Association between loneliness and mild cognitive impairment in older adults: a meta-analysis of longitudinal studies.

OBJECTIVES: Prior studies reporting the effects of loneliness on mild impairment cognitive (MCI) have generated inconsistent results. This meta-analysis aimed to investigate the longitudinal association between loneliness and risk of MCI among community-dwelling middle-aged and older adults. METHOD: Five electronic databases were searched from inception to 9 May 2023. Eligible studies examined the longitudinal association between loneliness and cognitive outcomes, including incident MCI, cognitive impairment, and cognitive decline. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects meta-analysis. Sensitivity analysis and subgroup analysis were conducted. Publication bias was examined using Egger's and Begg tests. RESULTS: Eight studies were included. Among the 45,032 participants, 10,570 were diagnosed with MCI/cognitive decline. Loneliness was positively associated with an increased risk of MCI (overall OR = 1.14; 95% CI = 1.05, 1.23), with moderate heterogeneity (I2 = 44.2%). Sensitivity analysis have minimal influence on the aforementioned pooled effect. Subgroup analyses indicated stronger associations in studies which employed incident MCI as cognitive outcome (OR = 2.55, 95%CI = 1.31, 1.83), were conducted in non-Asia countries (OR = 1.52, 95%CI = 0.95, 1.20), and reported no depression adjustment (OR = 1.51, 95%CI = 1.04, 1.25). The association between loneliness and MCI was stronger among males compare to females. The Egger test and Begg test showed no evidence of significant publication bias (p = .493; p = .474). CONCLUSION: The findings indicated that loneliness was associated with an increased risk of MCI. Future longitudinal studies should evaluate potential cases of MCI through comprehensive clinical assessments by practitioners to draw robust findings on the association of loneliness with MCI.

Loneliness was associated with an increased risk of MCI in older adults.The association between loneliness and MCI was stronger in the males compared to the females.Future studies are warranted to assess loneliness by validated scales and clinical assessments of MCI.

Single-Atom-Based Nanoenzyme in Tissue Repair.

Since the discovery of ferromagnetic nanoparticles Fe3O4 that exhibit enzyme-like activity in 2007, the research on nanoenzymes has made significant progress. With the in-depth study of various nanoenzymes and the rapid development of related nanotechnology, nanoenzymes have emerged as a promising alternative to natural enzymes. Within nanozymes, there is a category of metal-based single-atom nanozymes that has been rapidly developed due to low cast, convenient preparation, long storage, less immunogenicity, and especially higher efficiency. More importantly, single-atom nanozymes possess the capacity to scavenge reactive oxygen species through various mechanisms, which is beneficial in the tissue repair process. Herein, this paper systemically highlights the types of metal single-atom nanozymes, their catalytic mechanisms, and their recent applications in tissue repair. The existing challenges are identified and the prospects of future research on nanozymes composed of metallic nanomaterials are proposed. We hope this review will illuminate the potential of single-atom nanozymes in tissue repair, encouraging their sequential clinical translation.

Acceptor-donor-acceptor-type molecules with large electrostatic potential difference for effective NIR photothermal therapy.

Although acceptor-donor-acceptor (A-D-A)-type molecules offer advantages in constructing NIR absorbing photothermal agents (PTAs) due to their strong intramolecular charge transfer and molecular planarity, their applications in photothermal therapy (PTT) of tumors remain insufficiently explored. In particular, the influence of ESP distribution on the optical properties of A-D-A photosensitizers has not been investigated. Herein, we analyze and compare the difference in ESP distribution between A-D-A-type small molecules and polymers to construct NIR absorbing PTAs with a high extinction coefficient (ε) and high photothermal conversion efficiency (PCE). The calculation results of density functional theory (DFT) indicate that the large ESP difference makes A-D-A-type small molecules superior to their polymer counterparts in realizing tight molecular packing and strong NIR absorbance. Among the as-prepared nanoparticles (NPs), Y6 NPs exhibited an obvious bathochromic shift of absorption peak from 711 nm to 822 nm, with the NIR-II emission extended to 1400 nm. Moreover, a high ε value of 5.69 L g-1 cm-1 and a PCE of 66.3% were attained, making Y6 NPs suitable for PTT. With a concentration of 100 µg mL-1, Y6 NPs in aqueous dispersion yielded a death rate of 93.4% for 4T1 cells upon 808 nm laser irradiation (1 W cm-2) for 10 min, which is comparable with the best results of recently reported PTT agents.

Liraglutide attenuates type 2 diabetes mellitus-associated non-alcoholic fatty liver disease by activating AMPK/ACC signaling and inhibiting ferroptosis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of type 2 diabetes mellitus (T2DM). The pathogenesis of NAFLD involves multiple biological changes, including insulin resistance, oxidative stress, inflammation, as well as genetic and environmental factors. Liraglutide has been used to control blood sugar. But the impact of liraglutide on T2DM-associated NAFLD remains unclear. In this study, we investigated the impact and potential molecular mechanisms of inhibiting ferroptosis for liraglutide improves T2DM-associated NAFLD. METHODS: Mice were fed on high-fat-diet and injected with streptozotocin to mimic T2DM-associated NAFLD and gene expression in liver was analysed by RNA-seq. The fast blood glucose was measured during the period of liraglutide and ferrostatin-1 administration. Hematoxylin and eosin staining was used to evaluate the pathological changes in the liver. The occurrence of hepatic ferroptosis was measured by lipid peroxidation in vivo. The mechanism of liraglutide inhibition ferroptosis was investigated by in vitro cell culture. RESULTS: Liraglutide not only improved glucose metabolism, but also ameliorated tissue damage in the livers. Transcriptomic analysis indicated that liraglutide regulates lipid metabolism related signaling including AMPK and ACC. Furthermore, ferroptosis inhibitor rather than other cell death inhibitors rescued liver cell viability in the presence of high glucose. Mechanistically, liraglutide-induced activation of AMPK phosphorylated ACC, while AMPK inhibitor compound C blocked the liraglutide-mediated suppression of ferroptosis. Moreover, ferroptosis inhibitor restored liver function in T2DM mice in vivo. CONCLUSIONS: These findings indicate that liraglutide ameliorates the T2DM-associated NAFLD, which possibly through the activation of AMPK/ACC pathway and inhibition of ferroptosis.

Weight change across adulthood in relation to the risk of depression.

Background: Studies examining weight change patterns and depression are scarce and report inconsistent findings. This study-aimed to elucidate the association between weight change patterns and the risk of depression in a large, representative sample of US adults. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 was analyzed. Five weight change groups were categorized: stable normal, weight loss, weight gain, maximum overweight, and stable obesity. Depression was ascertained using the validated Patient Health Questionnaire (PHQ-9) and depression was defined as PHQ score ≥ 10. Results: A total of 17,556 participants were included. Compared with participants who maintained normal weight, stable obesity participants had increased risks of depression across adulthood from age 25 years to 10 years before the survey (OR = 1.61, 95% CI =1.23 to 2.11), in the 10 years period before the survey (OR = 2.15, 95% CI =1.71 to 2.70), and from age 25 years to survey (OR = 1.88, 95% CI =1.44 to 2.44). Weight gain was associated with an increased risk of depression from age 25 years to 10 years before the survey (OR = 1.71, 95% CI = 1.41 to 2.04), in the 10 years period before the survey (OR = 1.73, 95% CI = 1.35 to 2.21), and for the period from age 25 years to survey (OR = 1.83, 95% CI = 1.49 to 2.24). In the stratified analyses, we found statistically significant interactions with sex. Conclusion: Our study suggested that stable obesity and weight gain across adulthood were associated with increased risks of depression.

Identification of risk factors for infection after mitral valve surgery through machine learning approaches.

Background: Selecting features related to postoperative infection following cardiac surgery was highly valuable for effective intervention. We used machine learning methods to identify critical perioperative infection-related variables after mitral valve surgery and construct a prediction model. Methods: Participants comprised 1223 patients who underwent cardiac valvular surgery at eight large centers in China. The ninety-one demographic and perioperative parameters were collected. Random forest (RF) and least absolute shrinkage and selection operator (LASSO) techniques were used to identify postoperative infection-related variables; the Venn diagram determined overlapping variables. The following ML methods: random forest (RF), extreme gradient boosting (XGBoost), Support Vector Machine (SVM), Gradient Boosting Decision Tree (GBDT), AdaBoost, Naive Bayesian (NB), Logistic Regression (LogicR), Neural Networks (nnet) and artificial neural network (ANN) were developed to construct the models. We constructed receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) was calculated to evaluate model performance. Results: We identified 47 and 35 variables with RF and LASSO, respectively. Twenty-one overlapping variables were finally selected for model construction: age, weight, hospital stay, total red blood cell (RBC) and total fresh frozen plasma (FFP) transfusions, New York Heart Association (NYHA) class, preoperative creatinine, left ventricular ejection fraction (LVEF), RBC count, platelet (PLT) count, prothrombin time, intraoperative autologous blood, total output, total input, aortic cross-clamp (ACC) time, postoperative white blood cell (WBC) count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), PLT count, hemoglobin (Hb), and LVEF. The prediction models for infection after mitral valve surgery were established based on these variables, and they all showed excellent discrimination performance in the test set (AUC > 0.79). Conclusions: Key features selected by machine learning methods can accurately predict infection after mitral valve surgery, guiding physicians in taking appropriate preventive measures and diminishing the infection risk.

Quality and Agronomic Trait Analyses of Pyramids Composed of Wheat Genes NGli-D2, Sec-1s and 1Dx5+1Dy10.

Due to rising living standards, it is important to improve wheat's quality traits by adjusting its storage protein genes. The introduction or locus deletion of high molecular weight subunits could provide new options for improving wheat quality and food safety. In this study, digenic and trigenic wheat lines were identified, in which the 1Dx5+1Dy10 subunit, and NGli-D2 and Sec-1s genes were successfully polymerized to determine the role of gene pyramiding in wheat quality. In addition, the effects of ω-rye alkaloids during 1BL/1RS translocation on quality were eliminated by introducing and utilizing 1Dx5+1Dy10 subunits through gene pyramiding. Additionally, the content of alcohol-soluble proteins was reduced, the Glu/Gli ratio was increased and high-quality wheat lines were obtained. The sedimentation values and mixograph parameters of the gene pyramids under different genetic backgrounds were significantly increased. Among all the pyramids, the trigenic lines in Zhengmai 7698, which was the genetic background, had the highest sedimentation value. The mixograph parameters of the midline peak time (MPT), midline peak value (MPV), midline peak width (MPW), curve tail value (CTV), curve tail width (CTW), midline value at 8 min (MTxV), midline width at 8 min (MTxW) and midline integral at 8 min (MTxI) of the gene pyramids were markedly enhanced, especially in the trigenic lines. Therefore, the pyramiding processes of the 1Dx5+1Dy10, Sec-1S and NGli-D2 genes improved dough elasticity. The overall protein composition of the modified gene pyramids was better than that of the wild type. The Glu/Gli ratios of the type I digenic line and trigenic lines containing the NGli-D2 locus were higher than that of the type II digenic line without the NGli-D2 locus. The trigenic lines with Hengguan 35 as the genetic background had the highest Glu/Gli ratio among the specimens. The unextractable polymeric protein (UPP%) and Glu/Gli ratios of the type II digenic line and trigenic lines were significantly higher than those of the wild type. The UPP% of the type II digenic line was higher than that of the trigenic lines, while the Glu/Gli ratio was slightly lower than that of the trigenic lines. In addition, the celiac disease (CD) epitopes' level of the gene pyramids significantly decreased. The strategy and information reported in this study could be very useful for improving wheat processing quality and reducing wheat CD epitopes.

The turnover dynamics of woody plants in a tropical lowland rain forest during recovery following anthropogenic disturbances.

An important indicator of forest dynamics is the forest community turnover rate, which was defined as the relative change in a variable of interest (e.g., basal area or stem abundance) to its maximum or total in the community over a certain period. Community turnover dynamics in part explain the community assembly process and give insights for understanding forest ecosystem functions. Here, we assessed how anthropogenic disturbances (shifting cultivation, clear cutting) affect turnover relative to old growth forests in a tropical lowland rainforest. Using two censuses over 5 years of twelve 1-ha forest dynamics plots (FDPs), we compared turnover dynamics of woody plant, then analyzed the influencing factors. We found that community turnover dynamics of FDPs that experienced shifting cultivation were significantly higher than those experienced clear cutting or no disturbance, but little difference between clear cutting and no disturbance. Stem mortality and relative growth rates were the highest contributors to stem and basal area turnover dynamics of woody plants, respectively. Both stem and turnover dynamics of woody plants were more consistent by the dynamics of trees (DBH≥5 cm). Canopy openness, as the most important drivers, was positively correlated with turnover rates, while soil available potassium and elevation were negatively correlated with turnover rates. We highlight the long-term impacts of major anthropogenic disturbances on tropical natural forests. Different conservation and restoration strategies should be adopted for tropical natural forests experienced different disturbance types.

Inhibiting neuronal AC1 for treating anxiety and headache in the animal model of migraine.

Migraines are a common medical condition. From a basic science point of view, the central mechanism for migraine and headache is largely unknown. In the present study, we demonstrate that cortical excitatory transmission is significantly enhanced in the anterior cingulate cortex (ACC)-a brain region which is critical for pain perception. Biochemical studies found that the phosphorylation levels of both the NMDA receptor GluN2B and AMPA receptor GluA1 were enhanced in ACC of migraine rats. Both the presynaptic release of glutamate and postsynaptic responses of AMPA receptors and NMDA receptors were enhanced. Synaptic long-term potentiation (LTP) was occluded. Furthermore, behavioral anxiety and nociceptive responses were increased, which were reversed by application of AC1 inhibitor NB001 within ACC. Our results provide strong evidence that cortical LTPs contribute to migraine-related pain and anxiety. Drugs that inhibit cortical excitation such as NB001 may serve as potential medicines for treating migraine in the future.

J-shaped association between uric acid and breast cancer risk: a prospective case-control study.

BACKGROUND/AIM: In terms of breast cancer risk, there is no consensus on the effect of uric acid (UA) levels. The aim of our study was to clarify the link between UA and breast cancer risk in a prospective case-control study and to find the UA threshold point. METHODS: We designed a case-control study with 1050 females (525 newly diagnosed breast cancer patients and 525 controls). We measured the UA levels at baseline and confirmed the incidence of breast cancer through postoperative pathology. We used binary logistic regression to study the association between breast cancer and UA. In addition, we performed restricted cubic splines to evaluate the potential nonlinear links between UA and breast cancer risk. We used threshold effect analysis to identify the UA cut-off point. RESULTS: After adjusting for multiple confounding factors, we found that compared with the referential level (3.5-4.4 mg/dl), the odds ratio (OR) of breast cancer was 1.946 (95% CI 1.140-3.321) (P < 0.05) in the lowest UA level and 2.245 (95% CI 0.946-5.326) (P > 0.05) in the highest level. Using the restricted cubic bar diagram, we disclosed a J-shaped association between UA and breast cancer risk (P-nonlinear < 0.05) after adjusting for all confounders. In our study, 3.6 mg/dl was found to be the UA threshold which acted as the optimal turning point of the curve. The OR for breast cancer was 0.170 (95% CI 0.056-0.512) to the left and 1.283 (95% CI 1.074-1.532) to the right of 3.6 mg/dl UA (P for log likelihood ratio test < 0.05). CONCLUSION: We found a J-shaped association between UA and breast cancer risk. Controlling the UA level around the threshold point of 3.6 mg/dl provides a novel insight into breast cancer prevention.

Trends in obesity and severe obesity prevalence in the United States from 1999 to 2018.

BACKGROUND: The national obesity epidemic and trend of obesity prevalence have been characterized by a series of cross-sectional surveys in the United States, however, less is known about obesity prevalence trajectory by birth cohort. This study aimed to investigate whether trends in obesity and severe obesity prevalence varied by birth cohorts among 1940s-1990s in the United States. METHODS: Using data from the National Health and Nutrition Examination Survey 1999-2018. The trends of obesity and severe obesity prevalence were conducted with synthetic birth cohort. RESULTS: There were 60 981 participants (weighted mean age, 38.1 years; female, 50.1%) assigned in 6 birth cohorts (1990s, 1980s, 1970s, 1960s, 1950s, and 1940s) over 1999-2018. The prevalence of obesity and severe obesity increased significantly with age during all birth cohorts except for the 1940s (Ptrend <0.001). For obesity, a significant positive quadratic trend was observed among 1990s birth cohort (Pnon-linearity  = 0.037), while a significant positive linear trend (Plinearity <0.001) among 1980s, 1970s, 1960s, and 1950s birth cohorts. Corresponding to same weighted mean age, the prevalence of both obesity and severe obesity in younger birth cohorts were much higher than the older birth generations. CONCLUSIONS: The continued upward trend in obesity and severe obesity prevalence by birth cohort highlighted the need for continuing focus on surveillance of body mass index and identification, implementation, and evaluation of evidence-based interventions to address this major health problem in the United States.

Digital Quantification Method for Sensitive Point-of-Care Detection of Salivary Uric Acid Using Smartphone-Assisted µPADs.

Uric acid (UA) is an important biomarker for many diseases. A sensitive point-of-care (POC) testing platform is designed for the digital quantification of salivary UA based on a colorimetric reaction on an easy-to-build smartphone-assisted microfluidic paper-based analytical device (SµPAD). UA levels are quantified according to the color intensity of Prussian blue on the SµPAD with the aid of a MATLAB code or a smartphone APP. A color correction method is specifically applied to exclude the light effect. Together with the engineering design of SµPADs, the background calibration function with the APP increases the UA sensitivity by 100-fold to reach 0.1 ppm with a linear range of 0.1-200 ppm. The assay time is less than 10 min. SµPADs demonstrate a correlation of 0.97 with a commercial UA kit for the detection of salivary UA in clinical samples. SµPADs provide a sensitive, fast, affordable, and reliable tool for the noninvasive POC quantification of salivary UA for early diagnosis of abnormal UA level-associated health conditions.

Understanding the mechanistic regulation of ferroptosis in cancer: the gene matters.

Ferroptosis has emerged as a crucial regulated cell death involved in a variety of physiological processes or pathological diseases, such as tumor suppression. Though initially being found from anticancer drug screening and considered not essential as apoptosis for growth and development, numerous studies have demonstrated that ferroptosis is tightly regulated by key genetic pathways and/or genes, including several tumor suppressors and oncogenes. In this review, we introduce the basic concepts of ferroptosis, characterized by the features of non-apoptotic, iron-dependent, and overwhelmed accumulation of lipid peroxides, and the underlying regulated circuits are considered to be pro-ferroptotic pathways. Then, we discuss several established lipid peroxidation defending systems within cells, including SLC7A11/GPX4, FSP1/CoQ, GCH1/BH4, and mitochondria DHODH/CoQ, all of which serve as anti-ferroptotic pathways to prevent ferroptosis. Moreover, we provide a comprehensive summary of the genetic regulation of ferroptosis via targeting the above-mentioned pro-ferroptotic or anti-ferroptotic pathways. The regulation of pro- and anti-ferroptotic pathways gives rise to more specific responses to the tumor cells in a context-dependent manner, highlighting the unceasing study and deeper understanding of mechanistic regulation of ferroptosis for the purpose of applying ferroptosis induction in cancer therapy.

Enhancement of behavioral nociceptive responses but not itching responses by viewing mirror images in adult mice.

Can mice recognize themselves in a mirror? The answer is unclear. Previous studies have reported that adult mice - when shown itch-like videos - demonstrated itch empathy. However, this was proven to be unreproducible in other studies. In the present study, we wanted to examine whether adult mice were able to recognize their mirror image. In our testing, we found that mice spent more time in the central area in an open field with mirrors surrounding the chamber than those in a normal open field. In a similar open field test with four mice placed in four directions, mice showed similar behavioral responses to those with mirrors. These results indicate that mice are able to recognize images in the mirror, however, they cannot distinguish their own mirror images from the mirror images of other mice. To repeat the experiments of itch empathy, we compared the itch responses of mice in the mirrored environment, to those without. No significant difference in itching responses was detected. Differently, in the case of chemical pain (formalin injection), animals' nociceptive responses to formalin during Phase II were significantly enhanced in the mirrored open field. A new format of heat map was developed to help the analysis of the trace of mice in the open field. Our results suggest that mice do recognize the presence of mice in the mirror, and their nociceptive - but not itch - responses are enhanced.

Associations of Postoperative Hemoglobin Level and Clinical Outcomes in Patients Undergoing Mitral Valve Surgery.

BACKGROUND: Postoperative hemoglobin could indicate useful information for transfusion practices. The aim of this study was to investigate the association of optimal hemoglobin level and clinical outcomes after mitral valve surgery (MVS). METHODS: This investigation was a multicenter observational cohort study including 1,518 patients undergoing mitral valve surgery from 2016 through 2018. Patients were separated into six predefined groups based on initial postoperative hemoglobin (< 7.5 g/dL, 7.5 - 8.4 g/dL, 8.5 - 9.4 g/dL, 9.5 - 10.4 g/dL, 10.5 - 11.4 g/dL, ≥ 11.5 g/dL). Multivariable regression analysis was used to adjust laboratory results and surgical features of patients to evaluate the relationships between initial hemoglobin after MVS and clinical outcomes. RESULTS: Patients with initial postoperative hemoglobin below 7.5 g/dL had longer length of stays [mean (95% confidence interval [CI]), 1.9 (1.093 - 1.367)] in comparison with the reference group of 9.5 - 10.4 g/dL. Similarly, for those with hemoglobin below 7.5 g/dL, the odds (95% CI) for secondary outcomes included myocardial infraction 11.801 (1.353 - 22.966) and thrombosis 5.113 (1.340 - 9.508). However, for clinical outcomes, there was no significant difference between the five groups with hemoglobin greater than 7.5 g/dL. CONCLUSIONS: In patients after MVS, initial postoperative hemoglobin values below 7.5 g/dL was associated with worse outcomes compared to other values. Given similar outcomes between hemoglobin more than 7.5 g/dL groups, targeting treatment to an initial postoperative hemoglobin value at the lower value may be more desirable.

Whole-brain mapping of efferent projections of the anterior cingulate cortex in adult male mice.

The anterior cingulate cortex (ACC) is a key cortical region that plays an important role in pain perception and emotional functions. Previous studies of the ACC projections have been collected primarily from monkeys, rabbits and rats. Due to technological advances, such as gene manipulation, recent progress has been made in our understanding of the molecular and cellular mechanisms of the ACC-related chronic pain and emotion is mainly obtained from adult mice. Few anatomic studies have examined the whole-brain projections of the ACC in adult mice. In the present study, we examined the continuous axonal outputs of the ACC in the whole brain of adult male mice. We used the virus anterograde tracing technique and an ultrahigh-speed imaging method of Volumetric Imaging with Synchronized on-the-fly-scan and Readout (VISoR). We created a three-dimensional (3D) reconstruction of mouse brains. We found that the ACC projected ipsilaterally primarily to the caudate putamen (CPu), ventral thalamic nucleus, zona incerta (ZI), periaqueductal gray (PAG), superior colliculus (SC), interpolar spinal trigeminal nucleus (Sp5I), and dorsal medullary reticular nucleus (MdD). The ACC also projected to contralateral brain regions, including the ACC, reuniens thalamic nucleus (Re), PAG, Sp5I, and MdD. Our results provide a whole-brain mapping of efferent projections from the ACC in adult male mice, and these findings are critical for future studies of the molecular and synaptic mechanisms of the ACC and its related network in mouse models of brain diseases.

Targeting Nutrient Dependency in Cancer Treatment.

Metabolic reprogramming is one of the hallmarks of tumor. Growing evidence suggests metabolic changes that support oncogenic progression may cause selective vulnerabilities that can be exploited for cancer treatment. Increasing demands for certain nutrients under genetic determination or environmental challenge enhance dependency of tumor cells on specific nutrient, which could be therapeutically developed through targeting such nutrient dependency. Various nutrients including several amino acids and glucose have been found to induce dependency in genetic alteration- or context-dependent manners. In this review, we discuss the extensively studied nutrient dependency and the biological mechanisms behind such vulnerabilities. Besides, existing applications and strategies to target nutrient dependency in different cancer types, accompanied with remaining challenges to further exploit these metabolic vulnerabilities to improve cancer therapies, are reviewed.

Genetic Dissection of the Mixing Properties of Wheat Flour (Triticum aestivum L.) Using Unconditional and Conditional QTL Mapping.

Wheat (Triticum aestivum L.) flour mixing properties are essential quality parameters in the dough development process. Limited research on superior alleles for mixing properties has restricted their molecular improvement, and other factors related to the complex traits have been ignored. A molecular map of 9576 polymorphic markers in the RIL population (F8:9) (Shannong01-35/Gaocheng9411) was constructed to evaluate mixing property effects in three environments. The parents were selected with markedly distinct high-molecular-weight glutenin subunits (HMW-GS). This study not only evaluated mixing properties using conventional unconditional QTL mapping but also evaluated the relationships between protein-related traits using conditional QTL mapping. The analyses identified most additive QTLs for major mixing properties on chromosomes 1A, 1B, and 1D. Two major loci (1A.1-15 and 1D-1) associated with mixing properties have confirmed the important contributions of Glu-A1 and Glu-D1 to wheat quality at the QTL level, which were mainly affected by the gluten index. Another important locus, 1B.1-24 (associated with midline peak value and midline peak width, with high phenotypic variations explained), might represent a new variation distinct from Glu-B1. The favored alleles came from Gaocheng9411. Several mixing properties shared the same QTLs (1B.1-6 and 1A.1-15), indicating tight linkage or pleiotropism. Genotype-by-environment (G×E) interactions were also investigated in the present study. The QTL results in our study may improve our understanding of the genetic interrelationships between mixing properties and protein-related traits.

Advances in BBB on Chip and Application for Studying Reversible Opening of Blood-Brain Barrier by Sonoporation.

The complex structure of the blood-brain barrier (BBB), which blocks nearly all large biomolecules, hinders drug delivery to the brain and drug assessment, thus decelerating drug development. Conventional in vitro models of BBB cannot mimic some crucial features of BBB in vivo including a shear stress environment and the interaction between different types of cells. There is a great demand for a new in vitro platform of BBB that can be used for drug delivery studies. Compared with in vivo models, an in vitro platform has the merits of low cost, shorter test period, and simplicity of operation. Microfluidic technology and microfabrication are good tools in rebuilding the BBB in vitro. During the past decade, great efforts have been made to improve BBB penetration for drug delivery using biochemical or physical stimuli. In particular, compared with other drug delivery strategies, sonoporation is more attractive due to its minimized systemic exposure, high efficiency, controllability, and reversible manner. BBB on chips (BOC) holds great promise when combined with sonoporation. More details and mechanisms such as trans-endothelial electrical resistance (TEER) measurements and dynamic opening of tight junctions can be figured out when using sonoporation stimulating BOC, which will be of great benefit for drug development. Herein, we discuss the recent advances in BOC and sonoporation for BBB disruption with this in vitro platform.

Oxytocin in the anterior cingulate cortex attenuates neuropathic pain and emotional anxiety by inhibiting presynaptic long-term potentiation.

Oxytocin is a well-known neurohypophysial hormone that plays an important role in behavioral anxiety and nociception. Two major forms of long-term potentiation, presynaptic LTP (pre-LTP) and postsynaptic LTP (post-LTP), have been characterized in the anterior cingulate cortex (ACC). Both pre-LTP and post-LTP contribute to chronic-pain-related anxiety and behavioral sensitization. The roles of oxytocin in the ACC have not been studied. Here, we find that microinjections of oxytocin into the ACC attenuate nociceptive responses and anxiety-like behavioral responses in animals with neuropathic pain. Application of oxytocin selectively blocks the maintenance of pre-LTP but not post-LTP. In addition, oxytocin enhances inhibitory transmission and excites ACC interneurons. Similar results are obtained by using selective optical stimulation of oxytocin-containing projecting terminals in the ACC in animals with neuropathic pain. Our results demonstrate that oxytocin acts on central synapses and reduces chronic-pain-induced anxiety by reducing pre-LTP.