Grain size is an important component trait of grain yield, which is frequently threatened by abiotic stress. However, little is known about how grain yield and abiotic stress tolerance are regulated. ...Here, we characterize GSA1, a quantitative trait locus (QTL) regulating grain size and abiotic stress tolerance associated with metabolic flux redirection. GSA1 encodes a UDP-glucosyltransferase, which exhibits glucosyltransferase activity toward flavonoids and monolignols. GSA1 regulates grain size by modulating cell proliferation and expansion, which are regulated by flavonoid-mediated auxin levels and related gene expression. GSA1 is required for the redirection of metabolic flux from lignin biosynthesis to flavonoid biosynthesis under abiotic stress and the accumulation of flavonoid glycosides, which protect rice against abiotic stress. GSA1 overexpression results in larger grains and enhanced abiotic stress tolerance. Our findings provide insights into the regulation of grain size and abiotic stress tolerance associated with metabolic flux redirection and a potential means to improve crops.
Recurrence rates of diabetic foot ulcers vary widely in the published literature. The aim of this systematic review is to estimate recurrence rates of diabetic foot ulcers. We did a PubMed search and ...performed a review of reference lists for studies reporting recurrence of diabetic foot ulcers. The weighted relative risk (RR) and corresponding 95% confidence interval (CI) for recurrence was estimated. Forty‐nine studies reporting recurrence of diabetic foot ulcers were included. A pooled estimate for recurrence rate was 22.1% per person‐year (py) (95% CI, 19.0‐25.2%). Recurrence rate was 24.9% per py in Europe (95% CI, 20.0%‐29.7%), 17.8% per py in North America (95% CI, 12.7%‐22.9%), 16.9% per py in Africa (95% CI, 4.7%‐29.0%), and 17.0% per py in Asia (95% CI, 11.1%‐23.0%). Turkey had the highest recurrence rate of 44.4% per py (95% CI, 24.9%‐63.9%), and Bangladesh had the lowest of 4.3% per py (95% CI, 2.3%‐6.3%). Recurrence rates of diabetic foot ulcers before 2002, between 2002 and 2008, and after 2008 were 22.2% per py (95% CI, 17.6%‐26.8%), 21.9% per py (95% CI, 17.0%‐26.8%), and 21.8% per py (95% CI, 16.3%‐27.2%), respectively. Recurrence rates of diabetic foot ulcers are high. Recurrence rates vary widely in different regions and have decreased recently. More attention towards recurrence of diabetic foot ulcers is urgently required.
Increased crop yields are required to support rapid population growth worldwide. Grain weight is a key compo- nent of rice yield, but the underlying molecular mechanisms that control it remain ...elusive. Here, we report the clon- ing and characterization of a new quantitative trait locus （QTL） for the control of rice grain length, weight and yield. This locus, GL3.1, encodes a protein phosphatase kelch （PPKL） family -- Ser/Thr phosphatase. GL3.1 is a member of the large grain WY3 variety, which is associated with weaker dephosphorylation activity than the small grain FAZ1 variety. GL3.I-WY3 influences protein phosphorylation in the spikelet to accelerate cell division, thereby re- suiting in longer grains and higher yields. Further studies have shown that GL3.1 directly dephosphorylates its sub- strate, Cyclin-TI;3, which has only been rarely studied in plants. The downregulation of Cyclin-T1;3 in rice resulted in a shorter grain, which indicates a novel function for Cyclin-T in cell cycle regulation. Our findings suggest a new mechanism for the regulation of grain size and yield that is driven through a novel phosphatase-mediated process that affects the phosphorylation of Cyclin-T1;3 during cell cycle progression, and thus provide new insight into the mechanisms underlying crop seed development. We bred a new variety containing the natural GL3.1 allele that demonstrated increased grain yield, which indicates that GL3.1 is a powerful tool for breeding high-yield crops.
Sorafenib is one a first‐line therapeutic drugs for advanced hepatocellular carcinoma (HCC). However, only 30% of patients benefit from sorafenib due to drug resistance. We and other groups have ...revealed that nuclear factor I B (NFIB) regulates liver regeneration and carcinogenesis, but its role in drug resistance is poorly known. We found that NFIB was more upregulated in sorafenib‐resistant SMMC‐7721 cells compared to parental cells. NFIB knockdown not only sensitized drug‐resistant cells to sorafenib but also inhibited the proliferation and invasion of these cells. Meanwhile, NFIB promoted the proliferation and invasion of HCC cells in vitro and facilitated tumor growth and metastasis in vivo. Knocking down NFIB synergetically inhibited tumor growth with sorafenib. Mechanically, gene expression profiling and subsequent verification experiments proved that NFIB could bind with the promoter region of a complex I inhibitor NDUFA4L2 and promote its transcription. Transcriptional upregulation of NDUFA4L2 by NFIB could thus inhibit the sorafenib‐induced reactive oxygen species accumulation. Finally, we found that NFIB was highly expressed in HCC tissues, and high NFIB expression level was associated with macrovascular invasion, advanced tumor stage, and poor prognosis of HCC patients (n = 156). In summary, we demonstrated that NFIB could transcriptionally upregulate NDUFA4L2 to enhance both intrinsic and acquired sorafenib resistance of HCC cells by reducing reactive oxygen species induction.
NFIB could directly promote transcription of NDUFA4L2 to reduce sorafenib‐induced ROS accumulation. High NFIB expression was associated with poor prognosis of HCC patients.
How the plasma membrane senses external heat-stress signals to communicate with chloroplasts to orchestrate thermotolerance remains elusive. We identified a quantitative trait locus,
Thermo-tolerance ...3
(
TT3
), consisting of two genes,
TT3.1
and
TT3.2
, that interact together to enhance rice thermotolerance and reduce grain-yield losses caused by heat stress. Upon heat stress, plasma membrane–localized E3 ligase TT3.1 translocates to the endosomes, on which TT3.1 ubiquitinates chloroplast precursor protein TT3.2 for vacuolar degradation, implying that TT3.1 might serve as a potential thermosensor. Lesser accumulated, mature TT3.2 proteins in chloroplasts are essential for protecting thylakoids from heat stress. Our findings not only reveal a
TT3.1-TT3.2
genetic module at one locus that transduces heat signals from plasma membrane to chloroplasts but also provide the strategy for breeding highly thermotolerant crops.
Heat tolerance in rice
Too much heat can damage a plant’s chloroplasts, driving yield down when temperatures exceed a crop’s normal tolerance. Zhang
et al
. identified a locus with two genes that together enhance rice thermotolerance. The ubiquitin ligase activity of Thermo-tolerance 3.1 (TT3.1) drove degradation of TT3.2, a chloroplast precursor protein that can trigger chloroplast damage in the context of heat stress. Together, these protein products respond to heat and control the damage. —PJH
A tag team of protein degradation protects rice plants from excess heat.
The output of an RLK-MAPK signaling pathway maintains cytokinin homeostasis, thereby determining spikelet number per panicle in rice.
Abstract
Grain number is a flexible trait that strongly ...contributes to grain yield. In rice (Oryza sativa), the OsMKKK10-OsMKK4-OsMPK6 cascade, which is negatively regulated by the dual-specificity phosphatase GSN1, coordinates the trade-off between grain number and grain size. However, the specific components upstream and downstream of the GSN1-MAPK module that regulate spikelet number per panicle remain obscure. Here, we report that ERECTA1 (OsER1), a negative regulator of spikelet number per panicle, acts upstream of the OsMKKK10-OsMKK4-OsMPK6 cascade and that the OsER1-OsMKKK10-OsMKK4-OsMPK6 pathway is required to maintain cytokinin homeostasis. OsMPK6 directly interacts with and phosphorylates the zinc finger transcription factor DST to enhance its transcriptional activation of CYTOKININ OXIDASE2 (OsCKX2), indicating that the OsER1-OsMKKK10-OsMKK4-OsMPK6 pathway shapes panicle morphology by regulating cytokinin metabolism. Furthermore, overexpression of either DST or OsCKX2 rescued the spikelet number phenotype of the oser1, osmkkk10, osmkk4, and osmpk6 mutants, suggesting that the DST-OsCKX2 module genetically functions downstream of the OsER1-OsMKKK10-OsMKK4-OsMPK6 pathway. These findings reveal specific crosstalk between a MAPK signaling pathway and cytokinin metabolism, shedding light on how developmental signals modulate phytohormone homeostasis to shape the inflorescence.
Perovskite solar cells have recently drawn significant attention for photovoltaic applications with a certified power conversion efficiency of more than 22%. Unfortunately, the toxicity of the ...dissolvable lead content in these materials presents a critical concern for future commercial development. This review outlines some criteria for the possible replacement of lead by less toxic elements, and highlights current research progress in the application of low-lead halide perovskites as optically active materials in solar cells. These criteria are discussed with the aim of developing a better understanding of the physio-chemical properties of perovskites and of realizing similar photovoltaic performance in perovskite materials either with or without lead. Some open questions and future development prospects are outlined for further advancing perovskite solar cells toward both low toxicity and high efficiency.
This study investigated the characteristics and mechanisms of eravacycline resistance and heteroresistance in clinical Klebsiella pneumoniae isolates. A total of 393 clinical K. pneumoniae isolates ...were collected and subjected to eravacycline and tigecycline MIC determinations using the agar dilution method. Eravacycline heteroresistance was assessed by a population analysis profile (PAP). The expression levels of efflux pumps and their regulators were determined by quantitative reverse-transcription PCR (qRT-PCR). This study identified 67 eravacycline-nonsusceptible isolates; among the extended-spectrum β-lactamase (ESBL)-positive isolates, eravacycline-nonsusceptible isolates were detected more frequently than tigecycline-nonsusceptible isolates (21.7% vs. 9.4%, p = 0.001). The study sample was observed to include 20 K. pneumoniae isolates with eravacycline heteroresistance. Compared to the reference strain, oqxA or oqxB overexpression was observed in nine eravacycline-nonsusceptible isolates (range, 35.64-309.02-fold) and 13 eravacycline-heteroresistant isolates (8.42-296.34-fold). The overexpression of macA or macB was detected in 12 eravacycline-heteroresistant isolates (3.23-28.35-fold). Overexpression of the efflux pump regulator gene ramA was observed in 11 eravacycline-nonsusceptible isolates (3.33-94.05-fold) and 18 eravacycline-heteroresistant isolates (3.89-571.70-fold). The eravacycline MICs were increased by one-fourfold by overexpression of oqxAB or macAB in three eravacycline-sensitive isolates. In conclusion, the overexpression of OqxAB and MacAB efflux pumps and the transcriptional regulator RamA were suggested to be involved in K. pneumoniae eravacycline resistance and heteroresistance.
Although the SARS-CoV-2 Omicron variant is considered to induce less severe disease, there have been no consistent results on the extent of the decrease in severity.
To compare the clinical outcomes ...of COVID-19–positive patients with Omicron and Delta variant infection.
Searches were implemented up to 8 November 2022 in PubMed, Web of Science, BioRvix, and MedRvix.
Eligible studies were cohort studies reporting the clinical outcomes of COVID-19–positive patients with Omicron and Delta variant infection, including hospitalization, intensive care unit (ICU) admission, receiving invasive mechanical ventilation (IMV), and death.
COVID-19–positive patients with Omicron and Delta variant infection.
Risk of bias was assessed employing the Newcastle-Ottawa Scale.
Random-effect models were employed to pool the ORs and 95% CIs to compare the risk of clinical outcome. I2 was employed to evaluate the heterogeneity between studies.
A total of 33 studies with 6 037 144 COVID-19–positive patients were included in this meta-analysis. In the general population of COVID-19–positive patients, compared with Delta, Omicron variant infection resulted in a decreased risk of hospitalization (10.24% vs. 4.14%, OR = 2.91, 95% CI = 2.35–3.60), ICU admission (3.67% vs. 0.48%, OR = 3.64, 95% CI = 2.63–5.04), receiving IMV (3.93% vs. 0.34%, OR = 3.11, 95% CI = 1.76–5.50), and death (2.40% vs. 0.46%, OR = 2.97, 95% CI = 2.17–4.08). In the hospitalized patients with COVID-19, compared with Delta, Omicron variant infection resulted in a decreased risk of ICU admission (20.70% vs. 12.90%, OR = 1.63, 95% CI = 1.32–2.02), receiving IMV (10.90% vs. 5.80%, OR = 1.65, 95% CI = 1.28–2.14), and death (10.72% vs. 7.10%, OR = 1.44, 95% CI = 1.22–1.71).
Compared with Delta, the severity of Omicron variant infection decreased.
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