GLABRA 2 regulates ETHYLENE OVERPRODUCER 1 accumulation during nutrient deficiency-induced root hair growth.

Root hairs (RHs), extensive structures of root epidermal cells, are important for plant nutrient acquisition, soil anchorage, and environmental interactions. Excessive production of the phytohormone ethylene (ET) leads to substantial root hair growth, manifested as tolerance to plant nutrient deficiencies. However, the molecular basis of ET production during root hair growth in response to nutrient starvation remains unknown. Herein, we found that a critical transcription factor, GLABRA 2 (GL2), inhibits ET production during root hair growth in Arabidopsis (Arabidopsis thaliana). GL2 directly binds to the promoter of the gene encoding ET OVERPRODUCER 1 (ETO1), one of the most important ET-production-regulation factors, in vitro and in vivo, and then regulates the accumulation and function of ETO1 in root hair growth. The GL2-regulated-ETO1 module is required for promoting root hair growth under nitrogen, phosphorus, or potassium deficiency. Genome-wide analysis revealed numerous genes, such as ROOT HAIR DEFECTIVE 6-LIKE 4, ETHYLENE-INSENSITIVE 3-LIKE 2, ROOT HAIR SPECIFIC 13, are involved in the GL2-regulated-ETO1 module. Our work reveals a key transcription mechanism in the control of ET production during root hair growth under three major nutrient deficiencies.

Actin depolymerizing factor ADF7 inhibits actin bundling protein VILLIN1 to regulate root hair formation in response to osmotic stress in Arabidopsis.

Actin cytoskeleton is essential for root hair formation. However, the underlying molecular mechanisms of actin dynamics in root hair formation in response to abiotic stress are largely undiscovered. Here, genetic analysis showed that actin-depolymerizing protein ADF7 and actin-bundling protein VILLIN1 (VLN1) were positively and negatively involved in root hair formation of Arabidopsis respectively. Moreover, RT-qPCR, GUS staining, western blotting, and genetic analysis revealed that ADF7 played an important role in inhibiting the expression and function of VLN1 during root hair formation. Filament actin (F-actin) dynamics observation and actin pharmacological experiments indicated that ADF7-inhibited-VLN1 pathway led to the decline of F-actin bundling and thick bundle formation, as well as the increase of F-actin depolymerization and turnover to promote root hair formation. Furthermore, the F-actin dynamics mediated by ADF7-inhibited-VLN1 pathway was associated with the reactive oxygen species (ROS) accumulation in root hair formation. Finally, ADF7-inhibited-VLN1 pathway was critical for osmotic stress-induced root hair formation. Our work demonstrates that ADF7 inhibits VLN1 to regulate F-actin dynamics in root hair formation in response to osmotic stress, providing the novel evidence on the F-actin dynamics and their molecular mechanisms in root hair formation and in abiotic stress.

Antiferroelectric Heterostructures Memristors with Unique Resistive Switching Mechanisms and Properties.

A novel antiferroelectric material, PbSnO3 (PSO), was introduced into a resistive random access memory (RRAM) to reveal its resistive switching (RS) properties. It exhibits outstanding electrical performance with a large memory window (>104), narrow switching voltage distribution (±2 V), and low power consumption. Using high-resolution transmission electron microscopy, we observed the antiferroelectric properties and remanent polarization of the PSO thin films. The in-plane shear strains in the monoclinic PSO layer are attributed to oxygen octahedral tilts, resulting in misfit dislocations and grain boundaries at the PSO/SRO interface. Furthermore, the incoherent grain boundaries between the orthorhombic and monoclinic phases are assumed to be the primary paths of Ag+ filaments. Therefore, the RS behavior is primarily dominated by antiferroelectric polarization and defect mechanisms for the PSO structures. The RS behavior of antiferroelectric heterostructures controlled by switching spontaneous polarization and strain, defects, and surface chemistry reactions can facilitate the development of new antiferroelectric device systems.

Insulin resistance and coronary inflammation in patients with coronary artery disease: a cross-sectional study.

BACKGROUND: Insulin resistance (IR) is associated with coronary artery disease (CAD) severity. However, its underlying mechanisms are not fully understood. Therefore, our study aimed to explore the relationship between IR and coronary inflammation and investigate the synergistic and mediating effects of coronary inflammation on the association between IR and CAD severity. METHODS: Consecutive patients with CAD who underwent coronary angiography and coronary computed tomography angiography between April 2018 and March 2023 were enrolled. The triglyceride-glucose index (TyG index) and peri-coronary adipose tissue (PCAT) attenuation around the proximal right coronary artery (RCA) were used to evaluate IR and coronary inflammation, respectively. The correlation between the TyG index and PCAT attenuation was analyzed using linear regression models. Logistic regression models were further used for investigating the correlation of the TyG index and PCAT attenuation with CAD severity. A mediation analysis assessed the correlation between IR and CAD severity mediated by coronary inflammation. RESULTS: A total of 569 participants (mean age, 62 ± 11 years; 67.8% men) were included in the study. PCAT attenuation was positively associated with the TyG index (r = 0.166; P < 0.001). After adjusting for potential confounders, the per standard deviation increment in the TyG index was associated with a 1.791 Hounsfield unit (HU) increase (95% confidence interval [CI], 0.920-2.662 HU; P < 0.001) in the PCAT attenuation. In total, 382 (67.1%) patients had multivessel CAD. The patients in the high-TyG index/high PCAT attenuation group had approximately 3.2 times the odds of multivessel CAD compared with those in the low-TyG index/low PCAT attenuation group (odds ratio, 3.199; 95%CI, 1.826-5.607; P < 0.001). Mediation analysis indicated that PCAT attenuation mediated 31.66% of the correlation between the TyG index and multivessel CAD. CONCLUSIONS: The TyG index positively correlated with PCAT attenuation in patients with CAD. The TyG index and PCAT attenuation showed a synergistic correlation with multivessel CAD. Furthermore, PCAT attenuation partially mediated the relationship between the TyG index and CAD severity. Controlling inflammation in patients with high IR and coronary inflammation may provide additional benefits.

Beyond brain injury: Examining the neuropsychological and psychosocial sequelae of post-traumatic epilepsy.

OBJECTIVE: This study investigates neuropsychological and psychosocial outcomes in patients with traumatic brain injury (TBI) and post-traumatic epilepsy (PTE) compared to a healthy control group. METHOD: Utilizing a quasi-experimental cross-sectional design, the research involved patients with TBI and PTE referred from a Taiwanese medical center. An age- and education-matched control group of healthy adults without traumatic injuries was also recruited. The study involved analyzing retrospective medical records and applying a comprehensive suite of neuropsychological tests and psychosocial questionnaires. RESULTS: Executive function measures revealed significantly reduced performance in both the TBI and PTE groups compared to controls. Specifically, the MoCA scores were lowest in the PTE group, followed by the TBI group, and highest in the controls. Measures of subjective symptomatology showed comparably elevated levels in both the TBI and PTE groups relative to controls. CONCLUSION: The research suggests that PTE may intensify the difficulties faced by individuals with TBI, but its impact on overall recovery might not be significant, considering the trajectory of the brain injury itself. Notably, the MoCA results indicate that cognitive deficits are more pronounced in PTE patients compared to those with TBI, underscoring the necessity for targeted neuropsychological assessments. Further investigation is essential to explore PTE's broader neuropsychological and psychosocial impacts. These findings advocate for tailored care strategies that address both neuropsychological and psychosocial needs, ensuring comprehensive management of TBI and PTE.

Breast cancer therapy: from the perspective of glucose metabolism and glycosylation.

Breast cancer is a leading cause of mortality and the most prevalent form of malignant tumor among women worldwide. Breast cancer cells exhibit an elevated glycolysis and altered glucose metabolism. Moreover, these cells display abnormal glycosylation patterns, influencing invasion, proliferation, metastasis, and drug resistance. Consequently, targeting glycolysis and mitigating abnormal glycosylation represent key therapeutic strategies for breast cancer. This review underscores the importance of protein glycosylation and glucose metabolism alterations in breast cancer. The current research efforts in developing effective interventions targeting glycolysis and glycosylation are further discussed.

Association between oxidative balance score and resistant hypertension and arterial stiffness among US adults: A population-based study.

BACKGROUND AND AIMS: Prior studies have established the correlation between oxidative balance score (OBS) and hypertension (HTN). While the association between OBS and resistant hypertension (RHT) as well as arterial stiffness among individuals with hypertension remains undisclosed. METHODS AND RESULTS: In this study, total of 15,910 adults diagnosed with hypertension were enrolled from NHANES 2001-2018. OBS was calculated and categorized into quartiles. Weighted regression model, stratified analyses and restricted cubic spline (RCS) were employed to evaluate the association between OBS and RHT, major adverse cardiovascular events (MACEs) and arterial stiffness in individuals with hypertension. Among enrolled participants, high OBS quartiles consistently demonstrated a negative association with resistant hypertension across all models (all p < 0.05), indicating robust stability. Compared with the lowest OBS quartile, the risk of resistant hypertension in the highest OBS quartile was decreased by 30.8% (95%CI 0.471-0.995, p = 0.049). After dividing OBS into dietary OBS and lifestyle OBS, a significant inverse association with lifestyle OBS and RHT was observed. With regard to MACEs, the inverse association was also found in participants with high OBS. Besides, the potential relation between OBS and arterial stiffness was explored and we found OBS was significantly associated with decreased arterial stiffness (ß for ePWV, -0.014; 95%CI -0.026 to -0.001; p = 0.032). RCS analysis confirmed a nonlinear association between OBS and RHT, MACEs, cardiovascular death and nonfatal MI among participants with hypertension. CONCLUSION: Elevated OBS was negatively associated with the risk of RHT and arterial stiffness among US adults with hypertension.

Association between the incident hypertension duration and cognitive performance in older adults: data from the NHANES 2011-2014.

BACKGROUND: Established evidences have demonstrated that hypertension was associated with the cognitive impairment. But the associations between the duration of hypertension exposure and cognitive performance are still inconclusive. OBJECTIVES: The objective of this study was to assess the association between the duration of hypertension diagnosis and cognitive performance in older adults by the National Health and Nutrition Examination Survey (2011-2014). METHODS: To evaluate the relationship between the hypertension duration and cognitive performance, we conducted the logistic regression analysis. Furthermore, we also performed the Restricted cubic spline (RCS) analysis to assess the nonlinear relationship between the duration of exposure to hypertension and cognitive performance. RESULTS: Initially, total 19,931 participants were included in this study, and 2928 individuals were enrolled. With the increase of hypertension duration, more risk of cognitive impairment was observed in the Digit Symbol Substitution test (DSST) (OR = 1.012, 1.006-1.019), and a similar trend was observed in Animal Fluency test (AFT) (OR = 1.009,1.003-1.016). The RCS results showed that the hypertension duration pattern was linear associated with the risk of cognitive impairment in DDST (P for non-linearity = 0.758). Meanwhile, subgroups analysis of midlife hypertension, we revealed that linear association with the risk of cognitive impairment in DSST (P for non-linearity = 0.391) and CERAD (P for non-linearity = 0.849) among hypertension diagnose < 55 years populations. CONCLUSION: Collectively, our finding indicates that longer duration of exposure to hypertension worsens the cognition performance, especially for middle-aged hypertension.

Hyperbaric Oxygen Therapy Reduces the Traumatic Brain Injury-Mediated Neuroinflammation Through Enrichment of Prevotella Copri in the Gut of Male Rats.

BACKGROUND: Gastrointestinal dysfunction frequently occurs following traumatic brain injury (TBI) and significantly increases posttraumatic complications. TBI can lead to alterations in gut microbiota. The neuroprotective effects of hyperbaric oxygen (HBO) have not been well recognized after TBI. The study''s aim was to investigate the impact of HBO on TBI-induced dysbiosis in the gut and the pathological changes in the brain following TBI. METHODS: Anesthetized male Sprague-Dawley rats were randomly assigned to three groups: sham surgery plus normobaric air (21% oxygen at 1 atmospheres absolute), TBI (2.0 atm) plus normobaric air, and TBI (2.0 atm) plus HBO (100% oxygen at 2.0 atmospheres absolute) for 60 min immediately after TBI, 24 h later, and 48 h later. The brain injury volume, tumor necrosis factor-α expression in microglia and astrocytes, and neuronal apoptosis in the brain were subsequently determined. The V3-V4 regions of 16S ribosomal rRNA in the fecal samples were sequenced, and alterations in the gut microbiome were statistically analyzed. All parameters were evaluated on the 3rd day after TBI. RESULTS: Our results demonstrated that HBO improved TBI-induced neuroinflammation, brain injury volume, and neuronal apoptosis. HBO appeared to increase the abundance of aerobic bacteria while inhibiting anaerobic bacteria. Intriguingly, HBO reversed the TBI-mediated decrease in Prevotella copri and Deinococcus spp., both of which were negatively correlated with neuroinflammation and brain injury volume. TBI increased the abundance of these gut bacteria in relation to NOD-lik0065 receptor signaling and the proteasome pathway, which also exhibited a positive correlation trend with neuro inflammation and apoptosis. The abundance of Prevotella copri was negatively correlated with NOD-like receptor signaling and the Proteasome pathway. CONCLUSIONS: Our study demonstrated how the neuroprotective effects of HBO after acute TBI might act through reshaping the TBI-induced gut dysbiosis and reversing the TBI-mediated decrease of Prevotella copri.

Dynamics of Actin Filaments Play an Important Role in Root Hair Growth under Low Potassium Stress in Arabidopsis thaliana.

Potassium (K) is an essential nutrient for the growth and development of plants. Root hairs are the main parts of plants that absorb K+. The regulation of plant root hair growth in response to a wide range of environmental stresses is crucially associated with the dynamics of actin filaments, and the thick actin bundles at the apical and sub-apical regions are essential for terminating the rapid elongation of root hair cells. However, the dynamics and roles of actin filaments in root hair growth in plants' response to low K+ stress are not fully understood. Here, we revealed that root hairs grow faster and longer under low K+ stress than the control conditions. Compared to control conditions, the actin filaments in the sub-apex of fast-growing wild-type root hairs were longer and more parallel under low K+ stress, which correlates with an increased root hair growth rate under low K+ stress; the finer actin filaments in the sub-apex of the early fully grown Col-0 root hairs under low K+ stress, which is associated with low K+ stress-induced root hair growth time. Further, Arabidopsis thaliana actin bundling protein Villin1 (VLN1) and Villin4 (VLN4) was inhibited and induced under low K+ stress, respectively. Low K+ stress-inhibited VLN1 led to decreased bundling rate and thick bundle formation in the early fully grown phase. Low K+ stress-induced VLN4 functioned in keeping long filaments in the fast-growing phase. Furthermore, the analysis of genetics pointed out the involvement of VLN1 and VLN4 in the growth of root hairs under the stress of low potassium levels in plants. Our results provide a basis for the dynamics of actin filaments and their molecular regulation mechanisms in root hair growth in response to low K+ stress.

Chinese Herbal Medicines as Natural Alternative Products to Antibiotics in Weaned Piglets through Intestinal Microbiota Regulation.

During the growth process of weaned piglets, digestive problems such as gastrointestinal disorders and diarrhea are common. Farmers usually use antibiotics to help piglets grow smoothly. However, the overuse of antibiotics can lead to antibiotic resistance issues. Therefore, this study chose to use plant extracts as feed additives to explore their potential as alternatives to antibiotics. Additionally, Tilmicosin was used as the antibiotic because it is widely used in treating respiratory infections in piglets. Since traditional Chinese medicine often uses natural products, we selected Guizhi Li-Zhong (GLZ) extract as an alternative to antibiotics. The experiment involved 126 piglets, each 4 weeks old, which were randomly assigned to one of four groups: the sham group (basal diet without supplements, 10.3 ± 0.4 kg, n = 31), the low-dose GLZ group (basal diet with 0.05% GLZ, 10.9 ± 0.4 kg, n = 32), the regular-dose GLZ group (basal diet with 0.2% GLZ, 10.6 ± 0.4 kg, n = 32), and the regular-dose Tilmicosin antibiotic group (basal diet with 0.2% Tilmicosin, 10.2 ± 0.3 kg, n = 31). We recorded and compared the survival rate, growth rate, feed conversion ratio, and diarrhea incidence among four groups of weaned piglets from the 4th to the 10th weeks of age. Then, we examined the oxidative stress, inflammation, and apoptosis in small intestine tissue (jejunum and ileum) through immunohistochemistry and Western blot and compared the gut microbiota in large intestine tissue (colon and rectum) through a next-generation sequencing (NGS) analysis. Our results showed that weaned piglets supplemented with 0.05% and 0.2% GLZ had better survival rates, growth rates (p < 0.01), and feed conversion ratios (p < 0.01) compared to those receiving sham treatment. Even weaned piglets supplemented with 0.2% GLZ performed better than those supplemented with 0.2% Tilmicosin antibiotics (p < 0.05). Furthermore, the incidence of diarrhea and small intestine injury (indicated by oxidative stress-, inflammation-, and apoptosis-related proteins) in piglets supplemented with 0.05% and 0.2% GLZ was lower than in piglets receiving sham treatment (p < 0.05). Even piglets supplemented with 0.2% GLZ had less injury than those supplemented with 0.2% Tilmicosin antibiotics (p < 0.05). The NGS results further showed that GLZ treatment significantly improved beneficial bacteria in weaned piglets (p < 0.05), while antibiotic treatment reduced beneficial bacteria (p < 0.05). In summary, we recommend adding GLZ to the feed as an alternative to antibiotics. This not only effectively reduces intestinal damage but also improves the gut microbiota, thereby promoting the growth of weaning piglets.

Hyperuricemia as an independent risk factor for metabolic dysfunction-associated fatty liver disease in nonobese patients without type 2 diabetes mellitus.

According to the latest consensus statement, fatty liver complicated by specific metabolic abnormalities can be diagnosed as metabolic dysfunction-associated fatty liver disease (MAFLD) in nonobese patients without type 2 diabetes mellitus (T2DM). However, hyperuricemia (HUA), a manifestation of metabolic disorders, is excluded from diagnostic criteria. This study explored the association between HUA and MAFLD in nonobese patients without T2DM. A total of 28,187 participants were recruited from the Examination Center of the China-Japan Friendship Hospital from 2018 to 2022 and divided into four subgroups: nonobese patients without T2DM, obese patients without T2DM, nonobese patients with T2DM, and obese patients with T2DM. MAFLD was diagnosed by ultrasound combined with laboratory examinations. The association of HUA with MAFLD subgroups was performed by logistical regression analysis. The predictive ability of UA for MAFLD subgroups was assessed by receiver operating characteristics (ROC). HUA was positively associated with MAFLD in nonobese patients without T2DM in both males and females, even after adjusting for sex, BMI, dyslipidemia, and abnormal liver function. The association increased gradually with aging, especially in those over 40 yr old. HUA was an independent risk factor for MAFLD in nonobese patients without T2DM. We suggest that UA abnormalities might be considered in the diagnosis of MAFLD in nonobese patients without T2DM.NEW & NOTEWORTHY HUA is an independent risk factor for MAFLD in nonobese patients without T2DM. The association of HUA with MAFLD in nonobese patients without T2DM increased gradually with aging, especially in those over 40 yr old. In nonobese patients without T2DM, univariate analysis showed that females with HUA had a higher risk of MAFLD than males. However, the difference was narrowed after adjustment for confounders.

Core Protein-Directed Antivirals and Importin ß Can Synergistically Disrupt Hepatitis B Virus Capsids.

Viral structural proteins can have multiple activities. Antivirals that target structural proteins have potential to exhibit multiple antiviral mechanisms. Hepatitis B virus (HBV) core protein (Cp) is involved in most stages of the viral life cycle; it assembles into capsids, packages viral RNA, is a metabolic compartment for reverse transcription, interacts with nuclear trafficking machinery, and disassembles to release the viral genome into the nucleus. During nuclear localization, HBV capsids bind to host importins (e.g., Impß) via Cp's C-terminal domain (CTD); the CTD is localized to the interior of the capsid and is transiently exposed on the exterior. We used HAP12 as a representative Cp allosteric modulator (CpAM), a class of antivirals that inappropriately stimulates and misdirects HBV assembly and deforms capsids. CpAM impact on other aspects of the HBV life cycle is poorly understood. We investigate how HAP12 influences the interactions between empty or RNA-filled capsids with Impß and trypsin in vitro. We show that HAP12 can modulate CTD accessibility and capsid stability, depending on the saturation of HAP12-binding sites. We demonstrate that Impß synergistically contributes to capsid disruption at high levels of HAP12 saturation, using electron microscopy to visualize the disruption and rearrangement of Cp dimers into aberrant complexes. However, RNA-filled capsids resist the destabilizing effects of HAP12 and Impß. In summary, we show host protein-induced catalysis of capsid disruption, an unexpected additional mechanism of action for CpAMs. Potentially, untimely capsid disassembly can hamper the HBV life cycle and also cause the virus to become vulnerable to host innate immune responses. IMPORTANCE The HBV core, an icosahedral complex of 120 copies of the homodimeric core (capsid) protein with or without packaged nucleic acid, is transported to the host nucleus by its interaction with host importin proteins. Importin-core interaction requires the core protein C-terminal domain, which is inside the capsid, to "flip" to the capsid exterior. Core protein-directed drugs that affect capsid assembly and stability have been developed recently. We show that these molecules can, synergistically with importins, disrupt capsids. This mechanism of action, synergism with host protein, has the potential to disrupt the virus life cycle and activate the innate immune system.

A robust adiabatic constant amplitude spin-lock preparation module for myocardial T1ρ quantification at 3 T.

T1ρ quantification has the potential to assess myocardial fibrosis without contrast agent. However, its preparation spin-lock pulse is sensitive to B1 and B0 inhomogeneities, resulting in severe banding artifacts in the heart region, especially at high magnetic field such as 3 T. We aimed to design a robust spin-lock (SL) preparation module that can be used in myocardial T1ρ quantification at 3 T. We used the tan/tanh pulse to tip up and tip down the magnetization in the spin-lock preparation module (tan/tanh-SL). Bloch simulation was used to optimize pulse shape parameters of the tan/tanh with a pulse duration (Tp ) of 8, 4, and 2 ms, respectively. The designed tan/tanh-SL modules were implemented on a 3-T MR scanner. They were evaluated in phantom studies under three different cases of B0 and B1 inhomogeneities, and tested in cardiac T1ρ quantification of healthy volunteers. The performance of the tan/tanh-SL was compared with the composite SL preparation pulses and the commonly used hyperbolic secant pulse for spin-lock (HS-SL). Feasible pulse shape parameters were obtained using Bloch simulation. Compared with HS-SL, the quantification error of tan/tanh-SL was reduced by 27.7% for Tp = 8 ms (mean ∆Q = 126.15 vs. 174.42) and 75.6% for Tp = 4 ms (mean ∆Q = 136.65 vs. 559.53). In the phantom study, tan/tanh-SL was less sensitive to B1 and B0 inhomogeneity compared with composite SL pulses and HS-SL. In cardiac T1ρ quantification, the T1ρ maps using tan/tanh-SL showed fewer banding artifacts than using composite SL pulses and HS-SL. The proposed tan/tanh-SL preparation module greatly improves the robustness to B0 and B1 field inhomogeneities and can be used in cardiac T1ρ quantification at 3 T.

Pharmacological and Behavioral Interventions for Fatigue in Parkinson's Disease: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: This study aims to evaluate pharmacological and behavioral interventions for the treatment of fatigue in Parkinson's disease (PD) patients. METHODS: We systematically searched PubMed, PsycINFO, Web of Science, EMBASE, CNKI, Wan fang, and VIP up to July 31, 2022. We used Revman 5.3 software for the meta-analysis. The outcomes included Fatigue Severity Scale (FSS) and Parkinson's Fatigue Scale (PFS). The mean difference (MD) and 95% confidence intervals (CI) were collected or calculated. RESULTS: Thirteen randomized controlled trials (RCTs) with a total of 1758 patients were included. The meta-analysis showed that current clinical treatments reduced FSS (MD: -1.60, 95% CI: -3.14 to -0.05) and PFS (MD: -0.61, 95% CI: -1.17 to -0.05) in patients with PD. Subgroup meta-analysis showed that: (1) neither pharmacological interventions nor behavioral interventions reduced FSS in PD patients; (2) dopaminergic drugs dose-dependently significantly reduced the PFS in patients with PD; (3) behavioral interventions have an almost significant effect (MD: -6.69, 95% CI: -13.71 to 0.33, P = 0.06, I2 = 74%) on alleviating PFS in PD patients; (4) vestibular rehabilitation training significantly reduced the PFS in patients with PD. CONCLUSIONS: Current clinical treatments alleviate fatigue in PD patients. Dopaminergic drugs may act a stronger effect than amphetamines. Behavioral interventions, especially vestibular rehabilitation training, may be a promising way for the treatment of fatigue in patients with PD though further evidence is still needed.

Global COVID-19 pandemic demands joint interventions for the suppression of future waves.

Emerging evidence suggests a resurgence of COVID-19 in the coming years. It is thus critical to optimize emergency response planning from a broad, integrated perspective. We developed a mathematical model incorporating climate-driven variation in community transmissions and movement-modulated spatial diffusions of COVID-19 into various intervention scenarios. We find that an intensive 8-wk intervention targeting the reduction of local transmissibility and international travel is efficient and effective. Practically, we suggest a tiered implementation of this strategy where interventions are first implemented at locations in what we call the Global Intervention Hub, followed by timely interventions in secondary high-risk locations. We argue that thinking globally, categorizing locations in a hub-and-spoke intervention network, and acting locally, applying interventions at high-risk areas, is a functional strategy to avert the tremendous burden that would otherwise be placed on public health and society.

Atomic Imaging and Thermally Induced Dynamic Structural Evolution of Two-Dimensional Cr2S3.

In this study, facile salt-assisted chemical vapor deposition (CVD) was used to synthesize ultrathin non-van der Waals chromium sulfide (Cr2S3) with a thickness of ∼1.9 nm. The structural transformation of as-grown Cr2S3 was studied using advanced in situ heating techniques combined with transmission electron microscopy (TEM). Two-dimensional (2D) and quasi-one-dimensional (1D) samples were fabricated to investigate the connection between specific planes and the dynamic behavior of the structural variation. The rearrangement of atoms during the phase transition was driven by the loss of sulfur atoms at elevated temperatures, resulting in increased free energy. A decrease in the ratio of the (001) plane led to an overall increase in surface energy, thus lowering the critical phase transition temperature. Our study provides detailed insight into the mechanism of structural transformation and the critical factors governing transition temperature, thus paving the way for future studies on intriguing Cr-S compounds.

BrCWM Mutation Disrupted Leaf Flattening in Chinese Cabbage (Brassica rapa L. ssp. pekinensis).

Leaf flattening plays a vital role in the establishment of plant architecture, which is closely related to plant photosynthesis and, thus, influences the product yield and quality of Chinese cabbage. In this study, we used the doubled haploid line 'FT' of Chinese cabbage as the wild type for ethyl methanesulfonate (EMS) mutagenesis and obtained a mutant cwm with stably inherited compact and wrinkled leaves. Genetic analysis revealed that the mutated trait was controlled by a single recessive nuclear gene, Brcwm. Brcwm was preliminarily mapped to chromosome A07 based on bulked segregant RNA sequencing (BSR-seq) and fine-mapped to a 205.66 kb region containing 39 genes between Indel12 and Indel21 using SSR and Indel analysis. According to the whole-genome re-sequencing results, we found that there was only one nonsynonymous single nucleotide polymorphism (SNP) (C to T) within the target interval on exon 4 of BraA07g021970.3C, which resulted in a proline to serine amino acid substitution. The mutated trait co-segregated with the SNP. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) revealed that BraA07g021970.3C expression was dramatically higher in 'FT' leaves than that in cwm leaves. BraA07g021970.3C is homologous to AT3G55000 encoding a protein related to cortical microtubule organization. A similar phenotype of dwarfism and wrinkled leaves was observed in the recessive homozygous mutant cwm-f1 of AT3G55000, and its T3 transgenic lines were restored to the Arabidopsis wild-type phenotype through ectopic overexpression of BraA07g021970.3C. These results verified that BraA07g021970.3C was the target gene essential for leaf flattening in Chinese cabbage.

Actin Depolymerization Factor ADF1 Regulated by MYB30 Plays an Important Role in Plant Thermal Adaptation.

Actin filaments are essential for plant adaptation to high temperatures. However, the molecular mechanisms of actin filaments in plant thermal adaptation remain unclear. Here, we found that the expression of Arabidopsis actin depolymerization factor 1 (AtADF1) was repressed by high temperatures. Compared with wild-type seedlings (WT), the mutation of AtADF1 and the overexpression of AtADF1 led to promoted and inhibited plant growth under high temperature conditions, respectively. Further, high temperatures induced the stability of actin filaments in plants. Compared with WT, Atadf1-1 mutant seedlings showed more stability of actin filaments under normal and high temperature conditions, while the AtADF1 overexpression seedlings showed the opposite results. Additionally, AtMYB30 directly bound to the promoter of AtADF1 at a known AtMYB30 binding site, AACAAAC, and promoted the transcription of AtADF1 under high temperature treatments. Genetic analysis further indicated that AtMYB30 regulated AtADF1 under high temperature treatments. Chinese cabbage ADF1 (BrADF1) was highly homologous with AtADF1. The expression of BrADF1 was inhibited by high temperatures. BrADF1 overexpression inhibited plant growth and reduced the percentage of actin cable and the average length of actin filaments in Arabidopsis, which were similar to those of AtADF1 overexpression seedlings. AtADF1 and BrADF1 also affected the expression of some key heat response genes. In conclusion, our results indicate that ADF1 plays an important role in plant thermal adaptation by blocking the high-temperature-induced stability of actin filaments and is directly regulated by MYB30.

Targeting Chondroitin Sulphate Synthase 1 (Chsy1) Promotes Axon Growth Following Neurorrhaphy by Suppressing Versican Accumulation.

Versican is a chondroitin sulfate proteoglycan (CSPG), which deposits in perineurium as a physical barrier and prevents the growth of axons out of the fascial boundary. Several studies have indicated that the chondroitin sulfate (CS) chains on versican have several possible functions beyond the physical barrier, including the ability to stabilize versican core protein in the extracellular matrix. As chondroitin sulfate synthase 1 (Chsy1) is a crucial enzyme for CS elongation, we hypothesized that in vivo knockdown of Chsy1 at peripheral nerve lesion site may decrease CS and versican accumulation, and result in accelerating neurite regeneration. In the present study, end-to-side neurorrhaphy (ESN) in Wistar rats was used as an in vivo model of peripheral nerve injury to evaluate nerve regeneration after surgical intervention. The distribution and expression of versican and Chsy1 in regenerating axons after ESN was studied using confocal microscopy and western blotting. Chsy1 was silenced at the nerve lesion (surgical) site using in vivo siRNA transfection. The results indicated that Chsy1 was successfully silenced in nerve tissue, and its downregulation was associated with functional recovery of compound muscle action potential. Silencing of Chsy1 also decreased the accumulation of versican core protein, suggesting that transient treating of Chsy1-siRNA may be an alternative and an effective strategy to promote injured peripheral nerve regeneration.