Soluble Periostin is a potential surveillance biomarker for early and long-term response to chemotherapy in advanced breast cancer.

BACKGROUND: Noninvasive biomarkers for the assessment of response to chemotherapy in advanced breast cancer (BCa) are essential for optimized therapeutic decision-making. We evaluated the potential of soluble Periostin (POSTN) in circulation as a novel biomarker for chemotherapy efficacy monitoring. METHODS: Two hundred and thirty-one patients with different stages of BCa were included. Of those patients, 58 patients with inoperable metastatic disease receiving HER2-targeted or non-targeted chemotherapy were enrolled to assess the performances of markers in recapitulating the chemotherapy efficacy assessed by imaging. POSTN, together with CA153 or CEA at different time points (C0, C2, and C4) were determined. RESULTS: POSTN levels were significantly associated with tumor volume (P < 0.0001) and TNM stages (P < 0.0001) of BCa. For early monitoring, dynamics of POSTN could recapitulate the chemotherapy efficacy among all molecular subtypes (Cohen's weighted kappa = 0.638, P < 0.0001), much better than that of carcinoembryonic antigen (CEA) and cancer antigen 153 (CA15-3). For early partial response, superior performance of POSTN was observed (Cohen's weighted kappa = 0.827, P < 0.0001) in cases with baseline levels above 17.19 ng/mL. For long-term monitoring, the POSTN response was observed to be strongly consistent with the course of the disease. Moreover, progression free survival analysis showed that patients experienced a significant early decrease of POSTN tended to obtain more benefits from the treatments. CONCLUSIONS: The current study suggests that soluble POSTN is an informative serum biomarker to complement the current clinical approaches for early and long-term chemotherapy efficacy monitoring in advanced BCa.

Mitotic spindle positioning protein serves as prognostic biomarker in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) ranks among the most aggressive types of cancer globally. Currently, clinical tumor prognostic biomarkers still lack accuracy. Mitotic spindle positioning (MISP) protein connects microtubules to the actin cytoskeleton and adhesive plaques, playing a critical role in spindle positioning, orientation, and the process of cell division. MISP can regulate the malignant biological functions of pancreatic cancer and intrahepatic cholangiocarcinoma and it acts as biomarker for prognosis, but its role in CRC remains unclear. METHODS: This study has collected 37 CRC tissue samples and 37 corresponding adjacent nontumor tissue samples, and 57 additional CRC tissues samples. Clinical data were obtained from the patients with CRC. MISP mRNA and protein expression levels were analyzed in normal control and CRC tissues using the GEPIA and Human Protein Atlas website. MISP protein levels in the collected tissues were analyzed using immunohistochemistry. RESULTS: MISP mRNA and protein expression levels were significantly increased in CRC tissues compared to adjacent nontumor tissues. Higher MISP protein levels were associated with distant metastasis, recurrence, and lower survival rates. Kaplan-Meier analysis showed that high expression levels of MISP protein were associated with recurrence and death in CRC patients. In addition, a high expression level of MISP protein, lymph node metastasis, and distance metastasis were risk factors for recurrence and a poor prognosis in patients with CRC. CONCLUSION: Elevated MISP protein correlated with tumor metastasis, recurrence, and lower survival rates in patients with CRC, and thus, MISP has the potential to become a prognostic marker for CRC.

Genome sequence of the progenitor of wheat A subgenome Triticum urartu.

Triticum urartu (diploid, AA) is the progenitor of the A subgenome of tetraploid (Triticum turgidum, AABB) and hexaploid (Triticum aestivum, AABBDD) wheat1,2. Genomic studies of T. urartu have been useful for investigating the structure, function and evolution of polyploid wheat genomes. Here we report the generation of a high-quality genome sequence of T. urartu by combining bacterial artificial chromosome (BAC)-by-BAC sequencing, single molecule real-time whole-genome shotgun sequencing 3 , linked reads and optical mapping4,5. We assembled seven chromosome-scale pseudomolecules and identified protein-coding genes, and we suggest a model for the evolution of T. urartu chromosomes. Comparative analyses with genomes of other grasses showed gene loss and amplification in the numbers of transposable elements in the T. urartu genome. Population genomics analysis of 147 T. urartu accessions from across the Fertile Crescent showed clustering of three groups, with differences in altitude and biostress, such as powdery mildew disease. The T. urartu genome assembly provides a valuable resource for studying genetic variation in wheat and related grasses, and promises to facilitate the discovery of genes that could be useful for wheat improvement.

Intrathecal Drug Delivery System in Prepontine Cistern for Patients with Intractable Craniofacial Cancer Pain: A Multicenter Retrospective Study.

BACKGROUND: Patients with craniofacial cancer frequently suffer from severe pain. The traditional intrathecal, oral, or intravenous analgesics could only provide insufficient pain relief with many side effects. Thus, a more effective analgesia approach is required. This study aimed to investigate the safety and efficacy of placing the catheter of an intrathecal morphine pump in the prepontine cistern for the treatment of craniofacial cancer pain. METHODS: We performed a retrospective study of patients with primary or metastatic craniofacial cancer pain who received the catheter placement of an intrathecal morphine pump into the prepontine cistern in eleven medical centers from September 2019 to December 2023. Friedman test and pairwise signed-rank test were used to evaluate the difference in numeric rating scale (NRS) scores, the number of breakthrough pain episodes, dose of intrathecal morphine, and dose of systemic morphine equivalents (oral, patch, intravenous) from preoperative period to postoperative days 1, 7, and 30. P values were corrected for multiple comparisons using Bonferroni test. RESULTS: The study included 33 patients. The median (interquartile range [IQR]) of NRS scores at days 1, 7, and 30 postimplant were 2.0 (1.0-3.5), 2.0 (1.0-2.0), and 1.0 (1.0-2.0), respectively, which was significantly lower than that before surgery (median, 8.0; IQR, 7.0-10.0; all P < .001). Compared to baseline number/d of breakthrough pain episodes (median, 6.0; IQR, 4.5-10.0), there was a progressive decrease in the number/d of breakthrough pain episodes at day 1, day 7, and day 30 postimplant, and the median (IQR) were 1.0 (0.0-3.0), 2.0 (0.0-3.0), and 0.0 (0.0-1.2), respectively (all P < .001). Approximately 78.8% and 96.7% of patients reported pain relief >50% at days 1 and 30 postimplant, respectively. Compared with that at day 1 postimplant, the proportion of patients with a pain relief rate >75% at day 30 postimplant also increased with continued intrathecal treatment. Compared to the dose of baseline systemic morphine equivalents (median, 228 mg.d-1; IQR, 120-408 mg.d-1), the dose of systemic morphine equivalents reduced significantly from 0(0-120) mg.d-1 at day 1 postimplant (P = .001), to 0 (0-0) mg.d-1 at days 7 and 30 postimplant (both P < .001). Few patients reported perioperative adverse events, including nausea, constipation, hypotension, urinary retention, dry mouth, headache, and sedation. No severe adverse events occurred. CONCLUSIONS: Placing the catheter tip of an intrathecal morphine pump into the prepontine cistern could effectively relieve refractory craniofacial cancer pain with an extremely low total morphine dose requirement and few adverse events. This procedure could be considered in patients with severe refractory craniofacial cancer pain.

Efficacy of acellular fish skin graft in the management of chronic ulcer: a systematic review and meta-analysis.

BACKGROUND: The wounds failing to heal through a timely and orderly standard of care (SOC) treatment are considered as chronic wounds, which add significant burden to healthcare systems around the world. SOC treatment has been commonly applied for management of chronic wounds, but SOC alone may not be adequate to heal all ulcers effectively. Fish skin graft (FSG) is a xenogenic skin substitute which could be used for accelerating skin healing. The current study was performed with the view of evaluating the effectiveness of FSG as an adjuvant treatment of SOC for chronic ulcer treatment. METHODS: Two authors independently searched the following electronic databases: PubMed, Embase, and CENTRAL, using keywords including "diabetic foot ulcer," "fish skin graft," and "wound healing." Clinical studies that evaluated the clinical outcomes of FSG in treatment of chronic ulcers were included in this meta-analysis. Random- or fixed-effect modeled meta-analyses were performed according to the heterogeneity test result (i.e., I2), to analyze the clinical outcome of FSG. RESULTS: A total of 8 studies were included in qualitative synthesis and meta-analysis, with 145 patients treated by SOC and 245 patients treated by SOC plus FSG. There was no significant difference between two groups for time to healing (MD = 1.99, 95% CI: -3.70~7.67, p = 0.493). The complete healing rate was significantly higher in FSG group compared with SOC alone (OR = 3.44, 95% CI: 2.03~5.82, p < 0.001***). Mean percentage area reduction (PAR) was reported in six studies, with a range of 71.6~97.3%. However, many of these studies did not report the value of standard deviation (SD), so we could not pool the data. No significantly different ulcer recurrence rate (RR = 0.60, 95% CI: 0.07~5.27, p = 0.645) and severe adverse events (SAEs) risk (RR = 1.67, 95% CI: 0.42~6.61, p = 0.467) were found between two groups. CONCLUSIONS: The application of FSG treatment for patients with chronic ulcers that do not respond well to SOC management could significantly increase the complete healing rate compared with SOC alone, without increased recurrence rate and SAEs risk.

Conventional versus high-voltage, long-term pulse Radiofrequency of ganglion impar in perineal pain with advanced rectal cancer: a Randomized, double-blind controlled trial.

STUDY OBJECTIVE: Advanced rectal cancer is a common cause of perineal pain and research on the use of radiofrequency therapy for the treatment of this pain is limited. In the present study, we aimed to compare the effectiveness and safety of conventional radiofrequency (CRF) and high-voltage long-term pulsed radiofrequency (H-PRF) of radiofrequency therapy in the management of perineal pain in advanced rectal cancer. DESIGN: Randomized, Double-Blind Controlled Trial. SETTING: Sichuan Cancer Hospital & Institute and Yanjiang District People's Hospital in Sichuan, China. PARTICIPANTS: A total of 72 patients with advanced rectal cancer experiencing perineal pain who were accepted for radiofrequency treatment. INTERVENTIONS: Patients were assigned randomly (1:1) assigned to either the group CRF or H-PRF in a double-blind trial. MEASUREMENTS AND MAIN RESULTS: The primary focus was on assessing perineal pain using numeric rating scales (NRS) scores at various time points. Secondary outcomes included the duration of maintaining a sitting position, depression scores, sleep quality, consumption of Oral Morphine Equivalent and Pregabalin, and the incidence of perineal numbness. A total of 57 patients (28 patients in the group CRF and 29 patients in the group H-PRF) were investigated. At all observation time points postoperatively, both groups of patients exhibited significant reductions in pain, enhancements in depression, improvements in sleep quality, and increased duration of sitting compared to their baseline measurements (P<0.05). During the 3 months and 6 months follow-up period, the group CRF exhibited significant reduction in pain, improvement in depression, sleep quality, and increased the time of keeping a sitting position compared with the group H-PRF (P<0.05). The consumption of oral morphine equivalent and Pregabalin as well as the incidence of perineal numbness were not significantly different between groups (P > 0.05). CONCLUSION: Our results demonstrate that application of CRF and H-PRF in ganglion impar to reduce perineal pain and improve the quality of life of patients with advanced rectal cancer is safe and effective. However, the long-term effect of CRF is better compared with that of H-PRF. TRIAL REGISTRATION: https://www.chictr.org.cn/ (ChiCTR2200061800) on 02/07/2022. This study adheres to CONSORT guidelines.

Self-Powered Integrated Sensing System with In-Plane Micro-Supercapacitors for Wearable Electronics.

Self-powered integrated sensor with high-sensitivity physiological signals detection is indispensable for next-generation wearable electronic devices. Herein, a Ti3 C2 Tx /CNTs-based self-powered resistive sensor with solar cells and in-plane micro-supercapacitors (MSCs) is successfully realized on a flexible styrene-ethylene/butylene-styrene (SEBS) electrospinning film. The prepared Ti3 C2 Tx /CNTs@SEBS/CNTs nanofiber membranes exhibit high electrical conductivity and mechanical flexibility. The laser-assisted fabricated Ti3 C2 Tx /CNTs based-MSCs demonstrate a high areal energy density of 52.89 and 9.56 µWh cm-2 with a corresponding areal power density of 0.2 and 4 mW cm-2 . Additionally, the MSCs exhibit remarkable capacity retention of 90.62% after 10 000 cycles. Furthermore, the Ti3 C2 Tx /CNTs based-sensor exhibits real-time detection capability for human facial micro-expressions and pulse single under physiological conditions. The repeated bending/release tests indicate the long-time cycle stability of the Ti3 C2 Tx /CNTs based-sensor. Owing to the excellent sensing performance, the sensing array was also fabricated. It is believed that this work develops a route for designing a self-powered sensor system with flexible production, high performance, and human-friendly characteristics for wearable electronics.

Identification of KASP markers and candidate genes for drought tolerance in wheat using 90K SNP array genotyping of near-isogenic lines targeting a 4BS quantitative trait locus.

KEY MESSAGE: This study identified a novel SNP and developed a highly efficient KASP marker for drought tolerance in wheat by genotyping NILs targeting a major QTL for drought tolerance using an SNP array and validation with commercial varieties. Common wheat (Triticum aestivum L.) is an important winter crop worldwide and a typical allopolyploid with a large and complex genome. With global warming, the environmental volatility and incidence of drought in wheat-producing areas will increase. Molecular markers for drought tolerance are urgently needed to enhance drought tolerance breeding. Here, we genotyped four near-isogenic line (NIL) pairs targeting a major QTL qDSI.4B.1 on wheat chromosome arm 4BS for drought tolerance using the 90K SNP Illumina iSelect array and discovered a single nucleotide polymorphism (SNP) (Excalibur_c100336_106) with consistent genotype-phenotype associations among all four NIL pairs and their parents. Then, we converted the SNP into a Kompetitive Allele-Specific PCR (KASP) marker, with an accuracy of 100% for the four NIL pairs and their parents and as high as 81.8% for the 44 tested wheat lines with known phenotypes collected from Australia and China. Two genes near this SNP were suggested as candidate genes for drought tolerance in wheat after checking the Chinese Spring reference genome annotation version 1.1. One gene, TraesCS4B02G085300, encodes an F-box protein reportedly related to the ABA network, a main pathway for drought tolerance, and another gene, TraesCS4B02G085400, encodes a calcineurin-like metallophos-phoesterase transmembrane protein, which participates in Ca2+-dependent phosphorylation regulatory system. Based on this work and previous research on pre-harvest sprouting, we established a quick and efficient general SQV-based approach for KASP marker development, integrating genotyping by SNP arrays (S) using NILs targeting major QTL for a specific trait (Q) and validating them with commercial varieties (V). The identified SNP and developed KASP marker could be applied to marker-assisted selection in drought breeding, and further study of the candidate genes may improve our understanding of drought tolerance in wheat.

Synthesis of (+)-Xylogiblactones B and C through a Kinetic Resolution of the Allenoate γ-Addition: Stereochemical Establishment.

Concise syntheses of naturally occurring γ-butenolides (+)-xylogiblactones B and C have been achieved for the first time starting from commercial methyl crotonate in 5-8 steps. The synthetic course involves allenoate γ-addition to racemic aldehydes through a kinetic resolution to establish the required stereochemical framework as center and axial chirality and subsequent oxacyclization via gold catalysis to complete the (+)-xylogiblactone skeleton. Both key transformations proceed in a regio- and stereospecific manner. This outcome relies on finding an efficient synthetic method for racemic aldehydes as precursors for the kinetic resolution. Completion of the synthesis provides stereochemical clarification for (+)-xylogiblactones B and C.

Genomic regions controlling yield-related traits in spring wheat: a mini review and a case study for rainfed environments in Australia and China.

A genome-wide association study (GWAS) was performed in six environments to identify major or consistent alleles responsible for wheat yield traits in Australia and North China where rainfed farming system is adopted. A panel of 228 spring wheat varieties were genotyped by double digest restriction-site associated DNA genotyping-by-sequencing. A total of 223 significant marker-trait association (MTAs) and 46 candidate genes for large- or consistent-effect MTAs were identified. The results were compared with previous studies based on a mini-review of 23 GWAS analyses on wheat yield. A phenomenon seldom reported in previous studies was that MTAs responsible for the trait tended to cluster together at certain chromosome segments, and many candidate genes were in the form of gene clusters. Although linkage disequilibrium (LD) might contribute to the co-segregation of the regions, it also suggested that marker-assisted selection (MAS) or transgenic method targeting a single gene might not be as effective as MAS targeting a larger genomic region where all the genes or gene clusters underlying play important roles.

Effect of body mass index on surgical site wound infection, mortality, and postoperative hospital stay in subjects undergoing possibly curative surgery for colorectal cancer: A meta-analysis.

We performed a meta-analysis to evaluate the effect of body mass index on surgical site wound infection, mortality, and postoperative hospital stay in subjects undergoing possibly curative surgery for colorectal cancer. A systematic literature search up to March 2022 was performed and 2247 subjects with possibly curative surgery for colorectal cancer at the baseline of the studies; 2889 of them were obese, and 9358 were non-obese. Odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were calculated to assess the effect of body mass index on surgical site wound infection, mortality, and postoperative hospital stay in subjects undergoing possibly curative surgery for colorectal cancer using the dichotomous or contentious methods with a random or fixed-effect model. The obese subjects had a significantly higher surgical site wound infection after colorectal surgery (OR, 1.87; 95% CI, 1.62-2.15, P < .001), and higher mortality (OR, 1.58; 95% CI, 1.07-2.32, P = .02) in subjects with possibly curative surgery for colorectal cancer compared with non-obese. However, obese did not show any significant difference in postoperative hospital stay (MD, 0.81; 95% CI, -0.030 to 1.92, P = .15) compared with non-obese in subjects with possibly curative surgery for colorectal cancer. The obese subjects had a significantly higher surgical site wound infection after colorectal surgery, higher mortality, and no significant difference in postoperative hospital stay compared with non-obese in subjects with possibly curative surgery for colorectal cancer. The analysis of outcomes should be with caution because of the low number of studies in certain comparisons.

Genome-wide identification of seed storage protein gene regulators in wheat through coexpression analysis.

Only a few transcriptional regulators of seed storage protein (SSP) genes have been identified in common wheat (Triticum aestivum L.). Coexpression analysis could be an efficient approach to characterize novel transcriptional regulators at the genome-scale considering the correlated expression between transcriptional regulators and target genes. As the A genome donor of common wheat, Triticum urartu is more suitable for coexpression analysis than common wheat considering the diploid genome and single gene copy. In this work, the transcriptome dynamics in endosperm of T. urartu throughout grain filling were revealed by RNA-Seq analysis. In the coexpression analysis, a total of 71 transcription factors (TFs) from 23 families were found to be coexpressed with SSP genes. Among these TFs, TuNAC77 enhanced the transcription of SSP genes by binding to cis-elements distributed in promoters. The homolog of TuNAC77 in common wheat, TaNAC77, shared an identical function, and the total SSPs were reduced by about 24% in common wheat when TaNAC77 was knocked down. This is the first genome-wide identification of transcriptional regulators of SSP genes in wheat, and the newly characterized transcriptional regulators will undoubtedly expand our knowledge of the transcriptional regulation of SSP synthesis.

Soluble POSTN is a novel biomarker complementing CA153 and CEA for breast cancer diagnosis and metastasis prediction.

BACKGROUND: Breast cancer (BCa) is the leading cause of cancer deaths among women. Reliable biomarkers for early diagnosis and metastasis prediction are essential to improve the prognosis of BCa. This study aimed to evaluate serum periostin (POSTN) as a novel biomarker complementing CA153 (carbohydrate antigen 153) and CEA (carcinoembryonic antigen) for BCa diagnosis and metastasis prediction. METHODS: To assess the potential of soluble POSTN as a circulating biomarker, 242 participants, including 173 patients with different stages of BCa and 69 healthy individuals, were enrolled in this study. Soluble POSTN, together with CA153 and CEA, were determined in serum by enzyme linked immunosorbent assay (ELISA) or electrochemiluminescence immunoassays. RESULTS: Serum POSTN levels in locoregional BCa patients were significantly higher than that in healthy controls. Receiver operating curve (ROC) analysis revealed that, to distinguish health controls from locoregional BCa, POSTN was observed with the highest AUC (area under curve) (AUCPOSTN = 0.72 [0.65 - 0.79], AUCCA153 = 0.57 [0.49 - 0.64], AUCCEA = 0.62 [0.55 - 0.69]), and both CA153 and CEA were observed with significantly improved AUCs by combination with POSTN (AUCPOSTN + CA153 = 0.74 [0.67 - 0.80], P < 0.001; AUCPOSTN + CEA = 0.77 [0.70 - 0.82], P < 0.001). Moreover, the performances of the POSTN were comparable with that of CA153 in predicting distant metastasis of BCa (AUCPOSTN = 0.78 [0.71 - 0.84], AUCCA153 = 0.82 [0.76 - 0.88]). Kaplan-Meier analysis indicated that elevated serum POSTN was associated with poor overall survival and progression-free survival. CONCLUSIONS: This study suggested that soluble POSTN is a promising potential biomarker for diagnosis and metastasis prediction of BCa.

Mirror Clock: A Strategy for Identifying Atomic Clock Frequency Jumps.

Atomic clock frequency jumps directly influence the accuracy and reliability of timekeeping systems. The necessary corrections are typically implemented by postprocessing mutual comparison data between multiple atomic clocks based on the overly strict assumption that these atomic clocks are independent of each other. This paper describes the concept of a mirror clock, which enables atomic clock frequency jumps to be identified in real time without any assumptions. By comparing whether the real measured data and a corresponding mirror clock prediction fall within a confidence interval determined by the uncertainty of past physical clock data, atomic clock frequency jumps can be effectively identified and corrected. The results of several experiments using three hydrogen masers verify that the precision and recall of simultaneous jump identification reach 96.41% and 73.49%, respectively.

[Metabolomic changes of neonatal sepsis: an exploratory clinical study]. / æ–°ç”Ÿå„¿è´¥è¡€ç—‡çš„ä»£è°¢ç»„å­¦æ”¹å˜ï¼šä¸€é¡¹æŽ¢ç´¢æ€§ä¸´åºŠç ”ç©¶.

OBJECTIVES: To study the metabolic mechanism of neonatal sepsis at different stages by analyzing the metabolic pathways involving the serum metabolites with significant differences in neonates with sepsis at different time points after admission. METHODS: A total of 20 neonates with sepsis who were hospitalized in the Department of Neonatology, Hunan Provincial People's Hospital, from January 1, 2019 to January 1, 2020 were enrolled as the sepsis group. Venous blood samples were collected on days 1, 4, and 7 after admission. Ten healthy neonates who underwent physical examination during the same period were enrolled as the control group. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for the metabonomic analysis of serum samples to investigate the change in metabolomics in neonates with sepsis at different time points. RESULTS: On day 1 after admission, the differentially expressed serum metabolites between the sepsis and control groups were mainly involved in the biosynthesis of terpenoid skeleton. For the sepsis group, the differentially expressed serum metabolites between days 1 and 4 after admission were mainly involved in pyruvate metabolism, and those between days 4 and 7 after admission were mainly involved in the metabolism of cysteine and methionine. The differentially expressed serum metabolites between days 1 and 7 after admission were mainly involved in ascorbic acid metabolism. CONCLUSIONS: The metabolic mechanism of serum metabolites varies at different stages in neonates with sepsis and is mainly associated with terpenoid skeleton biosynthesis, pyruvate metabolism, cysteine/methionine metabolism, and ascorbic acid metabolism.

Natural variations in the promoter of Awn Length Inhibitor 1 (ALI-1) are associated with awn elongation and grain length in common wheat.

Wheat awn plays a vital role in photosynthesis, grain production, and drought tolerance. However, the systematic identification or cloning of genes controlling wheat awn development is seldom reported. Here, we conducted a genome-wide association study (GWAS) with 364 wheat accessions and identified 26 loci involved in awn length development, including previously characterized B1, B2, Hd, and several rice homologs. The dominant awn suppressor B1 was fine mapped to a 125-kb physical interval, and a C2 H2 zinc finger protein Awn Length Inhibitor 1 (ALI-1) was confirmed to be the underlying gene of the B1 locus through the functional complimentary test with native awnless allele. ALI-1 expresses predominantly in the developing spike of awnless individuals, transcriptionally suppressing downstream genes. ALI-1 reduces cytokinin content and simultaneously restrains cytokinin signal transduction, leading to a stagnation of cell proliferation and reduction of cell numbers during awn development. Polymorphisms of four single nucleotide polymorphisms (SNPs) located in ALI-1 promoter region are diagnostic for the B1/b1 genotypes, and these SNPs are associated with awn length (AL), grain length (GL) and thousand-grain weight (TGW). More importantly, ali-1 was observed to increase grain length in wheat, which is a valuable attribute of awn on grain weight, aside from photosynthesis. Therefore, ALI-1 pleiotropically regulates awn and grain development, providing an alternative for grain yield improvement and addressing future climate changes.

The MYB family transcription factor TuODORANT1 from Triticum urartu and the homolog TaODORANT1 from Triticum aestivum inhibit seed storage protein synthesis in wheat.

Seed storage proteins (SSPs) are determinants of wheat end-product quality. SSP synthesis is mainly regulated at the transcriptional level. Few transcriptional regulators of SSP synthesis have been identified in wheat and this study aims to identify novel SSP gene regulators. Here, the R2R3 MYB transcription factor TuODORANT1 from Triticum urartu was found to be preferentially expressed in the developing endosperm during grain filling. In common wheat (Triticum aestivum) overexpressing TuODORANT1, the transcription levels of all the SSP genes tested by RNA-Seq analysis were reduced by 49.71% throughout grain filling, which contributed to 13.38%-35.60% declines in the total SSP levels of mature grains. In in vitro assays, TuODORANT1 inhibited both the promoter activities and the transcription of SSP genes by 1- to 13-fold. The electrophoretic mobility shift assay (EMSA) and ChIP-qPCR analysis demonstrated that TuODORANT1 bound to the cis-elements 5'-T/CAACCA-3' and 5'-T/CAACT/AG-3' in SSP gene promoters both in vitro and in vivo. Similarly, the homolog TaODORANT1 in common wheat hindered both the promoter activities and the transcription of SSP genes by 1- to 112-fold in vitro. Knockdown of TaODORANT1 in common wheat led to 14.73%-232.78% increases in the transcription of the tested SSP genes, which contributed to 11.43%-19.35% elevation in the total SSP levels. Our data show that both TuODORANT1 and TaODORANT1 are repressors of SSP synthesis.

Wheat FRIZZY PANICLE activates VERNALIZATION1-A and HOMEOBOX4-A to regulate spike development in wheat.

Kernel number per spike determined by the spike or inflorescence development is one important agricultural trait for wheat yield that is critical for global food security. While a few important genes for wheat spike development were identified, the genetic regulatory mechanism underlying supernumerary spikelets (SSs) is still unclear. Here, we cloned the wheat FRIZZY PANICLE (WFZP) gene from one local wheat cultivar. WFZP is specifically expressed at the sites where the spikelet meristem and floral meristem are initiated, which differs from the expression patterns of its homologs FZP/BD1 in rice and maize, indicative of its functional divergence during species differentiation. Moreover, WFZP directly activates VERNALIZATION1 (VRN1) and wheat HOMEOBOX4 (TaHOX4) to regulate the initiation and development of spikelet. The haplotypes analysis showed that the favourable alleles of WFZP associated with spikelet number per spike (SNS) were preferentially selected during breeding. Our findings provide insights into the molecular and genetic mechanisms underlying wheat spike development and characterize the WFZP as elite resource for wheat molecular breeding with enhanced crop yield.

A novel NAC family transcription factor SPR suppresses seed storage protein synthesis in wheat.

The synthesis of seed storage protein (SSP) is mainly regulated at the transcriptional level. However, few transcriptional regulators of SSP synthesis have been characterized in common wheat (Triticum aestivum) owing to the complex genome. As the A genome donor of common wheat, Triticum urartu could be an elite model in wheat research considering its simple genome. Here, a novel NAC family transcription factor TuSPR from T. urartu was found preferentially expressed in developing endosperm during grain-filling stages. In common wheat transgenically overexpressing TuSPR, the content of total SSPs was reduced by c. 15.97% attributed to the transcription declines of SSP genes. Both in vitro and in vivo assays showed that TuSPR bound to the cis-element 5'-CANNTG-3' distributed in SSP gene promoters and suppressed the transcription. The homolog in common wheat TaSPR shared a conserved function with TuSPR on SSP synthesis suppression. The knock-down of TaSPR in common wheat resulted in 7.07%-20.34% increases in the total SSPs. Both TuSPR and TaSPR could be superior targets in genetic engineering to manipulate SSP content in wheat, and this work undoubtedly expands our knowledge of SSP gene regulation.

Family Integrated Care for Preterm Infants in China: A Cluster Randomized Controlled Trial.

OBJECTIVE: To explore whether family integrated care (FICare) is feasible and improves the outcomes of preterm infants in China. STUDY DESIGN: This was a multicenter prospective cluster-randomized controlled trial comparing FICare and standard care. The primary outcome was length of stay (LOS). Secondary outcomes were nosocomial infections, duration of supplemental oxygen, breastfeeding, and weight gain. Outcomes were compared using univariate and multivariable analyses adjusted for potential confounders and clustering. RESULTS: We enrolled 601 preterm infants from 11 neonatal intensive care units (FICare, n = 298; control, n = 303). The unadjusted LOS was 30.81 vs 30.26 days (mean ratio, 1.02; 95% CI, 0.85-1.22; P = .85). After adjustment, outcomes in the FICare group were improved compared with the control group, including LOS (28.26 vs 35.04 days; mean ratio, 0.81; 95% CI, 0.72-0.91), total medical expenditures (mean ratio, 0.69; 95% CI, 0.53-0.90), weight gain velocity (15.73 vs 10.30 g/day; mean difference, 5.43; 95% CI, 3.65-7.21), duration of supplemental oxygen (13.11 vs 21.42 days; mean difference, 0.71; 95% CI, 0.50-1.00), nosocomial infection rates (4.13 vs 5.84/1000 hospital days; mean ratio, 0.67; 95% CI, 0.47-0.96), antibiotic exposure (38.63 vs 57.32/100 hospital days; mean ratio, 0.67; 95% CI, 0.47-0.96), breastfeeding rates (87.25% vs 55.78%; OR, 5.42; 95% CI, 3.25-9.05), and rehospitalization rates (3.65% vs 7.48%; OR, 0.47; 95% CI, 0.28-0.77). At follow-up to 18 months, breastfeeding rates and weight were significantly (P < .05) higher over time in the FICare group. CONCLUSIONS: FICare was feasible in Chinese neonatal intensive care units and was associated with reduced hospital LOS, medical expenditures, and rates of adverse outcomes.