Risk Factors of Failed Conservative Treatment for Adjacent Vertebral Fractures Following Percutaneous Vertebroplasty.

STUDY DESIGN: A retrospective, single-center, observational study. OBJECTIVE: This study investigated the risk factors associated with the failure of conservative treatment for adjacent vertebral fractures (AVFs). SUMMARY OF BACKGROUND DATA: Adjacent vertebral fractures following vertebroplasty for osteoporotic vertebral compression fractures are not uncommon. Presently, there is a lack of consensus regarding the management of adjacent vertebral fractures. METHODS: We included patients who developed adjacent vertebral fractures within two years post single-level vertebroplasty between January 2013 and December 2020. All patients initially underwent six weeks of conservative treatment, including pain medications, bracing, and physical therapy. Surgical intervention was offered to those with intractable back pain due to AVFs. Baseline demographics, AVF characteristics, and radiological measurements were systematically collected, and sequential univariable and multivariable logistic regression analyses were conducted to explore the risk factors. RESULTS: Of the 114 patients with a mean age of 78.6 years, two-thirds (76 patients) tolerated conservative treatment well, while 38 required surgical interventions for adjacent vertebral fractures. Both groups demonstrated similar baseline demographics and radiological parameters regarding AVFs (P>0.05). The multivariable logistic regression analyses revealed that the development of AVFs later than six months post-vertebroplasty and their caudal location to the index vertebroplasty were the independent risk factors of unsuccessful conservative treatment, with odds ratios of 3.57 (95% confidence interval [CI]: 1.14-11.1, P=0.029) and 2.50 (95% CI: 1.09-5.88, P=0.032), respectively. CONCLUSION: Adjacent vertebral fractures following percutaneous vertebroplasty generally have favorable outcomes under conservative treatment. However, the timing and the relative anatomical location of adjacent vertebral fractures are associated with treatment efficacy. Adjacent vertebral fractures occurring later than six months following the initial vertebroplasty or situated in the caudal location to the index vertebroplasty may exhibit reduced responsiveness to conservative treatment. These patients might benefit from a more aggressive therapeutic approach. LEVEL OF EVIDENCE: 3.

An examination of the impact of unmelted, melted, and deconstructed cheese on lipid metabolism: a 6-week randomised trial.

Background: Evidence suggests cheese has a favourable or neutral effect on cardiometabolic health, compared to butter. To date, studies have only considered the cheese matrix in its unmelted form, while the effect of melted cheese remains unknown. Objective: To test the effect of 6-week daily consumption of ∼40 g dairy fat, eaten in either as unmelted cheese, melted cheese, or in a fully deconstructed form, on markers of metabolic health in overweight adults aged ≥50 years of age. Design: A 6-week randomised parallel intervention, where 162 participants (43.3% male) received ∼40 g of dairy fat per day, in 1 of 3 treatments: (A) 120 g full-fat Irish grass-fed cheddar cheese, eaten in unmelted form (n 58); (B) 120 g full-fat Irish grass-fed cheddar cheese eaten in melted form (n 53); or (C) the equivalent components; butter (49 g), calcium caseinate powder (30 g), and Ca supplement (CaCO3; 500 mg) (n 51). Results: There was no difference in weight, fasting glucose, or insulin between the groups post-intervention. Melted cheese, compared to unmelted cheese, increased total cholesterol (0.23 ± 0.79 mmol L-1vs. 0.02 ± 0.67 mmol L-1, P = 0.008) and triglyceride concentrations (0.17 ± 0.39 mmol L-1vs. 0.00 ± 0.42 mmol L-1, P = 0.016). Melted cheese increased total cholesterol concentrations by 0.20 ± 0.15 mmol L-1 and triglyceride concentrations by 0.17 ± 0.08 mmol L-1 compared to unmelted cheese. No significant differences were observed between the cheese forms for change in HDL, LDL or VLDL cholesterol. Conclusion: Compared to unmelted cheese, melted cheese was found to increase total cholesterol and triglyceride concentrations in middle-aged, overweight adults with no effect on weight or glycaemic control.

Differential phosphorylation of Ca2+-permeable channel CNGC20 modulates calcium-mediated freezing tolerance in Arabidopsis.

Plants respond to cold stress at multiple levels, including increasing cytosolic calcium (Ca2+) influx and triggering the expression of cold-responsive genes. Here we show that the Ca2+-permeable channel CYCLIC NUCLEOTIDE GATED CHANNEL20 (CNGC20) positively regulates freezing tolerance in Arabidopsis (Arabidopsis thaliana) by mediating cold-induced Ca2+ influx. Moreover, we demonstrate that the leucine-rich repeat receptor-like kinase PLANT PEPTIDE CONTAINING SULFATED TYROSINE1 RECEPTOR (PSY1R) is activated by cold, phosphorylating and enhancing the activity of CNGC20. The psy1r mutant exhibited decreased cold-evoked Ca2+ influx and freezing tolerance. Conversely, COLD-RESPONSIVE PROTEIN KINASE1 (CRPK1), a protein kinase that negatively regulates cold signaling, phosphorylates and facilitates the degradation of CNGC20 under prolonged periods of cold treatment, thereby attenuating freezing tolerance. This study thus identifies PSY1R and CRPK1 kinases that regulate CNGC20 activity and stability, respectively, thereby antagonistically modulating freezing tolerance in plants.

Ca2+-independent ZmCPK2 is inhibited by Ca2+-dependent ZmCPK17 during drought response in maize.

Calcium oscillations are induced by different stresses. Calcium-dependent protein kinases (CDPKs/CPKs) are one major group of the plant calcium decoders that are involved in various processes including drought response. Some CPKs are calcium-independent. Here, we identified ZmCPK2 as a negative regulator of drought resistance by screening an overexpression transgenic maize pool. We found that ZmCPK2 does not bind calcium, and its activity is mainly inhibited during short term abscisic acid (ABA) treatment, and dynamically changed in prolonged treatment. Interestingly, ZmCPK2 interacts with and is inhibited by calcium-dependent ZmCPK17, a positive regulator of drought resistance, which is activated by ABA. ZmCPK17 could prevent the nuclear localization of ZmCPK2 through phosphorylation of ZmCPK2T60. ZmCPK2 interacts with and phosphorylates and activates ZmYAB15, a negative transcriptional factor for drought resistance. Our results suggest that drought stress-induced Ca2+ can be decoded directly by ZmCPK17 that inhibits ZmCPK2, thereby promoting plant adaptation to water deficit.

Phosphorylation of ZmAL14 by ZmSnRK2.2 regulates drought resistance through derepressing ZmROP8 expression.

Drought stress has negative effects on crop growth and production. Characterization of transcription factors that regulate the expression of drought-responsive genes is critical for understanding the transcriptional regulatory networks in response to drought, which facilitates the improvement of crop drought tolerance. Here, we identified an Alfin-like (AL) family gene ZmAL14 that negatively regulates drought resistance. Overexpression of ZmAL14 exhibits susceptibility to drought while mutation of ZmAL14 enhances drought resistance. An abscisic acid (ABA)-activated protein kinase ZmSnRK2.2 interacts and phosphorylates ZmAL14 at T38 residue. Knockout of ZmSnRK2.2 gene decreases drought resistance of maize. A dehydration-induced Rho-like small guanosine triphosphatase gene ZmROP8 is directly targeted and repressed by ZmAL14. Phosphorylation of ZmAL14 by ZmSnRK2.2 prevents its binding to the ZmROP8 promoter, thereby releasing the repression of ZmROP8 transcription. Overexpression of ZmROP8 stimulates peroxidase activity and reduces hydrogen peroxide accumulation after drought treatment. Collectively, our study indicates that ZmAL14 is a negative regulator of drought resistance, which can be phosphorylated by ZmSnRK2.2 through the ABA signaling pathway, thus preventing its suppression on ZmROP8 transcription during drought stress response.

Assessing the Function of CBF1 in Modulating the Interaction Between Phytochrome B and PIF4.

Phytochromes are red (R) and far-red (FR) light photoreceptors in plants. Upon light exposure, photoactivated phytochromes translocate into the nucleus, where they interact with their partner proteins to transduce light signals. The yeast two-hybrid (Y2H) system is a powerful technique for rapidly identifying and verifying protein-protein interactions, and PHYTOCHROME-INTERACTING FACTOR3 (PIF3), the founding member of the PIF proteins, was initially identified in a Y2H screen for phytochrome B (phyB)-interacting proteins. Recently, we developed a yeast three-hybrid (Y3H) system by introducing an additional vector into this Y2H system, and thus a new regulator could be co-expressed and its role in modulating the interactions between phytochromes and their signaling partners could be examined. By employing this Y3H system, we recently showed that both MYB30 and CBF1, two negative regulators of seedlings photomorphogenesis, act to inhibit the interactions between phyB and PIF4/PIF5. In this chapter, we will use the CBF1-phyB-PIF4 module as an example and describe the detailed procedure for performing this Y3H assay. It will be intriguing and exciting to explore the potential usage of this Y3H system in future research.

Pharmacokinetics of Nitazoxanide Dry Suspensions After Single Oral Doses in Healthy Subjects: Food Effects Evaluation and Bioequivalence Study.

Nitazoxanide (NTZ) is an effective antiparasitic drug with potent antiviral and antimicrobial activity. This randomized, open-label, 2-sequence, 2-period crossover trial was designed to evaluate the bioequivalence (BE) of the NTZ dry suspension in healthy subjects and investigated the effect of food intake on the pharmacokinetic (PK) properties of tizoxanide (an active metabolite of NTZ, TIZ). Sixty healthy Chinese subjects were enrolled and received a single dose of 500 mg/25 mL of preparations on days 1 and 4 under overnight fasting or fed conditions, respectively. The plasma concentration of TIZ was determined using high-performance liquid chromatography/tandem mass spectrometry. PK parameters were calculated using WinNonlin 8.2 and BE was evaluated using SAS 9.4. The 90% confidence intervals for the geometric mean ratio (test/reference) of maximum concentration (Cmax), the area under the curve from time 0 to the time of the last quantifiable concentration (AUC0-t), and the area under the curve from time 0 to extrapolation to infinity (AUC0-∞) were all within the equivalent interval of 80%-125%, compliant with BE requirements. In comparison with fasting, on taking the reference and test preparations of the NTZ dry suspension after a meal, the AUC0-t increased by 48.9% and 47.3%, respectively, the AUC0-∞ increased by 48.4% and 48.3%, respectively, and the post-meal Tmax was prolonged by 1.8-2 hours. Our results demonstrate that the test and reference preparations were bioequivalent. High-fat meals significantly improve the degree of drug absorption and delay the rate of drug absorption.

Copine proteins are required for brassinosteroid signaling in maize and Arabidopsis.

Copine proteins are highly conserved and ubiquitously found in eukaryotes, and their indispensable roles in different species were proposed. However, their exact function remains unclear. The phytohormone brassinosteroids (BRs) play vital roles in plant growth, development and environmental responses. A key event in effective BR signaling is the formation of functional BRI1-SERK receptor complex and subsequent transphosphorylation upon ligand binding. Here, we demonstrate that BONZAI (BON) proteins, which are plasma membrane-associated copine proteins, are critical components of BR signaling in both the monocot maize and the dicot Arabidopsis. Biochemical and molecular analyses reveal that BON proteins directly interact with SERK kinases, thereby ensuring effective BRI1-SERK interaction and transphosphorylation. This study advances the knowledge on BR signaling and provides an important target for optimizing valuable agronomic traits, it also opens a way to study steroid hormone signaling and copine proteins of eukaryotes in a broader perspective.

Nurses' perspectives on workplace environment needs associated to resilience: a qualitative descriptive study.

Objective: The purpose of this study was to explore the demands of nurses on the workplace environment related to psychological resilience. Methods: A qualitative descriptive design was employed for this study. Purposeful sampling was chosen from a tertiary hospital in Henan Province, China. Semi-structured in-depth interviews were conducted with 20 nurses. The interview data was analyzed using the Colaizzi's method and results were reported following the COREQ standards. Results: Analysis of the interview data revealed three main themes: (1) Career Support and Development, (2) Practical Support & Development, and (3) Personal Support and Development. Conclusion: The perspectives of nurses for a workplace environment demands needs to be appreciated, and in addition, it is worth noting that the key role of building a good workplace environment in strengthening the resilience of nurses emphasizes the need for careful consideration. Nursing administrators should formulate policies and measures from multiple perspectives based on the real needs of nurses in terms of professional, practical, and personal dimensions.

Protective Effects of Astaxanthin on Ochratoxin A-Induced Liver Injury: Effects of Endoplasmic Reticulum Stress and Mitochondrial Fission-Fusion Balance.

Ochratoxin A (OTA), a common mycotoxin, can contaminate food and feed and is difficult to remove. Astaxanthin (ASTA), a natural antioxidant, can effectively protect against OTA-induced hepatotoxicity; however, its mechanism of action remains unclear. In the present study, we elucidate the protective effects of ASTA on the OTA-induced damage of the endoplasmic reticulum and mitochondria in broiler liver samples by serum biochemical analysis, antioxidant analysis, qRT-PCR, and Western blot analysis. ASTA inhibited the expressions of ahr, pxr, car, cyp1a1, cyp1a5, cyp2c18, cyp2d6, and cyp3a9 genes, and significantly alleviated OTA-induced liver oxidative damage (SOD, GSH-Px, GSH, MDA). Furthermore, it inhibited OTA-activated endoplasmic reticulum stress genes and proteins (grp94, GRP78, atf4, ATF6, perk, eif2α, ire1, CHOP). ASTA alleviated OTA-induced mitochondrial dynamic imbalance, inhibited mitochondrial division (DRP1, mff), and promoted mitochondrial fusion (OPA1, MFN1, MFN2). In conclusion, ASTA can decrease OTA-induced oxidative damage, thereby alleviating endoplasmic reticulum stress and mitochondrial dynamic imbalance.

Bacillus velezensis A2 Can Protect against Damage to IPEC-J2 Cells Induced by Zearalenone via the Wnt/FRZB/ß-Catenin Signaling Pathway.

Zearalenone (ZEA) has adverse effects on human and animal health, and finding effective strategies to combat its toxicity is essential. The probiotic Bacillus velezensis A2 shows various beneficial physiological functions, including the potential to combat fungal toxins. However, the detailed mechanism by which the Bacillus velezensis A2 strain achieves this protective effect is not yet fully revealed. This experiment was based on transcriptome data to study the protective mechanism of Bacillus velezensis A2 against ZEA-induced damage to IPEC-J2 cells. The experiment was divided into CON, A2, ZEA, and A2+ZEA groups. This research used an oxidation kit to measure oxidative damage indicators, the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) method to detect cell apoptosis, flow cytometry to determine the cell cycle, and transcriptome sequencing to screen and identify differentially expressed genes. In addition, gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were adopted to screen out relevant signaling pathways. Finally, to determine whether A2 can alleviate the damage caused by ZEA to cells, the genes and proteins involved in inflammation, cell apoptosis, cell cycles, and related pathways were validated using a quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot methods. Compared with the CON group, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in the ZEA group increased significantly (p < 0.01), while the levels of antioxidant enzyme activity, total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-PX), total antioxidant capacity (T-AOC), and catalase (CAT) decreased significantly (p < 0.01). Compared with the ZEA group, the A2+ZEA group showed a significant decrease in ROS and MDA levels (p < 0.01), while the levels of T-SOD, GSH-PX, T-AOC, and CAT increased significantly (p < 0.01). TUNEL and cell cycle results indicated that compared with the ZEA group, the A2+ZEA group demonstrated a significant decrease in the cell apoptosis rate (p < 0.01), and the cell cycle was restored. Combining transcriptome data, qRT-PCR, and Western blot, the results showed that compared with the CON group, the mRNA and protein expression levels of Wnt10 and ß-catenin increased significantly (p < 0.01), while the expression level of FRZB decreased significantly (p < 0.01); compared with the ZEA group, the expression levels of these mRNA and proteins were reversed. Bacillus velezensis A2 can increase the antioxidant level, reduce inflammatory damage, decrease cell apoptosis, and correct the cell cycle when that damage is being caused by ZEA. The protective mechanism may be related to the regulation of the Wnt/FRZB cell/ß-catenin signaling pathway.

Genetic and lipidomic analyses reveal the key role of lipid metabolism for cold tolerance in maize.

Lipid remodeling is crucial for cold tolerance in plants. However, the precise alternations of lipidomics during cold responses remain elusive, especially in maize (Zea mays L.). In addition, the key genes responsible for cold tolerance in maize lipid metabolism have not been identified. Here, we integrate lipidomic, transcriptomic, and genetic analysis to determine the profile of lipid remodeling caused by cold stress. We find that the homeostasis of cellular lipid metabolism is essential for maintaining cold tolerance of maize. Also, we detect 210 lipid species belonging to 13 major classes, covering phospholipids, glycerides, glycolipids, and free fatty acids. Various lipid metabolites undergo specific and selective alterations in response to cold stress, especially mono-/di-unsaturated lysophosphatidic acid, lysophosphatidylcholine, phosphatidylcholine, and phosphatidylinositol, as well as polyunsaturated phosphatidic acid, monogalactosyldiacylglycerol, diacylglycerol, and triacylglycerol. In addition, we identify a subset of key enzymes, including ketoacyl-acyl-carrier protein synthase II (KAS II), acyl-carrier protein 2 (ACP2), male sterility33 (Ms33), and stearoyl-acyl-carrier protein desaturase 2 (SAD2) involved in glycerolipid biosynthetic pathways are positive regulators of maize cold tolerance. These results reveal a comprehensive lipidomic profile during the cold response of maize and provide genetic resources for enhancing cold tolerance in crops.

Prevalence and related factors of cognitive frailty in diabetic patients in China: a systematic review and meta-analysis.

Objective: Cognitive frailty (CF) is characterized by physical frailty and potentially reversible cognitive impairment without Alzheimer's disease and other dementias. Clarifying the prevalence and related factors of cognitive frailty can help researchers understand its epidemiological status and formulate intervention measures. This study aims to conduct a systematic review and meta-analysis of the prevalence and related factors of CF in diabetic patients in Chinas to better understand the current status of CF in diabetic patients in China and develop effective intervention measures for related factors. Methods: PubMed, Web of Science, Embase, Cochrane Library, CNKI, Weipu(VIP), WANFANG, China Biology Medicine (CBM) and DUXIU were searched to collect epidemiological data on Chinese diabetic patients. Articles published through May 29, 2023, were searched. The number of diabetes with CF and the total number of diabetes in the included studies were extracted to estimate the prevalence of diabetes with CF. For factors related to diabetes with CF, odds ratios (OR) and 95% confidence intervals (CI) were used for estimation. Results: A total of 248 records were screened, of which 18 met the inclusion criteria. The results of meta-analysis showed that the prevalence of Chinese diabetic patients with CF was 25.8% (95% CI = 19.7 to 31.9%). Subgroup analysis showed that hospital prevalence was higher than in the community and in women than in men. Combined estimates showed that depression, malnutrition, advanced age (≥70, ≥80), combined chronic diseases ≥4 and glycated hemoglobin ≥8.5 were risk factors for CF in diabetics patients in China, with regular exercise and high education level (≥ college) as protective factors. Conclusion: Cognitive frailty was common in diabetic patients in China. Such populations should be screened early and intervened with relevant factors.Systematic review registration: A systematic review of this study evaluated the registered websites as https://www.crd.york.ac.uk/PROSPERO/, CRD42023431396.

Electrospun VO2/carbon fibers for aqueous zinc-ion batteries.

Aqueous zinc-ion batteries (AZIBs) have become one of the most potential energy storage devices due to their high safety and low cost. Vanadium oxide is an ideal cathode material for AZIBs because of its unique tunnel structure and multivalent nature. In this work, electrospun VO2/carbon fibers (VO2@CPAN) with a three-dimensional (3D) network are obtained by an electrospinning strategy combining with a controlled heat treatment. As cathode for AZIBs, the 3D network of the carbon fiber significantly improves the conductivity of VO2, avoids the agglomeration of VO2, and increases the stability of VO2. Therefore, VO2@CPAN delivers a specific capacity of 323.2 mA h g-1 at 0.2 A g-1, which is higher than pure VO2. At the same time, excellent capacity retention of 76.6% is obtained at high current density of 10 A g-1 after 3000 cycles.

Dairy consumption in adults in China: a systematic review.

BACKGROUND: Research on dairy consumption in China is lacking, however, some evidence has demonstrated significant changes in recent years, with a reported increase in the overall consumption of dairy products. To fully understand these changes, a systematic review was conducted to examine reported dairy intakes and differences between dairy consumption in different population groups in China. METHODS: Web of Science, Embase, and PubMed databases were searched for studies published from January 2000 to September 2022. The China National Knowledge Infrastructure (CNKI) was used to retrieve papers available in Chinese. Papers reporting dietary intakes of dairy consumption across age, sex, and geographical location sub-groups were considered for inclusion in this review. In addition, this review includes the consumption of different types of dairy foods and changes in dairy intake over time. RESULTS: Forty-seven papers were included in the present study. Twelve papers examined dairy consumption across age groups, showing that middle-aged adults tend to consume less dairy than other age groups. Studies comparing across location-specific cohorts reported dairy intakes among urban populations were higher than rural, as well as being higher than the national average. Coastal, Northern and Eastern residents consumed more dairy products than those living in other regions of China, and people in larger cities had higher reported intakes than smaller cities. Milk was the primary dairy product reportedly consumed by Chinese population, followed by yogurt. Concerning sex, evidence showed that females generally reported a greater daily dairy intake than males. CONCLUSIONS: This review shows that, in China, several different population groups displayed significant differences in the amount and type of dairy consumed. When considering the incorporation of dairy products into healthy eating guidelines or positioning specific dairy products on the market, it is important to consider the differences and variations in consumption patterns within population groups.

W-doped VO2 for high-performance aqueous Zn-ion batteries.

Aqueous Zn-ion batteries (AZIBs) have become one of the most promising energy storage devices due to their high safety and low cost. However, the development of stable cathodes with fast kinetics and high energy density is the key to achieving large-scale application of AZIBs. In this work, W-doped VO2 (W-VO2) is developed by a one-step hydrothermal method. Benefiting from the pre-insertion of W6+ and the introduction of the W-O bond, accomplishing an expanded lattice spacing and a stable structure, both improved kinetics and long cycle life are achieved. The W-VO2 delivers a specific capacity of 340.2 mA h g-1 at 0.2 A g-1, an excellent high-rate capability with a discharge capacity of 186.9 mA h g-1 at 10 A g-1, and long-term cycling stability with a capacity retention of 76.5% after 2000 cycles. The electrochemical performance of the W-VO2 has been greatly improved, compared with the pure VO2. The W doping strategy proposed here also presents an encouraging pathway for developing other high-energy and stable cathodes.

Determining patients with spinal metastases suitable for surgical intervention: A cost-effective analysis.

BACKGROUND: Both nonoperative and operative treatments for spinal metastasis are expensive interventions. Patients' expected 3-month survival is believed to be a key factor to determine the most suitable treatment. However, to the best of our knowledge, no previous study lends support to the hypothesis. We sought to determine the cost-effectiveness of operative and nonoperative interventions, stratified by patients' predicted probability of 3-month survival. METHODS: A Markov model with four defined health states was used to estimate the quality-adjusted life years (QALYs) and costs for operative intervention with postoperative radiotherapy and radiotherapy alone (palliative low-dose external beam radiotherapy) of spine metastases. Transition probabilities for the model, including the risks of mortality and functional deterioration, were obtained from secondary and our institutional data. Willingness to pay thresholds were prespecified at $100,000 and $150,000. The analyses were censored after 5-year simulation from a health system perspective and discounted outcomes at 3% per year. Sensitivity analyses were conducted to test the robustness of the study design. RESULTS: The incremental cost-effectiveness ratios were $140,907 per QALY for patients with a 3-month survival probability >50%, $3,178,510 per QALY for patients with a 3-month survival probability <50%, and $168,385 per QALY for patients with independent ambulatory and 3-month survival probability >50%. CONCLUSIONS: This study emphasizes the need to choose patients carefully and estimate preoperative survival for those with spinal metastases. In addition to reaffirming previous research regarding the influence of ambulatory status on cost-effectiveness, our study goes a step further by highlighting that operative intervention with postoperative radiotherapy could be more cost-effective than radiotherapy alone for patients with a better survival outlook. Accurate survival prediction tools and larger future studies could offer more detailed insights for clinical decisions.

The Critical Role of The Piezo1/ß-catenin/ATF4 Axis on The Stemness of Gli1+ BMSCs During Simulated Microgravity-Induced Bone Loss.

Disuse osteoporosis is characterized by decreased bone mass caused by abnormal mechanical stimulation of bone. Piezo1 is a major mechanosensitive ion channel in bone homeostasis. However, whether intervening in the action of Piezo1 can rescue disuse osteoporosis remains unresolved. In this study, a commonly-used hindlimb-unloading model is employed to simulate microgravity. By single-cell RNA sequencing, bone marrow-derived mesenchymal stem cells (BMSCs) are the most downregulated cell cluster, and coincidentally, Piezo1 expression is mostly enriched in those cells, and is substantially downregulated by unloading. Importantly, activation of Piezo1 by systemically-introducing yoda1 mimics the effects of mechanical stimulation and thus ameliorates bone loss under simulated microgravity. Mechanistically, Piezo1 activation promotes the proliferation and osteogenic differentiation of Gli1+ BMSCs by activating the ß-catenin and its target gene activating transcription factor 4 (ATF4). Inhibiting ß-catenin expression substantially attenuates the effect of yoda1 on bone loss, possibly due to inhibited proliferation and osteogenic differentiation capability of Gli1+ BMSCs mediated by ATF4. Lastly, Piezo1 activation also slightly alleviates the osteoporosis of OVX and aged mice. In conclusion, impaired function of Piezo1 in BMSCs leads to insufficient bone formation especially caused by abnormal mechanical stimuli, and is thus a potential therapeutic target for osteoporosis.

Strigolactones promote plant freezing tolerance by releasing the WRKY41-mediated inhibition of CBF/DREB1 expression.

Cold stress is a major abiotic stress that adversely affects plant growth and crop productivity. The C-REPEAT BINDING FACTOR/DRE BINDING FACTOR 1 (CBF/DREB1) transcriptional regulatory cascade plays a key role in regulating cold acclimation and freezing tolerance in Arabidopsis (Arabidopsis thaliana). Here, we show that max (more axillary growth) mutants deficient in strigolactone biosynthesis and signaling display hypersensitivity to freezing stress. Exogenous application of GR245DS , a strigolactone analog, enhances freezing tolerance in wild-type plants and strigolactone-deficient mutants and promotes the cold-induced expression of CBF genes. Biochemical analysis showed that the transcription factor WRKY41 serves as a substrate for the F-box E3 ligase MAX2. WRKY41 directly binds to the W-box in the promoters of CBF genes and represses their expression, negatively regulating cold acclimation and freezing tolerance. MAX2 ubiquitinates WRKY41, thus marking it for cold-induced degradation and thereby alleviating the repression of CBF expression. In addition, SL-mediated degradation of SMXLs also contributes to enhanced plant freezing tolerance by promoting anthocyanin biosynthesis. Taken together, our study reveals the molecular mechanism underlying strigolactones promote the cold stress response in Arabidopsis.

Genetic and molecular exploration of maize environmental stress resilience: Toward sustainable agriculture.

Global climate change exacerbates the effects of environmental stressors, such as drought, flooding, extreme temperatures, salinity, and alkalinity, on crop growth and grain yield, threatening the sustainability of the food supply. Maize (Zea mays) is one of the most widely cultivated crops and the most abundant grain crop in production worldwide. However, the stability of maize yield is highly dependent on environmental conditions. Recently, great progress has been made in understanding the molecular mechanisms underlying maize responses to environmental stresses and in developing stress-resilient varieties due to advances in high-throughput sequencing technologies, multi-omics analysis platforms, and automated phenotyping facilities. In this review, we summarize recent advances in dissecting the genetic factors and networks that contribute to maize abiotic stress tolerance through diverse strategies. We also discuss future challenges and opportunities for the development of climate-resilient maize varieties.