In these hydrogels (Gel-TG-ZQG), dynamic π-π stacking interactions are created by the introduction of carbobenzoxy groups, which can increase the elasticity and toughness of the hydrogel and improve the conductivity sensitivity by forming effective electronic pathways. Moreover, the mechanical properties and conductivity of the obtained hydrogel can be controlled by tuning the molar ratio of Z-Gln-Gly to the primary amino groups in gelatin. The hydrogel with the optimal mechanical properties (Gel-TG-ZQG (0.25)) exhibits a high storage modulus, compressive strength, tensile strength, and elongation at break of 7.8 MPa at 10 °C, 0.15 MPa at 80% strain, 0.343 MPa, and 218.30%, respectively. The obtained Gel-TG-ZQG (0.25) strain sensor exhibits a short response/recovery time (260.37 ms/130.02 ms) and high sensitivity (0.138 kPa-1) in small pressure ranges (0-2.3 kPa). The Gel-TG-ZQG (0.25) hydrogel-based sensors can detect full-range human activities, such as swallowing, fist clenching, knee bending and finger pressing, with high sensitivity and stability, yielding highly reproducible and repeatable sensor responses. Additionally, the Gel-TG-ZQG hydrogels are noncytotoxic. All the results demonstrate that the Gel-TG-ZQG hydrogel has potential as a biosensor for wearable devices and health-monitoring systems.

Volatile-compound fingerprinting and discrimination of positional isomers in stamp-pad ink tracing using HS-GC-IMS combined with multivariate statistical analysis.

The rising crime rate associated with document forgery has a significant impact on public safety and social stability. In document fraud cases, determining the origin of a particular stamp-pad ink is the most important objective. In this study, a comprehensive analysis of the volatile compounds in quick-drying stamp-pad inks from six commonly used brands were performed for the first time, utilizing a combination of headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) and multivariate statistical analysis methods. Visual and comparative analysis of the differential volatile components among different stamp-pad ink samples was conducted using fingerprints and volcano plots. A total of 127 volatile compounds were accurately identified, with ketones, esters, alcohols, and aldehydes being the most abundant compounds in the stamp-pad inks. Hierarchical clustering analysis (HCA), including dendrograms and clustering heatmaps, was utilized to explore the correlations between these compounds and the samples. Additionally, the precise identification of positional isomers and functional group isomers of aliphatic compounds was achieved. To achieve accurate discrimination of various stamp-pad ink samples, a multivariate statistical analysis method was utilized to establish a classification model for them. Based on the results obtained from HS-GC-IMS, effective discrimination among different brands of stamp-pad ink samples was achieved through principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). The model exhibited excellent performance, with the fit index of dependent variables (R2Y) and the predictive index of the model (Q2) values of 0.99 and 0.984, respectively. These results provided significant theoretical evidence for the application of HS-GC-IMS as an efficient technique in the analysis of volatile compounds, identification of positional isomers and functional group isomers, as well as tracing the origin of stamp-pad ink and analyzing the formation time of documents.

Rhabdomyolysis in a patient with end-stage renal disease and SARS-CoV-2 infection: A case report.

RATIONALE: Rhabdomyolysis can be an uncommon complication of coronavirus disease 2019 (COVID-19) infection. However, the diagnosis of rhabdomyolysis could be easily missed due to its atypical clinical presentations. We present a patient with a history of end-stage renal disease (ESRD) who contracted COVID-19 and subsequently developed rhabdomyolysis. We discuss and share our experience in the management of this patient. PATIENT CONCERNS: An 85-year-old male with ESRD undergoing routine hemodialysis was tested positive for COVID-19. The patient had clinical symptoms of fatigue, muscle pain, and difficulty walking. DIAGNOSIS: The serum creatine kinase (CK) level was markedly elevated to 32,492.9U/L, supporting the diagnosis of rhabdomyolysis. A computed tomography scan revealed muscle injuries throughout the body, confirming the diagnosis. INTERVENTIONS: The patient was managed through electrolyte corrections and continuous renal replacement therapy. OUTCOMES: Repeat tests showed decreased levels of serum CK and negative severe acute respiratory syndrome coronavirus 2. His clinical symptoms, including fatigue and muscle pain, had significantly improved. LESSONS: COVID-19 infection can cause muscle pain and fatigue, which can mask the symptoms of rhabdomyolysis. A missed diagnosis of rhabdomyolysis can be severe, especially in patients with ESRD. The serum CK level should be tested with clinical suspicion. Appropriate management, including adequate hydration and electrolyte balance, should be provided. Continuous renal replacement therapy should be considered in affected patients with renal insufficiency.

Amino-Functionalized Silica@Resorcinol-Formaldehyde Nanocomposites for the Removal of Cr(VI) from Aqueous Solutions.

Amino-functionalized silica@resorcinol-formaldehyde nanocomposites (NH2-SiO2@RF) were synthesized for the removal of Cr(VI) from aqueous solutions using the sol-gel technique with two simple preparation steps, including the one-pot synthesis of SiO2@RF using the Stöber method and (3-aminopropyl)triethoxysilane (APTES) modification. The morphology, particle size, functional group, and thermal stability of the obtained nanocomposites were systematically characterized, with the results indicating a uniform sphericity with a particle size of 200 nm and high thermal stability. The adsorption results demonstrated that the preferred pH value was 2, and the data were well fitted with the Langmuir and Temkin isotherm models and quasi-second-order kinetic equation, indicating a high adsorption capacity. The maximum Cr(VI) adsorption capacity from the nonlinear form of the Langmuir model was 272.6 mg·g-1. The intra-particle diffusion model accurately described the adsorption of Cr(VI) onto NH2-SiO2@RF. The changes in Gibb's free energy, enthalpy, and entropy revealed that Cr(VI) adsorption onto NH2-SiO2@RF was a spontaneous and endothermic process. Furthermore, high selectivity was demonstrated in the material for the removal of Cr(VI) from commonly coexisting ions. The obtained nanocomposites had good regeneration properties and maintained a removal rate above 85% in the fifth adsorption-desorption experiments. Moreover, under the optimized adsorption conditions, the obtained nanocomposites were preliminarily applied to tannery wastewater, demonstrating an excellent removal effect, which indicates their potential application value.

One-pot preparation of supramolecularly functionalized silver nanoparticles for surface plasmon resonance based dual-modal sensing of phytotoxic polychlorinated biphenyl.

Polychlorinated biphenyls (PCBs), as a member of persistent organic pollutants (POPs), have posed a risk to humans and the environment until today. The monitoring of phytotoxic PCB which is toxic to plants, is especially important for ecological early warning and pollution management. In this work, ß-cyclodextrin modified silver nanoparticles are prepared in a one-pot method, integrating the synthesis and surface modification in one step. The nanoparticles can supramolecularly immobilize 2,4,4'-trichlorobiphenyl (PCB 28) on their surface and construct a surface plasmon resonance-based nanosensor. Surface plasmon-resonance light scattering and surface-enhanced Raman scattering sensing of PCB 28 are realized using the nanosensor. The dual-modal sensing shows excellent performance for the potential practical monitoring of phytotoxic POPs in the plant and its growing environment.

Public acceptability of lumbar puncture in the diagnosis of Alzheimer's disease: a questionnaire-based single center study in China.

AIM: To investigate public acceptability of lumbar puncture in the diagnosis of Alzheimer's disease and to find out the factors influencing patient decision. METHODS: We administered a questionnaire to participants who were native to Xi'an using the "Sojump" application. Participants were required to answer the questionnaire on their cell phones following the instructions. The questions of the questionnaire were divided into four categories, including demographic data, awareness of lumbar puncture, attitudes toward lumbar puncture for the diagnosis of Alzheimer's disease, and reasons for negative attitude. Logistic regression was used to analyze the factors influencing the attitude toward lumbar puncture testing. RESULTS: A total of 1050 valid questionnaires were collected, including 403 (38.4%) from non-medical personnel and 647 (61.6%) from medical personnel. Among them, 35.7% of the participants knew about lumbar puncture examinations. Regarding the attitude, 862 participants (82.1%) had a positive attitude toward lumbar puncture in the diagnosis of Alzheimer's disease, and 508 (58.9%) of them considered lumbar puncture to be helpful in confirming the diagnosis. Multivariate analysis revealed that factors associated with a positive attitude in the non-medical group included age (OR=0.963, P=0.003, 95% CI: 0.939-0.987), education level (OR=2.073, P=0.037, 95% CI: 1.044-4.114), monthly income (OR=1.340, P=0.031, 95% CI: 1.028-1.748), and type of occupation (OR=1.569, P=0.038, 95% CI: 1.026-2.400). Factors associated with a positive attitude in the medical group included place of residence (OR=9.182, P=0.036, 95% CI: 1.151-73.238), monthly income (OR=4.008, P=0.002, 95% CI: 1.689-9.511), and hospital level (OR=38.311, P < 0.001, 95% CI: 14.323-102.478). CONCLUSIONS: More than 80% of the public has a positive attitude towards lumbar puncture in the diagnosis of Alzheimer's disease, suggesting high acceptability. However, the attitude toward lumbar puncture is depend on age, education level, economic status, and type of occupation.

Reduction-Active Antisolvent: A Universal and Innovative Strategy of Further Ameliorating Additive Optimization for High Efficiency Perovskite Solar Cells.

To further ameliorate current additive engineering of perovskites for viable applications, the inherent limitations should be overcome; these include weakened coordination of the dopants to the [PbI6]4- octahedra during crystallization and ubiquity of ineffective bonding sites. Herein, we introduce a facile strategy for synthesizing a reduction-active antisolvent. Washing with reduction-active PEDOT:PSS-blended antisolvent substantially enhances the intrinsic polarity of the Lewis acid (Pb2+) in [PbI6]4- octahedra, which causes significant strengthening of the coordinate bonding between additives and perovskite. Thus, coordination of the additive to the perovskite becomes much stable. Additionally, the enhanced coordination ability of Pb2+ can enhance the effective bonding sites and further enhance the efficacy of additive optimization to the perovskite. Here, we demonstrate five different additives as dopant bases and repeatedly verify the universality of this approach. The photovoltaic performance and stability of doped-MAPbI3 devices are further improved, revealing the advanced potential of additive engineering.

Flavor components detection and discrimination of isomers in Huaguo tea using headspace-gas chromatography-ion mobility spectrometry and multivariate statistical analysis.

Aroma components are one of the crucial factors in dynamic processes analysis, quality control, and origin traceability. Various categories of Huaguo Tea possessed different taste due to the generation of aroma. In this study, a comprehensive analysis of volatiles was conducted for five popular Huaguo Tea samples (Lemon Slices, Bitter Gourd Slices, Citri Reticulatae Pericarpium, Red Lycium Barbarum, and Black Lycium Barbarum) via gas chromatography-ion mobility spectrometry (GC-IMS) combining with multivariate statistical strategies. Comparison analysis was achieved with the properties of visually and intuitively by drawing of topography plots. A total of one hundred and eighty volatiles were distinguished. Aliphatic isomers were identified simultaneously by fingerprint spectra. Alcohols, aldehydes, esters, and ketones were the most abundant volatiles in Huaguo Tea samples. To characterize the Huaguo Tea precisely and establish an analysis model for their classification, multivariate statistical analysis was applied to distinguish different Huaguo Tea. Satisfied discrimination was obtained by principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA) based on the HS-GC-IMS results with the robustness parameter (R2Y) of 99.4%, and prediction ability parameter (Q2) of 98.6%, respectively. The results provide a theoretical basis for aroma discrimination, isomer identification, and categories analysis of Huaguo Tea.

Associations among Body Mass Index, Waist-to-Hip Ratio, and Cognitive Impairment Tend to Follow an Opposite Trend and Are Sex Specific: A Population-Based Cross-Sectional Study in a Rural Area of Xi'an, China.

INTRODUCTION: The relationship between obesity and cognitive impairment (CI) is highly heterogeneous in previous studies, which may be due to insufficient consideration of anthropometric indicators and sex. This study compared the cross-sectional relationships among body mass index (BMI), waist-to-hip ratio (WHR), and CI among people aged ≥40 years, and sex-specific relationships were also considered. METHODS: This was a population-based cross-sectional study with a cluster sampling design. CI was defined as a Mini-Mental State Examination score lower than the cutoff value. Multivariate logistic regression was used. BMI and WHR were fitted as both restricted cubic splines and categorical data. Stratified analysis and interaction analysis were performed to explore the sex-specific relationship. RESULTS: A total of 1,792 subjects (40.5% male) were analyzed, and 230 were confirmed to have CI. The relationships among BMI, WHR, and CI were significant (poverall = 0.023, pnonlinear = 0.097; poverall = 0.017, pnonlinear = 0.078, respectively) but exhibited an opposite trend in the total population in the analyses with BMI and WHR as restricted cubic splines. Further categorical analyses showed that subjects with a BMI <23 kg/m2 tended to have a higher risk of CI than those with BMI ≥23 kg/m2 (16.2% vs. 11.8%, p = 0.017; OR = 1.366 [0.969-1.926], p = 0.075), and subjects with a WHR >0.92 had a significantly higher risk of CI than those with a WHR ≤0.92 (11.7% vs. 16.2%, p = 0.011; OR = 1.619 [1.161-2.258], p = 0.005). In addition, the relationship between a low BMI and CI was more significant in males (p = 0.034), while the relationship between a high WHR and CI was more significant in females (p = 0.002). Further studies are needed to confirm the sex differences because of the marginal significance result in the interaction analysis (p = 0.051 for interaction term BMI × sex; p = 0.056 for interaction term WHR × sex). CONCLUSION: The relationships among BMI, WHR, and CI exhibit an opposite trend. A low BMI or high WHR was positively associated with CI, which was more prominent in males for a low BMI and females for a high WHR.

Delta and jagged are candidate target genes of RNAi biopesticides for the control of Nilaparvata lugens.

The brown planthopper (BPH; Nilaparvata lugens) is an important pest in rice cultivation, and chemical pesticide over-use and ineffectiveness of existing Bt transgenic rice against piercing-sucking insects make novel control methods necessary. RNA interference (RNAi) biopesticide is a new type of product with high efficiency and specificity and are simple to use. The Notch signaling pathway has extensive and important physiological functions and plays a key role in the development of insects. In this study, two key ligand genes of the Notch signaling pathway, delta (dl) and jagged (jag), were selected and their lethal effects and functional analysis were systematically evaluated using a stable short-winged population (Brachypterous strain) and a long-winged population (Macropterous strain) of BPHs. The full-length coding sequences of Nldl and Nljag comprised 1,863 and 3,837 base pairs, encoding 620 and 1,278 amino acids, respectively. The nucleic acid sequences of Nldl and Nljag were identical between the two strains. The expression levels of Nldl and Nljag were relatively high in the head of the nymphs, followed by those in the abdomen. Through RNAi treatment, we found that injection of BPH nymphs of both strains with dsNldl (10-50 ng/nymph) or dsNljag (100 ng/nymph) produced lethal or teratogenic effects. dsRNA treatment showed excellent inhibitory effects on the expression of target genes on days 1 and 5, suggesting that RNAi rapidly exhibits effects which persist for long periods of time in BPHs. Taken together, our results confirm the potential of Nldl and Nljag as target genes of RNAi biopesticides, and we propose optimized dosages for the control of BPHs.

Protocol of End-PSCI trial: a multicenter, randomized controlled trial to evaluate the effects of DL-3-n-butylphthalide on delayed-onset post stroke cognitive impairment.

BACKGROUND: Delayed-onset post stroke cognitive impairment (PSCI) results from secondary neurodegeneration induced by stroke. Whereas targeted prevention or treatment strategies are still missing due to lack of evidences. This trial aims to evaluate the preventive effects of DL-3-n-butylphthalide (NBP) on delayed-onset PSCI. METHODS: Effects of NBP on Delayed-onset Post Stroke Cognitive Impairment (End-PSCI) is a prospective, parallel-group, open-label, multicenter, randomized controlled trial with blinded outcome assessment. Hospital patients with acute cerebral infarction (within 2 weeks of onset) will be randomized into either standard medical therapy group or standard medical therapy combined NBP treatment group (NBP 200 mg, three times per day for 24 weeks). The primary outcome is the difference of incidence of delayed-onset PSCI between two groups. The secondary outcomes include difference of white matter degeneration, cognitive scores and prevalence of early-onset PSCI between two groups. DISCUSSION: End-PSCI trial will provide evidences for NBP preventing delayed-onset PSCI. The secondary outcomes will also provide valuable insights into the pathogenesis of delayed-onset PSCI and mechanism of NBP's actions. TRIAL REGISTRATION: Trialsearch.who.int , ChiCTR2000032555, 2020/5/2, prospectively registered.

Application progress of plant-mediated RNAi in pest control.

RNA interference (RNAi)-based biopesticides are novel biologic products, developed using RNAi principles. They are engineered to target genes of agricultural diseases, insects, and weeds, interfering with their target gene expression so as to hinder their growth and alleviate their damaging effects on crops. RNAi-based biopesticides are broadly classified into resistant plant-based plant-incorporated protectants (PIPs) and non-plant-incorporated protectants. PIP RNAi-based biopesticides are novel biopesticides that combine the advantages of RNAi and resistant transgenic crops. Such RNAi-based biopesticides are developed through nuclear or plastid transformation to breed resistant plants, i.e., dsRNA-expressing transgenic plants. The dsRNA of target genes is expressed in the plant cell, with pest and disease control being achieved through plant-target organism interactions. Here, we review the action mechanism and strategies of RNAi for pest management, the development of RNAi-based transgenic plant, and the current status and advantages of deploying these products for pest control, as well as the future research directions and problems in production and commercialization. Overall, this study aims to elucidate the current development status of RNAi-based biopesticides and provide guidelines for future research.