Defining developmental trajectories of prosensory cells in human inner ear organoids at single-cell resolution.

The inner ear sensory epithelia contain mechanosensitive hair cells and supporting cells. Both cell types arise from SOX2-expressing prosensory cells, but the mechanisms underlying the diversification of these cell lineages remain unclear. To determine the transcriptional trajectory of prosensory cells, we established a SOX2-2A-ntdTomato human embryonic stem cell line using CRISPR/Cas9, and performed single-cell RNA-sequencing analyses with SOX2-positive cells isolated from inner ear organoids at various time points between differentiation days 20 and 60. Our pseudotime analysis suggests that vestibular type II hair cells arise primarily from supporting cells, rather than bi-fated prosensory cells in organoids. Moreover, ion channel- and ion-transporter-related gene sets were enriched in supporting cells versus prosensory cells, whereas Wnt signaling-related gene sets were enriched in hair cells versus supporting cells. These findings provide valuable insights into how prosensory cells give rise to hair cells and supporting cells during human inner ear development, and may provide a clue to promote hair cell regeneration from resident supporting cells in individuals with hearing loss or balance disorders.

Cell wall invertase 3 plays critical roles in providing sugars during pollination and fertilization in cucumber.

In plants, pollen-pistil interactions during pollination and fertilization mediate pollen hydration and germination, pollen tube growth, and seed set and development. Cell wall invertases (CWINs) help provide the carbohydrates for pollen development; however, their roles in pollination and fertilization have not been well established. In cucumber (Cucumis sativus), CsCWIN3 showed the highest expression in flowers, and we further examined CsCWIN3 for functions during pollination to seed set. Both CsCWIN3 transcript and CsCWIN3 protein exhibited similar expression patterns in the sepals, petals, stamen filaments, anther tapetum, and pollen of male flowers, as well as in the stigma, style, transmitting tract, and ovule funiculus of female flowers. Notably, repression of CsCWIN3 in cucumber did not affect the formation of parthenocarpic fruit but resulted in an arrested growth of stigma integuments in female flowers and a partially delayed dehiscence of anthers with decreased pollen viability in male flowers. Consequently, the pollen tube grew poorly in the gynoecia after pollination. In addition, CsCWIN3-RNA interference plants also showed affected seed development. Considering that sugar transporters could function in cucumber fecundity, we highlight the role of CsCWIN3 and a potential close collaboration between CWIN and sugar transporters in these processes. Overall, we used molecular and physiological analyses to determine the CsCWIN3-mediated metabolism during pollen formation, pollen tube growth, and plant fecundity. CsCWIN3 has essential roles from pollination and fertilization to seed set but not parthenocarpic fruit development in cucumber.

Oxidative stress in hair follicle development and hair growth: Signalling pathways, intervening mechanisms and potential of natural antioxidants.

Hair follicle development and hair growth are regulated by multiple factors and multiple signalling pathways. The hair follicle, as an important skin appendage, is the basis for hair growth, and it has the functions of safeguarding the body, perceiving the environment and regulating body temperature. Hair growth undergoes a regular hair cycle, including anagen, catagen and telogen. A small amount of physiological shedding of hair occurs under normal conditions, always in a dynamic equilibrium. Hair loss occurs when the skin or hair follicles are stimulated by oxidative stress, inflammation or hormonal disorders that disrupt the homeostasis of the hair follicles. Numerous researches have indicated that oxidative stress is an important factor causing hair loss. Here, we summarize the signalling pathways and intervention mechanisms by which oxidative stress affects hair follicle development and hair growth, discuss existing treatments for hair loss via the antioxidant pathway and provide our own insights. In addition, we collate antioxidant natural products promoting hair growth in recent years and discuss the limitations and perspectives of current hair loss prevention and treatment.

Diabetes mellitus and Alzheimer's disease: Vacuolar adenosine triphosphatase as a potential link.

Globally, the incidence of diabetes mellitus (DM) and Alzheimer's disease (AD) is increasing year by year, causing a huge economic and social burden, and their pathogenesis and aetiology have been proven to have a certain correlation. In recent years, more and more studies have shown that vacuolar adenosine triphosphatases (v-ATPases) in eukaryotes, which are biomolecules regulating lysosomal acidification and glycolipid metabolism, play a key role in DM and AD. This article describes the role of v-ATPase in DM and AD, including its role in glycolysis, insulin secretion and insulin resistance (IR), as well as its relationship with lysosomal acidification, autophagy and ß-amyloid (Aß). In DM, v-ATPase is involved in the regulation of glucose metabolism and IR. v-ATPase is closely related to glycolysis. On the one hand, v-ATPase affects the rate of glycolysis by affecting the secretion of insulin and changing the activities of key glycolytic enzymes hexokinase (HK) and phosphofructokinase 1 (PFK-1). On the other hand, glucose is the main regulator of this enzyme, and the assembly and activity of v-ATPase depend on glucose, and glucose depletion will lead to its decomposition and inactivation. In addition, v-ATPase can also regulate free fatty acids, thereby improving IR. In AD, v-ATPase can not only improve the abnormal brain energy metabolism by affecting lysosomal acidification and autophagy but also change the deposition of Aß by affecting the production and degradation of Aß. Therefore, v-ATPase may be the bridge between DM and AD.

Amorphous K-Co-Mo-Sx Chalcogel: A Synergy of Surface Sorption and Ion-Exchange.

Chalcogel represents a unique class of meso- to macroporous nanomaterials that offer applications in energy and environmental pursuits. Here, the synthesis of an ion-exchangeable amorphous chalcogel using a nominal composition of K2 CoMo2 S10 (KCMS) at room temperature is reported. Synchrotron X-ray pair distribution function (PDF), X-ray absorption near-edge structure (XANES), and extended X-ray absorption fine structure (EXAFS) reveal a plausible local structure of KCMS gel consisting of Mo5+ 2 and Mo4+ 3 clusters in the vicinity of di/polysulfides which are covalently linked by Co2+ ions. The ionically bound K+ ions remain in the percolating pores of the Co-Mo-S covalent network. XANES of Co K-edge shows multiple electronic transitions, including quadrupole (1s→3d), shakedown (1s→4p + MLCT), and dipole allowed 1s→4p transitions. Remarkably, despite a lack of regular channels as in some crystalline solids, the amorphous KCMS gel shows ion-exchange properties with UO2 2+ ions. Additionally, it also presents surface sorption via [S∙∙∙∙UO2 2+ ] covalent interactions. Overall, this study underscores the synthesis of quaternary chalcogels incorporating alkali metals and their potential to advance separation science for cations and oxo-cationic species by integrating a synergy of surface sorption and ion-exchange.

Sleep duration and mortality among breast cancer survivors in the Western New York Exposures and Breast Cancer (WEB) Study.

PURPOSE: There is increasing evidence that sleep duration may affect breast cancer survival through effects on circadian function, influencing disease progression. However, further investigation of this association is needed. METHODS: In a population-based, prospective cohort study of women from the Western New York Exposures and Breast Cancer Study, we examined mortality outcomes with invasive breast cancer identified using the National Death Index. Cox proportion hazards ratios with 95% confidence intervals were used to estimate risk of all-cause (AC) and breast cancer-specific (BC) mortality associated with self-reported usual sleep duration with adjustment for age, race/ethnicity, years of education, body mass index (BMI), menopausal status, pack-years of smoking, tumor stage, and estrogen-receptor (ER) status. We further examined associations within strata of BMI, tumor stage, menopausal status, and ER status. RESULTS: A sample of 817 patients with breast cancer were followed for a median of 18.7 years, during which 339 deaths were reported, including 132 breast cancer-specific deaths. Those who reported shorter or longer sleep tended to have a slightly higher BMI, to be less proportionately non-Hispanic White, to report a previous history of benign breast disease, and to have consumed more alcohol during their lifetime. We found no significant associations between sleep duration and AC or BC mortality, including within stratified analyses. CONCLUSION: Sleep duration was not associated with either AC or BC mortality including within strata of BMI, tumor stage, menopausal status, or ER status.

Venlafaxine-Associated Rhabdomyolysis: A Literature Review.

PURPOSE: This systematic review aimed to investigate the clinical manifestations and characteristics of venlafaxine-associated rhabdomyolysis. METHODS: A systematic search was conducted in PubMed, Elsevier, Science Direct, Embase, Springer Link, Wiley Online Library, CNKI, and Wanfang databases from the date of database inception to January 2023. Previously reported cases of venlafaxine-associated rhabdomyolysis were identified, and relevant data from these cases were collected for descriptive statistical analysis. Cases that met the inclusion criteria were evaluated to determine the correlation between adverse reactions and venlafaxine. RESULTS: A total of 12 patients with venlafaxine-associated rhabdomyolysis were included. None of these patients had a history of muscle pain or discomfort. Of the 12 patients, 5 patients received venlafaxine at doses of ≤225 mg/d, whereas the remaining 7 patients received doses exceeding 225 mg/d. The main clinical symptoms included myalgia, muscle weakness, and renal injury. All 12 patients discontinued venlafaxine and received symptomatic care. CONCLUSIONS: Venlafaxine, used either as a monotherapy or in combination with other drugs, may be associated with rhabdomyolysis. Creatine kinase levels may normalize or significantly decrease after discontinuation of venlafaxine and symptomatic treatment.

Gasdermin D deficiency aborts myeloid calcium influx to drive granulopoiesis in lupus nephritis.

Gasdermin D (GSDMD) is emerging as an important player in autoimmune diseases, but its exact role in lupus nephritis (LN) remains controversial. Here, we identified markedly elevated GSDMD in human and mouse LN kidneys, predominantly in CD11b+ myeloid cells. Global or myeloid-conditional deletion of GSDMD was shown to exacerbate systemic autoimmunity and renal injury in lupus mice with both chronic graft-versus-host (cGVH) disease and nephrotoxic serum (NTS) nephritis. Interestingly, RNA sequencing and flow cytometry revealed that myeloid GSDMD deficiency enhanced granulopoiesis at the hematopoietic sites in LN mice, exhibiting remarkable enrichment of neutrophil-related genes, significant increases in total and immature neutrophils as well as granulocyte/macrophage progenitors (GMPs). GSDMD-deficient GMPs and all-trans-retinoic acid (ATRA)-stimulated human promyelocytes NB4 were further demonstrated to possess enhanced clonogenic and differentiation abilities compared with controls. Mechanistically, GSDMD knockdown promoted self-renewal and granulocyte differentiation by restricting calcium influx, contributing to granulopoiesis. Functionally, GSDMD deficiency led to increased pathogenic neutrophil extracellular traps (NETs) in lupus peripheral blood and bone marrow-derived neutrophils. Taken together, our data establish that GSDMD deletion accelerates LN development by promoting granulopoiesis in a calcium influx-regulated manner, unraveling its unrecognized critical role in LN pathogenesis.

Feasibility of providing web-based education to patients prior to kidney transplant evaluation.

BACKGROUND: We previously developed web-based education to be used by patients prior to kidney transplant (KTX) evaluation. The current feasibility study evaluated patients' intervention uptake and barriers, and staff experiences of the clinic-wide implementation in preparation for a definitive comparative effectiveness trial. METHODS: Web links and login instructions to view 17 educational videos designed to promote KTX access were delivered via email or text to adults referred to a single transplant center between 10/2020 and 3/2021. Patient barriers were recorded. Non-completers were allowed to view the resources in the clinic. N = 7 clinic staff were interviewed about their experiences of in-clinic delivery of the web-education. Interviews were recorded with field notes and coded using simple content analysis. Patient characteristics and 30-month KTX access were examined with Chi-square, t-tests, and log-rank tests. RESULTS: Of 210 patients, 71% completed the self-education remotely (completers), 16% attempted but did not complete remotely (attempters), and 13% declined the web link invitation (decliners). Implementation barriers included technology access and use difficulties, unstable internet connectivity, limited staff time in clinic to facilitate technology use by patients, and limited technology attentiveness by patients in clinic. In 3-group comparisons, remote decliners were older with worse estimated posttransplant survival scores, and attempters were younger, more often Medicaid insured, and lived in higher area deprivation; both were more often deemed ineligible for KTX than completers. Between-group time-to-transplantation was non-significant (p = .571). CONCLUSION: The majority of patients accessed the web-education remotely; however, more vulnerable demographic populations reported greater problems accessing web-education. In-clinic delivery was burdensome to staff and patients. Future adaptive implementation strategies are needed to allow for adequate patient education.

Rh(III)-Catalyzed C-H Allylation of Aromatic Ketoximes with Vinylaziridines.

The Rh(III)-catalyzed reaction of aromatic ketoximes with 2-vinylaziridines affords ortho-allylation products of the phenyl rings of aromatic ketoximes in moderate to excellent yields. The reaction requires 0.5 equiv of NaOAc as a base and occurs under mild conditions. The protocol exhibits ortho-monoallylation selectivity, wide scope of substrates, and good compatibility of functional groups.

Cost-effectiveness of pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent or metastatic nasopharyngeal cancer.

BACKGROUND: Programmed cell death protein 1 (PD-1) monoclonal antibody, pembrolizumab, is a promising drug for platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (NPC). We aimed to assess the cost-effectiveness of pembrolizumab compared with chemotherapy for Chinese patients in this NPC. METHODS: The cost-effectiveness of pembrolizumab versus chemotherapy was evaluated using a partitioned survival model with a 5-year boundary. Efficacy and toxicity data were derived from the KEYNOTE-122 trials. Economic indicators including life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), and lifetime cost were used. One-way analysis and probabilistic sensitivity analysis (PSA) were performed to explore the uncertainties. Additionally, various scenario analyses, including different pembrolizumab price calculations and discount rates were performed. RESULTS: Pembrolizumab or chemotherapy alone respectively yielded 2.82 QALYs (3.96 LYs) and 2.73 QALYs (3.93 LYs) with an ICER of $422,535 per QALYs ($1,232,547 per LYs). This model was primarily influenced by the price of pembrolizumab. Furthermore, PSA indicated that pembrolizumab had none probability of being cost-effective compared with chemotherapy at a willingness-to- pay (WTP) of $38223. Scenario analyses revealed that irrespective of any potential price reduction or adjustments in the discount rate, no discernible impact on the ultimate outcome was observed. CONCLUSION: Pembrolizumab was less cost-effective for patients with platinum-pretreated, recurrent or metastatic NPC compared with chemotherapy in China.

Association between lung function and risk of microvascular diseases in patients with diabetes: A prospective cohort and Mendelian randomization study.

BACKGROUND AND AIMS: To investigate causal relationships of lung function with risks microvascular diseases among participants with diabetes, type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM), respectively, in prospective and Mendelian randomization (MR) study. METHODS AND RESULTS: 14,617 participants with diabetes and without microvascular diseases at baseline from the UK Biobank were included in the prospective analysis. Of these, 13,421 had T2DM and 1196 had T1DM. The linear MR analyses were conducted in the UK Biobank with 6838 cases of microvascular diseases and 10,755 controls. Lung function measurements included forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). The study outcome was microvascular diseases, a composite outcome including chronic kidney diseases, retinopathy and peripheral neuropathy. During a median follow-up of 12.1 years, 2668 new-onset microvascular diseases were recorded. FVC (%predicted) was inversely associated with the risk of new-onset microvascular diseases in participants with diabetes (Per SD increment, adjusted HR = 0.86; 95%CI:0.83-0.89), T2DM (Per SD increment, adjusted HR = 0.86; 95%CI:0.82-0.90) and T1DM (Per SD increment, adjusted HR = 0.87; 95%CI: 0.79-0.97), respectively. Similar results were found for FEV1 (%predicted). In MR analyses, genetically predicted FVC (adjusted RR = 0.55, 95%CI:0.39-0.77) and FEV1 (adjusted RR = 0.48, 95%CI:0.28-0.83) were both inversely associated with microvascular diseases in participants with T1DM. No significant association was found in those with T2DM. Similar findings were found for each component of microvascular diseases. CONCLUSION: There was a causal inverse association between lung function and risks of microvascular diseases in participants with T1DM, but not in those with T2DM.

Utilizing rubidium chloride as an effective and stable interface modification layer for high-efficiency solar cells.

The presence of interface defects between the perovskite layer and the underlying substrate has a significant impact on the power conversion efficiency (PCE) and stability of perovskite solar cells (PSCs). S n O 2 thin films are employed in PSCs as electron transport layers to achieve high PCE. However, the significant lattice mismatch between S n O 2 and the perovskite material leads to a large number of uncoordinated defects at the interface between perovskite and substrate, resulting in recombination losses at the interface. In this study, rubidium chloride (RbCl) was introduced as the interface modification layer between the perovskite layer and the S n O 2 electron transport layer to enhance the PCE of PSCs. The research showed that the RbCl interface modification layer effectively passivated the under-coordinated defects of Sn ions and optimized the energy level alignment between the perovskite layer and the S n O 2 film. Moreover, the fabricated PSCs exhibited an open-circuit voltage of 1.11 V and a power conversion efficiency of 21.64%. Furthermore, the device maintained 80% of initial efficiency after storage for 30 days in an inert gas environment and 60% of the value after storage for 30 days in ambient air.

Association of daily sitting time and coffee consumption with the risk of all-cause and cardiovascular disease mortality among US adults.

BACKGROUND: Sedentary behavior has been demonstrated to be a modifiable factor for several chronic diseases, while coffee consumption is believed to be beneficial for health. However, the joint associations of daily sitting time and coffee consumption with mortality remains poorly understood. This study aimed to evaluate the independent and joint associations of daily sitting time and coffee intakes with mortality from all-cause and cardiovascular disease (CVD) among US adults. METHODS: An analysis of a prospective cohort from the 2007-2018 National Health and Nutrition Examination Survey of US adults (n = 10,639). Data on mortality were compiled from interview and physical examination data until December 31, 2019. Daily sitting time was self-reported. Coffee beverages were from the 24-hour diet recall interview. The main outcomes of the study were all-cause and cardiovascular disease mortality. The adjusted hazard ratios [HRs] and 95% confidence intervals [CI] were imputed by Cox proportional hazards regression. RESULTS: Among 10,639 participants in the study cohort, there were 945 deaths, 284 of whom died of CVD during the follow-up period of up to 13 years. Multivariable models showed that sitting more than 8 h/d was associated with higher risks of all-cause (HR, 1.46; 95% CI, 1.17-1.81) and CVD (HR, 1.79; 95% CI, 1.21-2.66) mortality, compared with those sitting for less than 4 h/d. People with the highest quartile of coffee consumption were observed for the reduced risks of both all-cause (HR, 0.67; 95% CI, 0.54-0.84) and CVD (HR, 0.46; 95% CI, 0.30-0.69) mortality compared with non-coffee consumers. Notably, joint analyses firstly showed that non-coffee drinkers who sat six hours or more per day were 1.58 (95% CI, 1.25-1.99) times more likely to die of all causes than coffee drinkers sitting for less than six hours per day, indicating that the association of sedentary with increased mortality was only observed among adults with no coffee consumption but not among those who had coffee intake. CONCLUSIONS: This study identified that sedentary behavior for more than 6 h/d accompanied with non-coffee consumption, were strongly associated with the increased risk of mortality from all-cause and CVD.

The precautionary principle in public health emergency regime: Ethical and legal examinations of Vietnamese and global response to COVID-19.

Responses to the COVID-19 pandemic have been widely criticized for being too delayed and indecisive. As a result, the precautionary principle has been endorsed, applauded, and proposed to guide future responses to global public health emergencies. Drawing from controversial issues in response to COVID-19, especially in Vietnam, this paper critically discusses some key ethical and legal issues of employing the precautionary principle in public health emergencies. Engaging with discussions concerning this principle, especially in environmental law where the precautionary principle first appeared as a guiding principle with objective content(s), this paper formulates the precautionary principle as 'in dubio pro salus', which is about advising, justifying and demanding states to proactively prepare for scenarios arising out of any public health emergency. It distinguishes the precautionary principle into moderate and hard versions. A moderate version largely takes a holistic approach and fulfils a series of criteria specified in this paper, while a hard version either permits restrictive measures to be deployed primarily on a hypothetic basis or expresses an instrumental mentality. The hard version should be rejected because of the ethical and legal problems it raises, including risk-risk tradeoffs, internal paradoxes, unjustified causing of fear and unreasonable presupposition. Ultimately, this paper defends the moderate version.

Transcriptional control of local auxin distribution by the CsDFB1-CsPHB module regulates floral organogenesis in cucumber.

Plant cystatins are cysteine proteinase inhibitors that play key roles in defense responses. In this work, we describe an unexpected role for the cystatin-like protein DEFORMED FLORAL BUD1 (CsDFB1) as a transcriptional regulator of local auxin distribution in cucumber (Cucumis sativus L.). CsDFB1 was strongly expressed in the floral meristems, floral primordia, and vasculature. RNA interference (RNAi)-mediated silencing of CsDFB1 led to a significantly increased number of floral organs and vascular bundles, together with a pronounced accumulation of auxin. Conversely, accompanied by a decrease of auxin, overexpression of CsDFB1 resulted in a dramatic reduction in floral organ number and an obvious defect in vascular patterning, as well as organ fusion. CsDFB1 physically interacted with the cucumber ortholog of PHABULOSA (CsPHB), an HD-ZIP III transcription factor whose transcripts exhibit the same pattern as CsDFB1 Overexpression of CsPHB increased auxin accumulation in shoot tips and induced a floral phenotype similar to that of CsDFB1-RNAi lines. Furthermore, genetic and biochemical analyses revealed that CsDFB1 impairs CsPHB-mediated transcriptional regulation of the auxin biosynthetic gene YUCCA2 and the auxin efflux carrier PIN-FORMED1, and thus plays a pivotal role in auxin distribution. In summary, we propose that the CsDFB1-CsPHB module represents a regulatory pathway for local auxin distribution that governs floral organogenesis and vascular differentiation in cucumber.

Decompression sickness followed by diabetic ketoacidosis and sepsis shock: an unusual case report.

Decompression sickness (DCS) is caused by abrupt changes in extracorporeal pressure with varying severity. Symptoms range from mild musculoskeletal pain to severe organ dysfunction and death, especially among patients with chronic underlying disease. Here, we report an unusual case of a 49-year-old man who experienced DCS after a dive to a depth of 38 meters. The patient's symptoms progressed, starting with mild physical discomfort that progressed to disturbance of consciousness on the second morning. During hospitalization, we identified that in addition to DCS, he had also developed diabetic ketoacidosis, septic shock, and rhabdomyolysis. After carefully balancing the benefits and risks, we decided to provide supportive treatment to sustain vital signs, including ventilation support, sugar-reducing therapy, fluid replacement, and anti-infection medications. We then administered delayed hyperbaric oxygen (HBO2) when his condition was stable. Ultimately, the patient recovered without any sequelae. This is the first case report of a diver suffering from DCS followed by diabetic ketoacidosis and septic shock. We have learned that when DCS and other critical illnesses are highly suspected, it is essential to assess the condition comprehensively and focus on the principal contradiction.

Variety and quantity of dietary insoluble fiber intake from different sources and risk of new-onset hypertension.

BACKGROUND: The relations of the variety and quantity of different sources of dietary insoluble fibers and hypertension remain uncertain. We aimed to investigate the associations between the variety and quantity of insoluble fibers intake from six major food sources and new-onset hypertension, using data from the China Health and Nutrition Survey (CHNS). METHODS: Twelve thousand one hundred thirty-one participants without hypertension at baseline from CHNS were included. Dietary intake was measured by three consecutive 24-h dietary recalls combined with a household food inventory. The variety score of insoluble fiber sources was defined as the number of insoluble fiber sources consumed at the appropriate level, accounting for both types and quantities of insoluble fibers. The study outcome was new-onset hypertension, defined as blood pressure ≥ 140/90 mmHg, or physician-diagnosed hypertension or receiving antihypertensive treatments during the follow-up. RESULTS: During a median follow-up of 6.1 years, 4252 participants developed hypertension. There were L-shaped associations of dietary insoluble fibers derived from vegetables, beans, tubers, and fruits with new-onset hypertension; a reversed J-shaped association of whole grain-derived insoluble fiber with new-onset hypertension; and no obvious association of refined grain-derived insoluble fiber with new-onset hypertension. Therefore, refined grain was not included in the insoluble fiber variety score calculation. More importantly, a higher insoluble fiber variety score was significantly associated with lower risks of new-onset hypertension (per score increment, hazard ratio, 0.50; 95% CI, 0.45-0.55). CONCLUSIONS: There was an inverse association between the variety of insoluble fibers with appropriate quantity from different food sources and new-onset hypertension.

A U-shaped association between dietary phosphorus intake and new-onset hypertension: a nationwide cohort study in China.

BACKGROUND: The association between dietary phosphorus intake and the risk of hypertension remains uncertain. We aimed to investigate the relation of dietary phosphorus intake with new-onset hypertension among Chinese adults. METHODS: A total of 12,177 participants who were free of hypertension at baseline from the China Health and Nutrition Survey (CHNS) were included. Dietary intake was measured by 3 consecutive 24-hour dietary recalls combined with a household food inventory. New-onset hypertension was defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg or diagnosed by a physician or under antihypertensive treatment during the follow-up. RESULTS: During a median follow-up of 6.1 years, 4,269 participants developed new-onset hypertension. Overall, the association between dietary phosphorus intake and new-onset hypertension followed a U-shape (P for nonlinearity<.001). Consistently, when dietary phosphorus intake was assessed as quintiles, compared with those in the 3rd to 4th quintiles (912.0-<1089.5 mg/d), a significantly higher risk of new-onset hypertension was found in participants in the 1st to 2nd quintiles (<912.0 mg/d: HR, 1.23; 95% CI, 1.14-1.33), and the fifth quintile (≥1089.5 mg/d: HR, 1.21; 95% CI, 1.10-1.33). CONCLUSION: There was a U-shaped association between dietary phosphorus intake and new-onset hypertension in general Chinese adults.

Disruption of the amino acid transporter CsAAP2 inhibits auxin-mediated root development in cucumber.

Amino acid transporters are the principal mediators of organic nitrogen distribution within plants and are essential for plant growth and development. Despite this importance, relatively few amino acid transporter genes have been explored and elucidated in cucumber (Cucumis sativus). Here, a total of 86 amino acid transporter genes were identified in the cucumber genome. We further identified Amino Acid Permease (AAP) subfamily members that exhibited distinct expression patterns in different tissues. We found that the CsAAP2 as a candidate gene encoding a functional amino acid transporter is highly expressed in cucumber root vascular cells. CsAAP2 knockout lines exhibited arrested development of root meristem, which then caused the delayed initiation of lateral root and the inhibition of root elongation. What is more, the shoot growth of aap2 mutants was strongly retarded due to defects in cucumber root development. Moreover, aap2 mutants exhibited higher concentrations of amino acids and lignin in roots. We found that the mutant roots had a stronger ability to acidize medium. Furthermore, in the aap2 mutants, polar auxin transport was disrupted in the root tip, leading to high auxin levels in roots. Interestingly, slightly alkaline media rescued their severely reduced root growth by stimulating auxin pathway.