Gestational diabetes mellitus is associated with distinct folate-related metabolites in early and mid-pregnancy: A prospective cohort study.

AIMS: This study aimed to evaluate the association between gestational diabetes mellitus (GDM) and circulating folate metabolites, folic acid (FA) intake, and the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genotype. MATERIALS AND METHODS: A prospective pregnancy cohort study was conducted in Beijing, China, from 2022 to 2023. Circulating folate metabolites, including red blood cell (RBC) 5-methyltetrahydrofolate (5-MTHF), 5, 10-methylene-tetrahydrofolate (5,10-CH2-THF), 5- formyltetrahydrofolate (5-CHO-THF), and unmetabolised folic acid (UMFA), and plasma homocysteine (HCY), 5-MTHF, and methylmalonic acid (MMA), were determined at 6-17 weeks and 20-26 weeks of gestation. FA intake and the MTHFR and MTRR genotype were also examined. GDM was diagnosed between 24 and 28 weeks of pregnancy by a 75-g oral glucose tolerance test (OGTT). The association between the folate status and GDM was ascertained using multivariate generalised linear models, logistic regression models, and restricted cubic spline regression, adjusting for potential confounders. RESULTS: The study included 2032 pregnant women, of whom 392 (19.29%) developed GDM. UMFA above the 75th percentile (≥P75) [adjusted OR (aOR) (95% confidence interval [CI]) = 1.36 (1.01-1.84)], UMFA ≥ P90 [aOR (95% CI) = 1.82 (1.23-2.69)], and HCY ≥ P75 [aOR (95% CI) = 1.40 (1.04-1.88)] in early pregnancy, and RBC 5-MTHF [aOR (95% CI) = 1.48 (1.10-2.00)], RBC 5,10-CH2-THF [aOR (95% CI) = 1.55 (1.15-2.10)], and plasma 5-MTHF [aOR (95% CI) = 1.36 (1.00-1.86)] in mid-pregnancy ≥ P75 are associated with GDM. Higher UMFA levels in early pregnancy show positive associations with the 1-h and 2-h glucose levels during the OGTT, and higher HCY levels are associated with increased fasting glucose levels during the OGTT. In comparison, RBC 5- MTHF and 5,10-CH2-THF, and plasma 5- MTHF in mid-pregnancy are positively associated with the 1-h glucose level (p < 0.05). The MTHFR and MTRR genotype and FA intake are not associated with GDM. CONCLUSIONS: Elevated levels of UMFA and HCY during early pregnancy, along with elevated RBC 5-MTHF and 5,10-CH2-THF and plasma 5-MTHF during mid-pregnancy, are associated with GDM. These findings indicate distinct connections between different folate metabolites and the occurrence of GDM.

Role of dynamic contrast-enhanced MRI in predicting severe acute radiation-induced rectal injury in patients with rectal cancer.

OBJECTIVES: To explore the potential of dynamic contrast-enhanced MRI (DCE-MRI) quantitative parameters in predicting severe acute radiation-induced rectal injury (RRI) in rectal cancer. METHODS: This retrospective study enrolled 49 patients with rectal cancer who underwent neoadjuvant chemoradiotherapy and rectal MRI including a DCE-MRI sequence from November 2014 to March 2021. Two radiologists independently measured DCE-MRI quantitative parameters, including the forward volume transfer constant (Ktrans), rate constant (kep), fractional extravascular extracellular space volume (ve), and the thickness of the rectal wall farthest away from the tumor. These parameters were compared between mild and severe acute RRI groups based on histopathological assessment. Receiver operating characteristic curve analysis was performed to analyze statistically significant parameters. RESULTS: Forty-nine patients (mean age, 54 years ± 12 [standard deviation]; 37 men) were enrolled, including 25 patients with severe acute RRI. Ktrans was lower in severe acute RRI group than mild acute RRI group (0.032 min-1 vs 0.054 min-1; p = 0.008), but difference of other parameters (kep, ve and rectal wall thickness) was not significant between these two groups (all p > 0.05). The area under the receiver operating characteristic curve of Ktrans was 0.72 (95% confidence interval: 0.57, 0.84). With a Ktrans cutoff value of 0.047 min-1, the sensitivity and specificity for severe acute RRI prediction were 80% and 54%, respectively. CONCLUSION: Ktrans demonstrated moderate diagnostic performance in predicting severe acute RRI. CLINICAL RELEVANCE STATEMENT: Dynamic contrast-enhanced MRI can provide non-invasive and objective evidence for perioperative management and treatment strategies in rectal cancer patients with acute radiation-induced rectal injury. KEY POINTS: • To our knowledge, this study is the first to evaluate the predictive value of contrast-enhanced MRI (DCE-MRI) quantitative parameters for severe acute radiation-induced rectal injury (RRI) in patients with rectal cancer. • Forward volume transfer constant (Ktrans), derived from DCE-MRI, exhibited moderate diagnostic performance (AUC = 0.72) in predicting severe acute RRI of rectal cancer, with a sensitivity of 80% and specificity of 54%. • DCE-MRI is a promising imaging marker for distinguishing the severity of acute RRI in patients with rectal cancer.

The influence of maternal prepregnancy weight and gestational weight gain on the umbilical cord blood metabolome: a case-control study.

BACKGROUND: Maternal overweight/obesity and excessive gestational weight gain (GWG) are frequently reported to be risk factors for obesity and other metabolic disorders in offspring. Cord blood metabolites provide information on fetal nutritional and metabolic health and could provide an early window of detection of potential health issues among newborns. The aim of the study was to explore the impact of maternal prepregnancy overweight/obesity and excessive GWG on cord blood metabolic profiles. METHODS: A case control study including 33 pairs of mothers with prepregnancy overweight/obesity and their neonates, 30 pairs of mothers with excessive GWG and their neonates, and 32 control mother-neonate pairs. Untargeted metabolomic profiling of umbilical cord blood samples were performed using UHPLC‒MS/MS. RESULTS: Forty-six metabolites exhibited a significant increase and 60 metabolites exhibited a significant reduction in umbilical cord blood from overweight and obese mothers compared with mothers with normal body weight. Steroid hormone biosynthesis and neuroactive ligand‒receptor interactions were the two top-ranking pathways enriched with these metabolites (P = 0.01 and 0.03, respectively). Compared with mothers with normal GWG, in mothers with excessive GWG, the levels of 63 metabolites were increased and those of 46 metabolites were decreased in umbilical cord blood. Biosynthesis of unsaturated fatty acids was the most altered pathway enriched with these metabolites (P < 0.01). CONCLUSIONS: Prepregnancy overweight and obesity affected the fetal steroid hormone biosynthesis pathway, while excessive GWG affected fetal fatty acid metabolism. This emphasizes the importance of preconception weight loss and maintaining an appropriate GWG, which are beneficial for the long-term metabolic health of offspring.

Cell- and noncell-autonomous AUXIN RESPONSE FACTOR3 controls meristem proliferation and phyllotactic patterns.

In cell-cell communication, noncell-autonomous transcription factors play vital roles in controlling plant stem cell fate. We previously reported that AUXIN RESPONSE FACTOR3 (ARF3), a member of the ARF family with critical roles in floral meristem maintenance and determinacy, has a distinct accumulation pattern that differs from the expression domain of its encoding gene in the shoot apical meristem (SAM). However, the biological meaning of this difference is obscure. Here, we demonstrate that ARF3 expression in Arabidopsis (Arabidopsis thaliana) is mainly activated at the periphery of the SAM by auxin where ARF3 cell autonomously regulates the expression of meristem-organ boundary-specific genes, such as CUP-SHAPED COTYLEDON1-3 (CUC1-3), BLADE ON PETIOLE1-2 (BOP1-2), and TARGETS UNDER ETTIN CONTROL3 (TEC3) to regulate the arrangement of organs in regular pattern, a phenomenon referred to as phyllotaxis. We also show that ARF3 is translocated into the organizing center where it represses cytokinin activity and WUSCHEL expression to regulate meristem activity noncell-autonomously. Therefore, ARF3 acts as a molecular link that mediates the interaction of auxin and cytokinin signaling in the SAM while coordinating the balance between meristem maintenance and organogenesis. Our findings reveal an ARF3-mediated coordination mechanism through cell-cell communication in dynamic SAM maintenance.

MRI-detected tumor deposits in cT3 and cT4 rectal cancer following neoadjuvant chemoradiotherapy.

OBJECTIVES: To evaluate the identification of tumor deposits (TDs) and the prognostic significance of an MRI tumor regression grade for TDs in patients with rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT). METHODS: Ninety-one patients with cT3 or cT4 rectal cancer who underwent surgery following nCRT between August 2014 and June 2020 were retrospectively analyzed. Changes in pre-nCRT MRI-detected TDs (mrTDs) were described as mrTD regression grade. The diagnostic performance of post-nCRT MRI-detected TDs (ymrTDs) was compared with histopathological reference standard. The correlation between ymrTDs, mrTD regression grade, and disease-free survival (DFS) was assessed. RESULTS: The sensitivity and specificity of ymrTDs were 88.00% and 89.39%, respectively. The area under the receiver operating characteristic curve was 0.887 (95% confidence interval [CI]: 0.803-0.944). The 3-year DFS of patients with positive ymrTDs was significantly lower than of the negative group (44.83% vs 82.73%, p < 0.001). The 3-year DFS was 33.33% for patients with poor regression of mrTDs following nCRT and 55.56% for those with moderate regression, compared to 69.23% in good responders and 83.97% in patients without mrTDs (p < 0.001). On multivariable Cox regression, mrTD regression grade was the only independent MRI factor associated with DFS (p = 0.042). CONCLUSIONS: Diagnostic performance of ymrTDs was moderate. The mrTD regression grade was independently correlated with DFS, which may have a prognostic implication for treatment and follow-up. CLINICAL RELEVANCE STATEMENT: Patients with poor regression of MRI-detected tumor deposits may benefit from more aggressive treatments, such as chemoradiation therapy plus induction or consolidation chemotherapy. KEY POINTS: • MRI provides a preoperative and noninvasive way to visualize tumor deposits (TDs) after neoadjuvant chemoradiotherapy (nCRT). • Post-nCRT MRI-detected TDs are a poor prognostic marker in cT3 and cT4 rectal cancer patients. • The regression of MRI-detected TDs after nCRT is associated with an improved disease-free survival.

Quantitative assessment of the microstructure of the mesorectum with different prognostic statuses by intravoxel incoherent motion diffusion-weighed magnetic resonance imaging.

BACKGROUND: The mesorectum surrounding the rectum provides an ideal substrate for tumour spread. However, preoperative risk assessment is still an issue. This study aimed to investigate the microstructural features of mesorectum with different prognostic statuses by intravoxel incoherent motion diffusion-weighted imaging (IVIM DWI). METHODS: Patients with pathologically proven rectal adenocarcinoma underwent routine high-resolution rectal magnetic resonance imaging (MRI) and IVIM DWI sequences were acquired. The MRI-detected circumferential resection margin (mrCRM) and extramural vascular invasion (mrEMVI) were evaluated. IVIM parameters of the mesorectum adjacent to (MAT) and distant from (MDT) the tumour were measured and compared between and within the prognostic factor groups. RESULTS: The positive mrCRM (pMAT < 0.001; pMDT = 0.013) and mrEMVI (pMAT = 0.001; pMDT < 0.001) groups demonstrated higher D values in the MAT and MDT than the corresponding negative groups. Conversely, the positive mrCRM (p = 0.001) and mrEMVI (p < 0.001) groups both demonstrated lower f values in the MAT. Similarly, in the self-comparison between the MAT and MDT in the above subgroups, D showed a significant difference in all subgroups (p < 0.001 for all), and f showed a significant difference in the positive mrCRM (p = 0.001) and mrEMVI (p = 0.002) groups. Moreover, the MAT displayed a higher D* in the positive mrCRM (p = 0.014), negative mrCRM (p = 0.009) and negative mrEMVI groups (p < 0.001). CONCLUSION: The microstructure of the mesorectum in patients with rectal cancer with poor prognostic status shows changes based on IVIM parameters. IVIM parameters might be promising imaging biomarkers for risk assessment of tumour spread in mesorectum preoperatively.

Expression Pattern of FT/TFL1 and miR156-Targeted SPL Genes Associated with Developmental Stages in Dendrobium catenatum.

Time to flower, a process either referring to juvenile-adult phase change or vegetative-reproductive transition, is strictly controlled by an intricate regulatory network involving at least both FT/TFL1 and the micro RNA (miR)156-regulated SPL family members. Despite substantial progresses recently achieved in Arabidopsis and other plant species, information regarding the involvement of these genes during orchid development and flowering competence is still limited. Dendrobium catenatum, a popular orchid species, exhibits a juvenile phase of at least three years. Here, through whole-genome mining and whole-family expression profiling, we analyzed the homologous genes of FT/TFL1, miR156, and SPL with special reference to the developmental stages. The FT/TFL1 family contains nine members; among them, DcHd3b transcribes abundantly in young and juvenile tissues but not in adult, contrasting with the low levels of others. We also found that mature miR156, encoded by a single locus, accumulated in large quantity in protocorms and declined by seedling development, coincident with an increase in transcripts of three of its targeted SPL members, namely DcSPL14, DcSPL7, and DcSPL18. Moreover, among the seven predicted miR156-targeted SPLs, only DcSPL3 was significantly expressed in adult plants and was associated with plant maturation. Our results might suggest that the juvenile phase change or maturation in this orchid plant likely involves both the repressive action of a TFL1-like pathway and the promotive effect from an SPL3-mediated mechanism.

A dense mapping study of six European AITD susceptibility regions in a large Chinese Han Cohort of Graves' disease.

OBJECTIVE: We aimed to investigate the six susceptibility loci of GD identified from European population in Chinese Han population and further to estimate the genetic heterogeneity of them in stratification of our GD patients. DESIGN: Dense mapping studies based on GWAS. PATIENTS: A total of 1536 GD patients and 1516 controls in GWAS stage and 1994 GD patients and 2085 controls and 5033 GD patients and 5389 controls in two replication stages. MEASUREMENTS: Based on our previous GWAS data, independently GD-associated SNPs in each region were identified by TagSNP analysis and logistic regression analysis. The association of these SNPs was investigated in 1994 GD patients and 2085 controls, and then, the significantly associated SNPs (P < 0.05) were further genotyped in a second cohort including 5033 GD patients and 5389 controls. RESULTS: After the first replication stage, four SNPs from three regions with Pfirst  < 0.05 were further selected and genotyped in another independent cohort. The association of two SNPs with GD was confirmed in combined Chinese cohorts: rs12575636 at 11q21 (Pcombined  = 7.55 × 10-11 , OR = 1.27) and rs1881145 in TRIB2 at 2p25.1 (Pcombined  = 5.59 × 10-8 , OR = 1.14). Further study disclosed no significant difference for these SNPs between GD subsets. However, eQTL data revealed that SESN3 could be a potential susceptibility gene of GD in 11q21 region. CONCLUSIONS: Out of the six susceptibility loci of GD identified from European population, two risk loci were confirmed in a large Chinese Han population. There is variability in GD genetic susceptibility in different ethnic groups. SESN3 is a potential susceptible gene of GD in 11q21.

Recent advances in response to environmental signals during Arabidopsis root development.

Plants grow by anchoring their roots in the soil, acquiring essential water and nutrients for growth, and interacting with other signaling factors in the soil. Root systems are crucial for both the basic growth and development of plants and their response to external environmental stimuli. Under different environmental conditions, the configuration of root systems in plants can undergo significant changes, with their strength determining the plant's ability to adapt to the environment. Therefore, understanding the mechanisms by which environmental factors regulate root development is essential for crop root architecture improvement and breeding for stress resistance. This paper summarizes the research progress in genetic regulation of root development of the model plant Arabidopsis thaliana (L.) Heynh. amidst diverse environmental stimuli over the past five years. Specifically, it focuses on the regulatory networks of environmental signals, encompassing light, energy, temperature, water, nutrients, and reactive oxygen species, on root development. Furthermore, it provides prospects for the application of root architecture improvement in crop breeding for stress resistance and nutrient efficiency.

Crosstalk among plant hormone regulates the root development.

The plant root absorbs water and nutrients, anchors the plant in the soil, and promotes plant development. Root is developed from root apical meristem (RAM), which is formed during embryo stage and is maintained by dividing stem cells. Plant hormones have a predominant role in RAM maintenance. This review evaluates the functional crosstalk among three major hormones (auxin, cytokinin, and brassinolide) in RAM development in Arabidopsis, integrating a variety of experimental data into a regulatory network and revealing multiple layers of complexity in the crosstalk among these three hormones. We also discuss possible directions for future research on the roles of hormones in regulating RAM development and maintenance.

Plant cuticles repress organ initiation and development during skotomorphogenesis in Arabidopsis.

After germination in the dark, plants produce a shoot apical hook and closed cotyledons to protect the quiescent shoot apical meristem (SAM), which is critical for seedling survival during skotomorphogenesis. The factors that coordinate these processes, particularly SAM repression, remain enigmatic. Plant cuticles, multilayered structures of lipid components on the outermost surface of the aerial epidermis of all land plants, provide protection against desiccation and external environmental stresses. Whether and how cuticles regulate plant development are still unclear. Here, we demonstrate that mutants of BODYGUARD1 (BDG1) and long-chain acyl-CoA synthetase2 (LACS2), key genes involved in cutin biosynthesis, produce a short hypocotyl with an opened apical hook and cotyledons in which the SAM is activated during skotomorphogenesis. Light signaling represses expression of BDG1 and LACS2, as well as cutin biosynthesis. Transcriptome analysis revealed that cuticles are critical for skotomorphogenesis, particularly for the development and function of chloroplasts. Genetic and molecular analyses showed that decreased HOOKLESS1 expression results in apical hook opening in the mutants. When hypoxia-induced expression of LITTLE ZIPPER2 at the SAM promotes organ initiation in the mutants, the de-repressed expression of cell-cycle genes and the cytokinin response induce the growth of true leaves. Our results reveal previously unrecognized developmental functions of the plant cuticle during skotomorphogenesis and demonstrate a mechanism by which light initiates photomorphogenesis through dynamic regulation of cuticle synthesis to induce coordinated and systemic changes in organ development and growth during the skotomorphogenesis-to-photomorphogenesis transition.

The association between gestational weight trajectories in women with gestational diabetes and their offspring's weight from birth to 40 months.

AIMS: To identify the gestational weight gain (GWG) patterns in women with gestational diabetes mellitus (GDM) and evaluate their association with offspring weight status from birth to 40 months. MATERIALS AND METHODS: This study included 2,723 GDM-mother-child pairs from the Beijing Birth Cohort Study. The association between GWG trajectories identified by the latent class model and offspring weight outcomes from birth to 40 months were evaluated, after adjustment for maternal age, parity, pre-pregnancy body mass index, maternal height, and blood glucose levels. RESULTS: Three GWG rate groups, including the non-excessive GWG group (1,994/2,732), excessive GWG group (598 /2,732), and excessive early GWG group (140/2,732), were identified in women with GDM, respectively. Compared to the non-excessive GWG group, the adjusted OR (aOR) and 95% CI were 1.83 (1.35-2.47) and 1.79 (1.06-3.01) for macrosomia, 1.33 (1.07-1.66) and 1.48 (1.01-2.17) for large for gestational age (LGA) in the excessive GWG group and excessive early GWG group. Excessive GWG was also associated with an increased risk of BMI-for-age at 40 months (aOR = 1.66, 95% CI 1.14-2.42). CONCLUSIONS: Both excessive GWG and excessive early GWG increased the risk of macrosomia and LGA in women with GDM, but only the excessive GWG was associated with childhood overweight/obesity. The results suggest the long-term impact of GWG on offspring weight status in women with GDM and the potential benefits of GWG restriction after GDM diagnosis.

Value of orthogonal axial MR images in preoperative T staging of gastric cancer.

PURPOSE: To assess the value of orthogonal axial images (OAI) of MRI in gastric cancer T staging. METHODS: This retrospective study enrolled 133 patients (median age, 63 [range, 24-85] years) with gastric adenocarcinoma who underwent both CT and MRI followed by surgery. MRI lacking or incorporating OAI and CT images were evaluated, respectively. Diagnostic performance (accuracy, sensitivity, and specificity) for each T stage, overall diagnostic accuracy and rates of over- and understaging were quantified employing pathological T stage as a reference standard. The McNemar's test was performed to compare the overall accuracy. RESULTS: Among patients with pT1-pT4 disease, MRI with OAI (accuracy: 88.7-94.7%, sensitivity: 66.7-93.0%, specificity: 91.5-100.0%) exhibited superior diagnostic performance compared to MRI without OAI (accuracy: 81.2-88.7%, sensitivity: 46.2-83.1%, specificity: 85.5-99.1%) and CT (accuracy: 88.0-92.5%, sensitivity: 53.3-90.1%, specificity: 88.7-98.1%). The overall accuracy of MRI with OAI was significantly higher (83.5%) than that of MRI without OAI (67.7%) (p < .001). However, there was no significant difference in the overall accuracy of MRI with OAI and CT (78.9%) (p = .35). The over- and understaging rates of MRI with OAI (12.0, 4.5%) were lower than those of MRI without OAI (21.8, 10.5%) and CT (12.8, 8.3%). CONCLUSION: OAI play a pivotal role in the T staging of gastric cancer. MRI incorporating OAI demonstrated commendable performance for gastric cancer T-staging, with a slight tendency toward its superiority over CT.

A model worker: Multifaceted modulation of AUXIN RESPONSE FACTOR3 orchestrates plant reproductive phases.

The key phytohormone auxin is involved in practically every aspect of plant growth and development. Auxin regulates these processes by controlling gene expression through functionally distinct AUXIN RESPONSE FACTORs (ARFs). As a noncanonical ARF, ARF3/ETTIN (ETT) mediates auxin responses to orchestrate multiple developmental processes during the reproductive phase. The arf3 mutation has pleiotropic effects on reproductive development, causing abnormalities in meristem homeostasis, floral determinacy, phyllotaxy, floral organ patterning, gynoecium morphogenesis, ovule development, and self-incompatibility. The importance of ARF3 is also reflected in its precise regulation at the transcriptional, posttranscriptional, translational, and epigenetic levels. Recent studies have shown that ARF3 controls dynamic shoot apical meristem (SAM) maintenance in a non-cell autonomous manner. Here, we summarize the hierarchical regulatory mechanisms by which ARF3 is regulated and the diverse roles of ARF3 regulating developmental processes during the reproductive phase.

Dynamic changes in blood lipid levels and their associations with hypertensive disorders of pregnancy in twin pregnancy: A retrospective study.

BACKGROUND: Little knowledge on the association of blood lipid levels with hypertensive disorders of pregnancy (HDP) in twin pregnancy. OBJECTIVE: To investigate the association of blood lipid levels with HDP in twin pregnancy. METHODS: This is a retrospective study in the Beijing Birth Cohort on patients followed between January 2014 and November 2021. A total of 2628 women pregnant with twins were included and divided into HDP (n = 565) and normal blood pressure (NBP, n = 2063) groups. HDP subtypes included gestational hypertension (GH, n = 190) and preeclampsia (PE, n = 375). Dynamic changes in blood lipid profiles and their associations with HDP were assessed. RESULTS: Compared to NBP group, higher triglyceride (TG) and low-density lipoprotein  cholesterol (LDL-c) in the first (T1) and second trimesters (T2) existed in women with PE. In addition, TG increased significantly from T1 to T2, and high-density lipoprotein cholesterol (HDL-c) decreased significantly since T2 in women with PE, especially in women with early-onset PE and severe PE. Elevated TG and LDL-c were associated with HDP, mainly PE. In a subgroup analysis, higher TG or LDL-c increased the risk of HDP for underweight, overweight and primipara women. CONCLUSIONS: In twin pregnancy, women with PE had higher TG and LDL-c, and elevated TG and LDL-c were associated with PE. A significant increase in TG or decrease in HDL-c were more prone to PE, especially early-onset PE and severe PE. It is helpful to monitor blood lipid levels in women pregnant with twins, especially in underweight, overweight, and primipara women.

A novel gene therapy for methamphetamine- induced cognitive disorder with a hyper-acidified fusion variant of DnaJB1.

Methamphetamine (MA) is spread worldwide and is a highly addictive psychostimulant that can induce neurodegeneration and cognitive disorder, which lacks effective treatments. We and other researchers have found that the crucial member of Hsp70 chaperone machinery, DnaJ, is liable to be co-aggregated with aberrant proteins, which has been confirmed a risk factor to promote neurodegeneration. In the current study, we demonstrated that tailing with a hyper-acidic fusion partner, tua2, human DnaJB1 could resist the formation of toxic mutant Tau aggregates both in prokaryote and eukaryote models. We found that aberrant Tau aggregates could deplete the antioxidant enzyme pool and disturb Hsp70 molecular chaperone system by co-aggregating with the principal members of these systems. Stability-enhanced DnaJB1-tua2 could stop the chain reaction of Tau aggregates as well as maintain redox balance and protein homeostasis. With an MA-induced cognitive disorder mouse model, we found that the cognitive disorder of MA mice was rescued and the overactivated inflammatory response was relieved by the expression of DnaJB1-tua2 in the hippocampus. Furthermore, the Tau neurofibrillary tangles and apoptotic neurons were diminished with the escorting of DnaJB1-tua2. These findings demonstrate that delivering DnaJB1-tua2 in hippocampus may have a therapeutic potential in the treatment of MA-induced cognitive disorder.

MRI for nodal restaging after neoadjuvant therapy in rectal cancer with histopathologic comparison.

BACKGROUND: After neoadjuvant therapy, most of the lymph nodes (LNs) will shrink and disappear in patients with rectal cancer. However, LNs that are still detectable on MRI carry a risk of metastasis. This study aimed to evaluate the performance of the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) criterion (short-axis diameter ≥ 5 mm) in diagnosing malignant LNs in patients with rectal cancer after neoadjuvant therapy, and whether nodal morphological characteristics (including shape, border, signal homogeneity, and enhancement homogeneity) could improve the diagnostic efficiency for LNs ≥ 5 mm. METHODS: This retrospective study included 90 patients with locally advanced rectal cancer who underwent surgery after neoadjuvant therapy and performed preoperative MRI. Two radiologists independently measured the short-axis diameter of LNs and evaluated the morphological characteristics of LNs ≥ 5 mm in consensus. With a per node comparison with histopathology as the reference standard, a ROC curve was performed to evaluate the diagnostic performance of the size criterion. For categorical variables, either a χ2 test or Fisher's exact test was used. RESULTS: A total of 298 LNs were evaluated. The AUC for nodal size in determining nodal status was 0.81. With a size cutoff value of 5 mm, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 65.9%, 87.0%, 46.8%, 93.6% and 83.9%, respectively. No significant differences were observed in any of the morphological characteristics between benign and malignant LNs ≥ 5 mm (all P > 0.05). CONCLUSIONS: The ESGAR criterion demonstrated moderate diagnostic performance in identifying malignant LNs in patients with rectal cancer after neoadjuvant therapy. It was effective in determining the status of LNs < 5 mm but not for LNs ≥ 5 mm, and the diagnostic efficiency could not be improved by considering nodal morphological characteristics.

Environmental F actors coordinate circadian clock function and rhythm to regulate plant development.

Changes in the external environment necessitate plant growth plasticity, with environmental signals such as light, temperature, and humidity regulating growth and development. The plant circadian clock is a biological time keeper that can be "reset" to adjust internal time to changes in the external environment. Exploring the regulatory mechanisms behind plant acclimation to environmental factors is important for understanding how plant growth and development are shaped and for boosting agricultural production. In this review, we summarize recent insights into the coordinated regulation of plant growth and development by environmental signals and the circadian clock, further discussing the potential of this knowledge.

Variations in the morphological and chemical composition of the rhizomes of Polygonatum species based on a common garden experiment.

Polygonatum species have great potential in fighting chronic and hidden hunger. In this study, five Polygonatum species collected from different populations were cultivated in a common garden for 4 years. The species mainly differed in yield, saponin and polysaccharide contents, stem diameter, leaf width, inflorescence length, and floret inflorescence length. P. cyrtonema (PC) provides high-quality yield when planted in Zhejiang, with output as high as 7.5 tons per hectare and a promising breeding potential. Moreover, stem diameter can be used as an indicator of the harvest in the screening of varieties. In addition, the formation of plant genetic traits from different provenances is affected by the climatic factors of the origin. Furthermore, near-infrared spectroscopy combined with chemometrics for polysaccharide and saponin quantitation provides a rapid assessment of PC quality. Our findings provide a scientific basis for the development and sustainable utilization of PC as a high-yielding and high-quality forest crop.

Association of Maternal Plasma Manganese with the Risk of Spontaneous Preterm Birth: A Nested Case-Control Study Based on the Beijing Birth Cohort Study (BBCS) in China.

We performed this study to clarify the dynamic changes in maternal manganese (Mn) concentration during pregnancy and its association with spontaneous preterm birth (SPB). A nested case-control study was conducted based on the Beijing Birth Cohort Study (BBCS) from 2018 to 2020. Singleton pregnancy women aged 18-44 (n = 488) were involved in the study, including 244 cases of SPB and 244 controls. All of the participants provided blood samples twice (in their first and third trimesters). Inductively coupled plasma mass spectrometry (ICP-MS) was used for the laboratory analysis, and unconditional logistic regression was used for the statistical analysis. We found that the maternal Mn levels were significantly higher in the third trimester than those in the first trimester (median: 1.23 vs. 0.81 ng/mL). The SPB risk was increased to 1.65 (95% CI: 1.04-2.62, p = 0.035) in the highest Mn level (third tertile) in the third trimester, especially in normal-weight women (OR: 2.07, 95% CI: 1.18-3.61, p = 0.011) or non-premature rupture of membrane (PROM) women (OR: 3.93, 95% CI: 2.00-7.74, p < 0.001). Moreover, a dose-dependent relationship exists between the SPB risk and maternal Mn concentration in non-PROM women (P trend < 0.001). In conclusion, dynamic monitoring of maternal Mn level during pregnancy would be helpful for SPB prevention, especially in normal-weight and non-PROM women.