bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutral Processes Provide an Insight Into the Structure and Function of Gut Microbiota in the Cotton Bollworm
Authors: Li Sali , Tang Rui , Yi Hao , Cao Zhichao , Sun Shaolei , Liu Tong-Xian , Zhang Sicong , Jing Xiangfeng
Published: May 2022

Gut-associated microbes can influence insect health and fitness. Understanding the structure of bacterial communities provides valuable insights on how different species may be selected and their functional characteristics in their hosts. The neutral model is powerful in predicting the structure of microbial communities, but its application in insects remains rare. Here, we examined the contribution of neutral processes to the gut-associated bacterial communities in Helicoverpa armigera caterpillars collected from different maize varieties at four locations. The gut-associated bacteria can be assigned to 37 Phyla, 119 orders, and 515 genera, with each individual gut containing 17–75% of the OTUs and 19–79% of the genera in the pooled samples of each population. The distribution patterns of most (75.59–83.74%) bacterial taxa were in good agreement with the neutral expectations. Of the remaining OTUs, some were detected in more individual hosts than would be predicted by the neutral model (i.e., above-partition), and others were detected in fewer individual hosts than predicted by the neutral model (i.e., below-partition). The bacterial taxa in the above-partitions were potentially selected by the caterpillar hosts, while the bacteria in the below-partitions may be preferentially eliminated by the hosts. Moreover, the gut-associated microbiota seemed to vary between maize varieties and locations, so ecological parameters outside hosts can affect the bacterial communities. Therefore, the structure of gut microbiota in the H. armigera caterpillar was mainly determined by stochastic processes, and the bacteria in the above-partition warrant further investigation for their potential roles in the caterpillar host.
Neural Bases of Age-Related Sensorimotor Slowing in the Upper and Lower Limbs
Authors: Marusic Uros , Peskar Manca , De Pauw Kevin , Omejc Nina , Drevensek Gorazd , Rojc Bojan , Pisot Rado , Kavcic Voyko
Published: May 2022

With advanced age, there is a loss of reaction speed that may contribute to an increased risk of tripping and falling. Avoiding falls and injuries requires awareness of the threat, followed by selection and execution of the appropriate motor response. Using event-related potentials (ERPs) and a simple visual reaction task (RT), the goal of our study was to distinguish sensory and motor processing in the upper- and lower-limbs while attempting to uncover the main cause of age-related behavioral slowing. Strength (amplitudes) as well as timing and speed (latencies) of various stages of stimulus- and motor-related processing were analyzed in 48 healthy individuals (young adults, n = 24, mean age = 34 years; older adults, n = 24, mean age = 67 years). The behavioral results showed a significant age-related slowing, where the younger compared to older adults exhibited shorter RTs for the upper- (222 vs. 255 ms; p = 0.006, respectively) and the lower limb (257 vs. 274 ms; p = 0.048, respectively) as well as lower variability in both modalities (p = 0.001). Using ERP indices, age-related slowing of visual stimulus processing was characterized by overall larger amplitudes with delayed latencies of endogenous potentials in older compared with younger adults. While no differences were found in the P1 component, the later components of recorded potentials for visual stimuli processing were most affected by age. This was characterized by increased N1 and P2 amplitudes and delayed P2 latencies in both upper and lower extremities. The analysis of motor-related cortical potentials (MRCPs) revealed stronger MRCP amplitude for upper- and a non-significant trend for lower limbs in older adults. The MRCP amplitude was smaller and peaked closer to the actual motor response for the upper- than for the lower limb in both age groups. There were longer MRCP onset latencies for lower- compared to upper-limb in younger adults, and a non-significant trend was seen in older adults. Multiple regression analyses showed that the onset of the MRCP peak consistently predicted reaction time across both age groups and limbs tested. However, MRCP rise time and P2 latency were also significant predictors of simple reaction time, but only in older adults and only for the upper limbs. Our study suggests that motor cortical processes contribute most strongly to the slowing of simple reaction time in advanced age. However, late-stage cortical processing related to sensory stimuli also appears to play a role in upper limb responses in the elderly. This process most likely reflects less efficient recruitment of neuronal resources required for the upper and lower extremity response task in older adults.
ProBDNF and Brain-Derived Neurotrophic Factor Prodomain Differently Modulate Acetylcholine Release in Regenerating and Mature Mouse Motor Synapses
Authors: Bogacheva Polina O. , Molchanova Anastasia I. , Pravdivceva Ekaterina S. , Miteva Anna S. , Balezina Olga P. , Gaydukov Alexander E.
Published: May 2022

The effects of brain-derived neurotrophic factor (BDNF) processing by-products (proBDNF and BDNF prodomain) on the activity of mouse neuromuscular junctions (NMJs) were studied in synapses formed during the reinnervation of extensor digitorum longus muscle (m. EDL) and mature synapses of the diaphragm. The parameters of spontaneous miniature endplate potentials (MEPPs) and evoked endplate potentials (EPPs) were analyzed in presence of each of the BDNF maturation products (both – 1 nM). In newly formed NMJs, proBDNF caused an increase in the resting membrane potential of muscle fibers and a decrease in the frequency of MEPPs, which was prevented by tertiapin-Q, a G-protein-coupled inwardly rectifying potassium channels (GIRK) blocker but not by p75 receptor signaling inhibitor TAT-Pep5. proBDNF had no effect on the parameters of EPPs. BDNF prodomain in newly formed synapses had effects different from those of proBDNF: it increased the amplitude of MEPPs, which was prevented by vesamicol, an inhibitor of vesicular acetylcholine (ACh) transporter; and reduced the quantal content of EPPs. In mature NMJs, proBDNF did not influence MEPPs parameters, but BDNF prodomain suppressed both spontaneous and evoked ACh release: decreased the frequency and amplitude of MEPPs, and the amplitude and quantal content of EPPs. This effect of the BDNF prodomain was prevented by blocking GIRK channels, by TAT-Pep5 or by Rho-associated protein kinase (ROCK) inhibitor Y-27632. At the same time, the BDNF prodomain did not show any inhibitory effects in diaphragm motor synapses of pannexin 1 knockout mice, which have impaired purinergic regulation of neuromuscular transmission. The data obtained suggest that there is a previously unknown mechanism for the acute suppression of spontaneous and evoked ACh release in mature motor synapses, which involves the activation of p75 receptors, ROCK and GIRK channels by BDNF prodomain and requires interaction with metabotropic purinoreceptors. In general, our results show that both the precursor of BDNF and the product of its maturation have predominantly inhibitory effects on spontaneous and evoked ACh release in newly formed or functionally mature neuromuscular junctions, which are mainly opposite to the effects of BDNF. The inhibitory influences of both proteins related to brain neurotrophin are mediated via GIRK channels of mouse NMJs.
Shape Trumps Size: Image-Based Morphological Analysis Reveals That the 3D Shape Discriminates Intracranial Aneurysm Disease Status Better Than Aneurysm Size
Authors: Juchler Norman , Schilling Sabine , Bijlenga Philippe , Kurtcuoglu Vartan , Hirsch Sven
Published: May 2022

Background

To date, it remains difficult for clinicians to reliably assess the disease status of intracranial aneurysms. As an aneurysm's 3D shape is strongly dependent on the underlying formation processes, it is believed that the presence of certain shape features mirrors the disease status of the aneurysm wall. Currently, clinicians associate irregular shape with wall instability. However, no consensus exists about which shape features reliably predict instability. In this study, we present a benchmark to identify shape features providing the highest predictive power for aneurysm rupture status.

Methods

3D models of aneurysms were extracted from medical imaging data (3D rotational angiographies) using a standardized protocol. For these aneurysm models, we calculated a set of metrics characterizing the 3D shape: Geometry indices (such as undulation, ellipticity and non-sphericity); writhe- and curvature-based metrics; as well as indices based on Zernike moments. Using statistical learning methods, we investigated the association between shape features and aneurysm disease status. This processing was applied to a clinical dataset of 750 aneurysms (261 ruptured, 474 unruptured) registered in the AneuX morphology database. We report here statistical performance metrics [including the area under curve (AUC)] for morphometric models to discriminate between ruptured and unruptured aneurysms.

Results

The non-sphericity index NSI (AUC = 0.80), normalized Zernike energies ZNsurf (AUC = 0.80) and the modified writhe-index W¯meanL1 (AUC = 0.78) exhibited the strongest association with rupture status. The combination of predictors further improved the predictive performance (without location: AUC = 0.82, with location AUC = 0.87). The anatomical location was a good predictor for rupture status on its own (AUC = 0.78). Different protocols to isolate the aneurysm dome did not affect the prediction performance. We identified problems regarding generalizability if trained models are applied to datasets with different selection biases.

Conclusions

Morphology provided a clear indication of the aneurysm disease status, with parameters measuring shape (especially irregularity) being better predictors than size. Quantitative measurement of shape, alone or in conjunction with information about aneurysm location, has the potential to improve the clinical assessment of intracranial aneurysms.
Efficacy and Safety of Zolpidem for Focal Dystonia After Neurosurgical Treatments: A Retrospective Cohort Study
Authors: Horisawa Shiro , Kohara Kotaro , Ebise Hiroki , Nishitani Masahiko , Kawamata Takakazu , Taira Takaomi
Published: May 2022

Although there are several reports of the significant efficacy of zolpidem for treating dystonia, zolpidem is still considered an anecdotal treatment. Here, we evaluated the efficacy and safety of zolpidem for treating residual dystonia in patients who previously received various neurosurgical treatments majorly including deep brain stimulation and radiofrequency ablation. We retrospectively reviewed medical records from January 2021 to September 2021 to identify patients with dystonia who had been prescribed zolpidem after undergoing neurosurgery. Twenty patients were enrolled in this study, including those with blepharospasm (two), tongue dystonia (four), mouth dystonia (one), spasmodic dysphonia (two), cervical dystonia (six), focal hand dystonia (three), hemidystonia (two), blepharospasm with cervical dystonia (one), and mouth dystonia with cervical dystonia (one). Single doses of zolpidem ranged between 2.5 and 10 mg, while daily dosages ranged from 10 to 30 mg. The zolpidem dose prescribed was 5–10 mg, with single and daily doses of 7 ± 2.9 and 14.5 ± 6.0 mg, respectively. With zolpidem administration, the participants' Burke-Fahn-Marsden Dystonia Rating Scale-Movement Scale score significantly improved from 8.1 ± 6.7 to 3.7 ± 2.5 (50.6% improvement, p < 0.0001). Improvements in arm dystonia, blepharospasm, and spasmodic dysphonia were observed using the Arm Dystonia Disability Scale, Jankovic Rating Scale, and Voice Handicap Index, respectively. No improvements were observed in cervical dystonia on the Toronto Western Spasmodic Torticollis Rating Scale. Drowsiness, including three cases each of mild and moderate drowsiness, was the most frequent adverse effect (30%), which persisted for 2–3 h. Transient amnesia and rapid eye movement sleep behavior disorder occurred in two patients and one patient, respectively. Although our findings suggest that zolpidem can be a valuable treatment option for patients with residual dystonia after neurosurgical treatments, the beneficial effects for cervical dystonia were limited.
Ear-EEG Measures of Auditory Attention to Continuous Speech
Authors: Holtze Björn , Rosenkranz Marc , Jaeger Manuela , Debener Stefan , Mirkovic Bojana
Published: May 2022

Auditory attention is an important cognitive function used to separate relevant from irrelevant auditory information. However, most findings on attentional selection have been obtained in highly controlled laboratory settings using bulky recording setups and unnaturalistic stimuli. Recent advances in electroencephalography (EEG) facilitate the measurement of brain activity outside the laboratory, and around-the-ear sensors such as the cEEGrid promise unobtrusive acquisition. In parallel, methods such as speech envelope tracking, intersubject correlations and spectral entropy measures emerged which allow us to study attentional effects in the neural processing of natural, continuous auditory scenes. In the current study, we investigated whether these three attentional measures can be reliably obtained when using around-the-ear EEG. To this end, we analyzed the cEEGrid data of 36 participants who attended to one of two simultaneously presented speech streams. Speech envelope tracking results confirmed a reliable identification of the attended speaker from cEEGrid data. The accuracies in identifying the attended speaker increased when fitting the classification model to the individual. Artifact correction of the cEEGrid data with artifact subspace reconstruction did not increase the classification accuracy. Intersubject correlations were higher for those participants attending to the same speech stream than for those attending to different speech streams, replicating previously obtained results with high-density cap-EEG. We also found that spectral entropy decreased over time, possibly reflecting the decrease in the listener’s level of attention. Overall, these results support the idea of using ear-EEG measurements to unobtrusively monitor auditory attention to continuous speech. This knowledge may help to develop assistive devices that support listeners separating relevant from irrelevant information in complex auditory environments.
Retrosplenial Cortex Effects Contextual Fear Formation Relying on Dysgranular Constituent in Rats
Authors: Pan Ting-Ting , Liu Chao , Li De-Min , Zhang Tian-Hao , Zhang Wei , Zhao Shi-Lun , Zhou Qi-Xin , Nie Bin-Bin , Zhu Gao-Hong , Xu Lin , Liu Hua
Published: May 2022

Animal contextual fear conditioning (CFC) models are the most-studied forms used to explore the neural substances of posttraumatic stress disorder (PTSD). In addition to the well-recognized hippocampal–amygdalar system, the retrosplenial cortex (RSC) is getting more and more attention due to substantial involvement in CFC, but with a poor understanding of the specific roles of its two major constituents—dysgranular (RSCd) and granular (RSCg). The current study sought to identify their roles and underlying brain network mechanisms during the encoding processing of the rat CFC model. Rats with pharmacologically inactivated RSCd, RSCg, and corresponding controls underwent contextual fear conditioning. [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scanning was performed for each animal. The 5-h and 24-h retrieval were followed to test the formation of contextual memory. Graph theoretic tools were used to identify the brain metabolic network involved in encoding phase, and changes of nodal (brain region) properties linked, respectively, to disturbed RSCd and RSCg were analyzed. Impaired retrieval occurred in disturbed RSCd animals, not in RSCg ones. The RSC, hippocampus (Hip), amygdala (Amy), piriform cortex (Pir), and visual cortex (VC) are hub nodes of the brain-wide network for contextual fear memory encoding in rats. Nodal degree and efficiency of hippocampus and its connectivity with amygdala, Pir, and VC were decreased in rats with disturbed RSCd, while not in those with suppressed RSCg. The RSC plays its role in contextual fear memory encoding mainly relying on its RSCd part, whose condition would influence the activity of the hippocampal–amygdalar system.
Stress Elicits Contrasting Effects on Rac1-Cofilin Signaling in the Hippocampus and Amygdala
Authors: Bose Mihika , Nawaz Mohammad Sarfaraz , Pal Rakhi , Chattarji Sumantra
Published: May 2022

There is accumulating evidence for contrasting patterns of stress-induced morphological and physiological plasticity in glutamatergic synapses of the hippocampus and amygdala. The same chronic stress that leads to the formation of dendritic spines in the basolateral amygdala (BLA) of rats, leads to a loss of spines in the hippocampus. However, the molecular underpinnings of these divergent effects of stress on dendritic spines are not well understood. Since the activity of the Rho GTPase Rac1 and the actin-depolymerizing factor cofilin are known to play a pivotal role in spine morphogenesis, we investigated if alterations in this signaling pathway reflect the differential effects of stress on spine plasticity in the hippocampus and amygdala. A day after the end of chronic immobilization stress (2 h/day for 10 days), we found a reduction in the activity of Rac1, as well as its effector p21-activated kinase 1 (PAK1), in the rat hippocampus. These changes, in turn, decreased cofilin phosphorylation alongside a reduction in the levels of profilin isoforms. In striking contrast, the same chronic stress increased Rac1, PAK1 activity, cofilin phosphorylation, and profilin levels in the BLA, which is consistent with enhanced actin polymerization leading to spinogenesis in the BLA. In the hippocampus, on the other hand, the same stress caused the opposite changes, the functional consequences of which would be actin depolymerization leading to the elimination of spines. Together, these findings reveal a role for brain-region specific differences in the dysregulation of Rac1-to-cofilin signaling in the effects of repeated stress on two brain areas that are implicated in the emotional and cognitive symptoms of stress-related psychiatric disorders.
Higher Genetically Predicted Triglycerides, LDL, and HDL Increase the Vitamin D Deficiency: A Mendelian Randomization Study
Authors: Lu Zhe , Jiao Yang , Li Jun
Published: May 2022

Introduction

It has been proven that high body mass index (BMI) levels can cause vitamin D deficiency, but the mechanism is still unclear. Therefore, this study attempts to explain this phenomenon from the perspective of blood lipid by using mendelian randomization (MR).

Methods

Genome-wide association studies (GWAS) summary datasets for serum lipids were obtained from the Global Lipids Genetics Consortium (GLGC). Vitamin D deficiency outcome data were acquired from the UK Biobank samples. Single-variable MR (SVMR) and multi-variable MR (MVMR) analyses were conducted using the TwoSampleMR package based on R 4.0.3. The four main methods were the random-effect inverse-variance weighted (IVW), MR-Egger, weighted-median method, and weighted mode.

Results

In the SVMR of serum lipid/apolipoprotein levels on serum vitamin D level, it was found that elevated serum triacylglycerol (IVW, OR = 0.85, 95%CI:0.81–0.89, P < 0.001), low-density lipoprotein (LDL) (IVW, OR = 0.93, 95%CI:0.90–0.95, P < 0.001), and high-density lipoprotein (HDL) (IVW, OR = 0.95, 95%CI:0.91–0.98, P < 0.001) levels all had a causal relationship with vitamin D deficiency, but significant pleiotropy was detected in the triacylglycerol (P = 0.001) and HDL (P = 0.003) analysis. MVMR analysis results were consistent with SVMR.

Conclusion

By using single-variable mendelian randomization and multi-variable mendelian randomization methods, we identified that the elevated serum triacylglycerol, LDL, and HDL levels all had a causal relationship with vitamin D deficiency. Taking into account the significant pleiotropy demonstrated in this study, the conclusions of this study should be treated with caution.
Food Innovation in the Frame of Circular Economy by Designing Ultra-Processed Foods Optimized for Sustainable Nutrition
Authors: Capozzi Francesco
Published: May 2022

Despite the large debate about the relationship between ultra-processed foods and the prevalence of some diet-related diseases, the innovative potential of various processing technologies has been evidenced in pathways that could lead to modifications of the food matrix with beneficial health effects. Many efforts have been directed toward the conjugation of a healthy diet and sustainable exploitation of natural resources for the preparation of accessible foods. This minireview highlights the possible links between processing, sustainability, and circular economy through the valorization of by-products that could be exploited to prepare nutrient-rich ingredients at lower economic and environmental costs. The assessment of the quality and safety of functional foods based on ingredients derived from food waste requires a more robust validation by means of the food-omics approach, which considers not only the composition of the final products but also the structural characterization of the matrix, as the bioaccessibility and the bioavailability of nutrients are strictly dependent on the functional characteristics of the innovative ingredients.
Prevalence of Helicobacter pylori in Non-Cardia Gastric Cancer in China: A Systematic Review and Meta-Analysis
Authors: Lu Yong , Xiao Fei , Wang Yuan , Wang Zhenyu , Liu Di , Hong Feng
Published: May 2022

Non-cardia gastric cancer was significantly associated with Helicobacter pylori (H. pylori) infection. Reducing H. pylori prevalence was an important prevention strategy for non-cardia gastric cancer. However, national-level data on the H. pylori prevalence in non-cardia gastric cancer were limited in China. Therefore, we conducted this study to estimate the pooled prevalence of H. pylori in non-cardia gastric cancer in China. We searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang, and VIP Database for Chinese Technical Periodicals for studies reporting H. pylori prevalence in non-cardia gastric cancer in China which were published before September 1, 2021. Pooled prevalence was calculated using a random-effect model. Subgroup analysis and meta-regression were used to explore the potential sources of heterogeneity. Egger’s test and funnel plot were used to assess publication bias. A total number of 55 studies with 5324 cases of non-cardia gastric cancer were included in this study. The pooled prevalence of H. pylori in non-cardia gastric cancer in China was 66.5% (95%CI: 62%-71%, I2=93.8%, P<0.0001). In subgroup analysis, a significant difference in the prevalence of H. pylori in non-cardia gastric cancer was noted when stratified by geographic region of China (P=0.0112). The highest H. pylori prevalence (78.9%, 95%CI: 69.9%-87.8%) was noted in Northwest China and the lowest (53.1%, 95%CI: 38.9%-67.3%) was in North China. In meta-regression, a significant association between H. pylori prevalence and geographic region was found, while type of sample, H. pylori testing method, diagnosis period, detection timing, type of study design, quality grade, publication year, and sample size were not associated with the prevalence of H. pylori in non-cardia gastric cancer (P>0.05). A large proportion of non-cardia gastric cancers were associated with H. pylori infection in China, emphasizing the possible benefits of H. pylori eradication for the prevention and control of non-cardia gastric cancer.
MiR-320b and miR-320d as Biomarkers to Predict and Participate in the Formation of Platinum Resistance in Ovarian Cancer Patients
Authors: Liu Yuan-Yuan , Zhao Ren-Feng , Liu Chao , Zhou Jie , Yang Liu , Li Li
Published: May 2022

Patients with ovarian cancer who receive platinum-based chemotherapy typically develop platinum resistance, which leads to tumor recurrence and mortality. Therefore, finding the underlying mechanisms and biomarkers is critical. A total of 51 platinum-resistant and 70 platinum-sensitive ovarian cancer patients were enrolled in this study. We examined the GSE131978 dataset in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus database for differentially expressed long non-coding RNAs and messenger RNAs (mRNAs) between platinum-resistant and platinum-sensitive patients and completed a microRNA chip analysis. After filtering by Pearson correlation analysis, the competitive endogenous RNA (ceRNA) networks were subsequently constructed. Then, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology enrichment analyses about mRNAs in ceRNA networks were accomplished. More crucially, we demonstrated the differentially expressed microRNAs using quantitative real-time PCR and fluorescence in situ hybridization. The feasibility of microRNAs as biomarkers to predict platinum resistance and tumor recurrence was assessed using the receiver operating characteristic curve and survival analysis. MiR-320b and miR-320d exhibited high area under the curve values of 0.757 and 0.702, respectively. In our study, ceRNA networks including miR-320b and miR-320d probably provided novel insights for platinum resistance in ovarian cancer patients.
Human and Economic Cost of Disease Burden Due to Congenital Hypothyroidism in India: Too Little, but Not Too Late
Authors: Vidavalur Ramesh
Published: May 2022

Background

Congenital hypothyroidism (CH) is one of the most common preventable causes of mental retardation. Implementing newborn screening (NBS) in >52 countries enabled early detection and to initiate treatment of neonates with CH. India is yet to implement a national NBS program even though an estimated 5–15% of sick newborns suffer from genetic and metabolic disorders. Recent pilot studies confirm that the CH incidence rates range from 1 in 500 to 1 in 3,400 live births. Our objective was to estimate overall incidence rates of congenital hypothyroidism and to evaluate the costs and benefits of implementing universal NBS for CH in India.

Methods

We used the best available epidemiological and cost data to synthesize incidence rates and screening costs for CH in India. We conducted a meta-analysis of country-specific published literature and included 14 studies to calculate baseline CH incidence rates. We used two models to estimate intellectual disability in unscreened cohorts. Disability-adjusted life years (DALY) were calculated to quantify burden of disease utilizing disability weights. Direct costs including screening, confirmatory tests, and treatment costs were obtained from public and private market sources. Economic benefits were calculated from lost DALY using human capital approach and value of statistical life methods, utilizing gross national income (GNI) per capita data and value of statistical life year (VSLY), respectively. Cost discounting was used to estimate the present value of future benefits over lifetime of affected newborns.

Results

The incidence rate of CH in India is 72 (95% CI: 58, 85) cases per 100,000 live births. Based on this data, 1 in 1,388 (95% CI: 1166, 1714) infants were diagnosed with CH in India for the year 2018. The estimated annual incidence ranged from 14,000 to 20,730 cases, and those at risk for intellectual disability ranged from 5,397 to 13,929 cases. Estimated discounted and undiscounted lost DALYs were 57,640 and 410,000, respectively. Direct annual costs for universal screening for CH in India is around USD187 million. Based on current incidence and expected severity of sequelae, economic losses ranged from USD 159 million to 1.1 billion. Benefit–cost ratios ranged from 1.8 to 6.

Conclusions

Universal NBS for CH is one of the healthcare interventions that is beneficial to prevent morbidity and cost saving. The cumulative economic benefits, derived from prevention of intellectual disability, assuming cost effectiveness threshold of three times of gross domestic product per capita, far outweigh the direct and indirect costs of screening, treatment, and surveillance throughout the life of the affected individuals. Our analysis strongly supports the argument for investing in NBS that provides good value for money and would yield substantial financial gains for the country.
Comprehensive Analysis of the Potential Immune-Related Biomarker ATG101 that Regulates Apoptosis of Cholangiocarcinoma Cells After Photodynamic Therapy
Authors: Zhang Zi-Jian , Wang Kun-Peng , Huang Yun-Peng , Jin Chong , Jiang Hao , Xiong Li , Chen Zhao-Yi , Wen Yu , Liu Zhong-Tao , Mo Jing-Gang
Published: May 2022

Autophagy related gene 101 (ATG101) plays a significant role in the occurrence and development of tumours by responding to stress. Our research aims to illustrate the correlation between the expression of ATG101 and tumor prognosis and its potential role and mechanism in tumor immunity and photodynamic therapy (PDT). First, integrated analysis of The Cancer Genome Atlas and Genotype-Tissue Expression portals were used to analyse the expression of ATG101. Then, Kaplan–Meier curves was applied in cholangiocarcinoma (CHOL) and liver hepatocellular carcinoma (LIHC) datasets for survival analysis. Next, the relationship between ATG101 expression and six immune cells, the immune microenvironment and immune checkpoints was analysed. Besides, the relationship between the expression of ATG101 and methyltransferase. GSEA was used to study the function and the related transcript factors of ATG101 in CHOL and LIHC. The effect of PDT on ATG101 was verified by microarray, qPCR and western blot. Then the effect of ATG101 and its regulatory factors on apoptosis were verified by siRNA, lentivirus transfection and Chip-qPCR. Comprehensive analysis showed that ATG101 was overexpressed in different tumours. Kaplan–Meier curves found that ATG101 was associated with poor prognosis in tumours (including CHOL and LIHC). We found that ATG101 can be used as a target and prognostic marker of tumour immunotherapy for different tumours. We also found that ATG101 regulates DNA methylation. GSEA analysis showed that ATG101 may play a critical role in CHOL and LIHC. Subsequent validation tests confirmed that the up-regulated ATG101 after PDT treatment is not conducive to the occurrence of apoptosis of cholangiocarcinoma cells. The high expression of ATG101 may be induced by the early stress gene EGR2. Our study highlights the significance of ATG101 in the study of tumour immunity and photodynamic therapy from a pan-cancer perspective.
Liquiritin Attenuates Pathological Cardiac Hypertrophy by Activating the PKA/LKB1/AMPK Pathway
Authors: Aiyasiding Xiahenazi , Liao Hai-Han , Feng Hong , Zhang Nan , Lin Zheng , Ding Wen , Yan Han , Zhou Zi-Ying , Tang Qi-Zhu
Published: May 2022

Background: Liquiritin (LQ) is one of the main flavonoids extracted from the roots of Glycyrrhiza spp., which are widely used in traditional Chinese medicine. Studies in both cellular and animal disease models have shown that LQ attenuates or prevents oxidative stress, inflammation, and apoptosis. However, the potential therapeutic effects of LQ on pressure overload-induced cardiac hypertrophy have not been so far explored. Therefore, we investigated the cardioprotective role of LQ and its underlying mechanisms in the aortic banding (AB)-induced cardiac hypertrophy mouse model.

Methods and Results: Starting 3 days after AB surgery, LQ (80 mg/kg/day) was administered daily over 4 weeks. Echocardiography and pressure-volume loop analysis indicated that LQ treatment markedly improved hypertrophy-related cardiac dysfunction. Moreover, hematoxylin and eosin, picrosirius red, and TUNEL staining showed that LQ significantly inhibited cardiomyocyte hypertrophy, interstitial fibrosis, and apoptosis. Western blot assays further showed that LQ activated LKB1/AMPKα2/ACC signaling and inhibited mTORC1 phosphorylation in cardiomyocytes. Notably, LQ treatment failed to prevent cardiac dysfunction, hypertrophy, and fibrosis in AMPKα2 knockout (AMPKα2−/−) mice. However, LQ still induced LKB1 phosphorylation in AMPKα2−/− mouse hearts. In vitro experiments further demonstrated that LQ inhibited Ang II-induced hypertrophy in neonatal rat cardiomyocytes (NRCMs) by increasing cAMP levels and PKA activity. Supporting the central involvement of the cAMP/PKA/LKB1/AMPKα2 signaling pathway in the cardioprotective effects of LQ, inhibition of Ang II-induced hypertrophy and induction of LKB1 and AMPKα phosphorylation were no longer observed after inhibiting PKA activity.

Conclusion: This study revealed that LQ alleviates pressure overload-induced cardiac hypertrophy in vivo and inhibits Ang II-induced cardiomyocyte hypertrophy in vitro via activating cAMP/PKA/LKB1/AMPKα2 signaling. These findings suggest that LQ might be a valuable adjunct to therapeutic approaches for treating pathological cardiac remodeling.
Cell Type-Specific Genetic Manipulation and Impaired Circadian Rhythms in ViptTA Knock-In Mice
Authors: Peng Yubo , Tsuno Yusuke , Matsui Ayako , Hiraoka Yuichi , Tanaka Kohichi , Horike Shin-ichi , Daikoku Takiko , Mieda Michihiro
Published: May 2022

The suprachiasmatic nucleus (SCN), the central circadian clock in mammals, is a neural network consisting of various types of GABAergic neurons, which can be differentiated by the co-expression of specific peptides such as vasoactive intestinal peptide (VIP) and arginine vasopressin (AVP). VIP has been considered as a critical factor for the circadian rhythmicity and synchronization of individual SCN neurons. However, the precise mechanisms of how VIP neurons regulate SCN circuits remain incompletely understood. Here, we generated ViptTA knock-in mice that express tetracycline transactivator (tTA) specifically in VIP neurons by inserting tTA sequence at the start codon of Vip gene. The specific and efficient expression of tTA in VIP neurons was verified using EGFP reporter mice. In addition, combined with Avp-Cre mice, ViptTA mice enabled us to simultaneously apply different genetic manipulations to VIP and AVP neurons in the SCN. Immunostaining showed that VIP is expressed at a slightly reduced level in heterozygous ViptTA mice but is completely absent in homozygous mice. Consistently, homozygous ViptTA mice showed impaired circadian behavioral rhythms similar to those of Vip knockout mice, such as attenuated rhythmicity and shortened circadian period. In contrast, heterozygous mice demonstrated normal circadian behavioral rhythms comparable to wild-type mice. These data suggest that ViptTA mice are a valuable genetic tool to express exogenous genes specifically in VIP neurons in both normal and VIP-deficient mice, facilitating the study of VIP neuronal roles in the SCN neural network.
Study on the Relationship of Ions (Na, K, Ca) Absorption and Distribution to Photosynthetic Response of Salix matsudana Koidz Under Salt Stress
Authors: Ran Xin , Wang Xiao , Huang Xiaoxi , Ma Changming , Liang Haiyong , Liu Bingxiang
Published: May 2022

To identify the key indicators for salt tolerance evaluation of Salix matsudana Koidz, we explored the relationship of ion absorption and distribution with chlorophyll, fluorescence parameters (leaf performance index, maximum photochemical efficiency), and photosynthetic gas parameters (net photosynthetic rate, transpiration, stomatal conductance, intercellular carbon dioxide concentration) under salt stress. We established 4 treatment groups and one control group based on salinity levels of NaCl hydroponic solutions (171, 342, 513, and 684 mm). The Na+/K+, Na+/Ca2+, chlorophyll fluorescence, and photosynthetic parameters of leaves were measured on the 1st, 3rd, 5th, 8th, 11th, and 15th days to analyze the correlations of chlorophyll, chlorophyll fluorescence and photosynthetic parameters to the ion distribution ratio. The results showed that (1) The ratio of the dry weight of roots to leaves gradually increased with increasing salt concentration, whereas the water content of leaves and roots first increased and then decreased with increasing time. (2) The content of Na+, Na+/K+, and Na+/Ca2+ in roots and leaves increased with increasing salt stress concentration and treatment time, and the difference gradually narrowed. (3) Ca2+ was lost more than K+ under salt stress, and Na+/Ca2+ was more sensitive to the salt stress environment than Na+/K+. (4) Because the root system had a retention effect, both Na+/K+ and Na+/Ca2+ in roots under different NaCl concentrations and different treatment times were higher than those in leaves, and Na+/Ca2+ was much higher than Na+/K+ in roots. (5) Na+/K+ had a higher correlation with fluorescence parameters than Na+/Ca2+. Among them, Na+/K+ had a significantly negative correlation with the maximum photochemical efficiency, and the correlation coefficient R2 was 0.8576. (6) Photosynthetic gas parameters had a higher correlation with Na+/Ca2+ than with Na+/K+. Among them, significantly negative correlations were noted between Na+/Ca2+ and Gs as well as between Na+/Ca2+ and E under salt stress. The correlation between Na+/Ca2+ and Gs was the highest with a correlation coefficient of 0.9368. (7) Na+/K+ and Na+/Ca2+ had no significant correlation with chlorophylls. Na+/Ca2+ was selected as a key index to evaluate the salt tolerance of S. matsudana Koidz, and the results provided a reference for analyzing the relationship between ion transport and distribution for photosynthesis.
Genome-Wide Identification of Wild Soybean Mitochondrial Calcium Uniporter Family Genes and Their Responses to Cold and Carbonate Alkaline Stresses
Authors: Li Jianwei , Sun Mingzhe , Liu Yu , Sun Xiaoli , Yin Kuide
Published: May 2022

The mitochondrial calcium uniporter (MCU), as an important component of the Ca2+ channel uniporter complex, plays a regulatory role in intracellular Ca2+ signal transduction. However, only a few studies to date have investigated plant MCU genes. In this study, we identified the MCU family genes in wild soybean and investigated their expression under cold and carbonate alkaline stresses. Eleven Glycine soja MCU genes (GsMCUs) were identified and clustered into two subgroups (subgroups I and II), and subgroup II could be further divided into two branches (MCU5 and MCU6). A total of 21 pairs of GsMCUs were characterized as duplicated genes, and displayed a similar exon-intron architecture. All GsMCU proteins contained one conserved MCU domain, within which two transmembrane domains were found. An analysis of the conserved motifs further supported that the GsMCUs showed high conservation in protein sequence and structure. Moreover, we found that all GsMCUs were expressed ubiquitously in different tissues and organs, and GsMCUs from the same subgroup displayed varied tissue expression profiles. In addition, based on RNA-seq and qRT-PCR assays, six and nine GsMCUs were differentially expressed under cold and carbonate alkaline stress, respectively. Promoter analysis also uncovered the existence of two canonical cold-related cis-acting elements, LTR and DRE/CRT, as well as stress-related phytohormone-responsive elements. Our results provide valuable information about the MCU family in soybean responses to cold and carbonate alkaline stress, which will be helpful in further characterizing their biological roles in response to abiotic stress.
Cotton miR393-TIR1 Module Regulates Plant Defense Against Verticillium dahliae via Auxin Perception and Signaling
Authors: Shi Gege , Wang Saisai , Wang Peng , Zhan Jingjing , Tang Ye , Zhao Ge , Li Fuguang , Ge Xiaoyang , Wu Jiahe
Published: May 2022

Plant auxin is essential in plant growth and development. However, the molecular mechanisms of auxin involvement in plant immunity are unclear. Here, we addressed the function of the cotton (Gossypium hirsutum) miR393-TIR1 module in plant defense against Verticillium dahliae infection via auxin perception and signaling. GhTIR1 was directedly cleaved by ghr-miR393 according to mRNA degradome data, 5′-RACE analysis, and a GUS reporter assay. Ghr-miR393 knockdown significantly increased plant susceptibility to V. dahliae compared to the control, while ghr-miR393 overexpression and GhTIR1 knockdown significantly increased plant resistance. External indole-3-acetic acid (IAA) application significantly enhanced susceptibility to V. dahliae in ghr-miR393 knockdown and control plants compared to mock treatment, and only slightly increased susceptibility in overexpressing ghr-miR393 and GhTIR1-silenced plants. Application of external PEO-IAA (an auxin antagonist) had a contrary trend with IAA application. Based on yeast two-hybrid and bimolecular fluorescence complementation assays, GhTIR1 interacted with GhIAA14 in the nucleus, and GhIAA14 knockdown reduced plant resistance to V. dahliae infection. The results suggested that the ghr-miR393-GhTIR1 module regulates plant defense via auxin perception and signaling. Additionally, simultaneous knockdown of GhTIR1 and GhICS1 significantly increased plant susceptibility to V. dahliae compared to the control, indicating that salicylic acid (SA) accumulation is vital for the ghr-miR393-GhTIR1 module to regulates plant resistance. Transcriptome data also demonstrated that GhTIR1 knockdown significantly downregulated expression of auxin-related genes and upregulated expression of SA-related genes. Overall, the ghr-miR393-GhTIR1 module participates in plant response to V. dahliae infection via IAA perception and signaling partially depending on the SA defense pathway.
Genetic Incorporation of the Favorable Alleles for Three Genes Associated With Spikelet Development in Wheat
Authors: Zhang Xiaojun , Qiao Linyi , Li Xin , Yang Zujun , Liu Cheng , Guo Huijuan , Zheng Jun , Zhang Shuwei , Chang Lifang , Chen Fang , Jia Juqing , Yan Liuling , Chang Zhijian
Published: May 2022

The number of spikelets per spike is an important trait that directly affects grain yield in wheat. Three quantitative trait loci (QTLs) associated with spikelet nodes per spike (SNS) were mapped in a population of recombinant inbred lines generated from a cross between two advanced breeding lines of winter wheat based on the phenotypic variation evaluated over six locations/years. Two of the three QTLs are QSns.sxau-2A at the WHEATFRIZZY PANICLE (WFZP) loci and QSns.sxau-7A at the WHEAT ORTHOLOG OF APO1 (WAPO1) loci. The WFZP-A1b allele with a 14-bp deletion at QSns.sxau-2A was associated with increased spikelets per spike. WAPO-A1e, as a novel allele at WAPO1, were regulated at the transcript level that was associated with the SNS trait. The third SNS QTL, QSns.sxau-7D on chromosome 7D, was not associated with homoeologous WAPO-D1 or any other genes known to regulate SNS. The favorable alleles for each of WZFP-A1, WAPO-A1, and QSns.sxau-7D are identified and incorporated to increase up to 3.4 spikelets per spike in the RIL lines. Molecular markers for the alleles were developed. This study has advanced our understanding of the genetic basis of natural variation in spikelet development in wheat.
Genome-Wide Identification and Expression of FAR1 Gene Family Provide Insight Into Pod Development in Peanut (Arachis hypogaea)
Authors: Lu Qing , Liu Hao , Hong Yanbin , Liang Xuanqiang , Li Shaoxiong , Liu Haiyan , Li Haifen , Wang Runfeng , Deng Quanqing , Jiang Huifang , Varshney Rajeev K. , Pandey Manish K. , Chen Xiaoping
Published: May 2022

The far-red-impaired response 1 (FAR1) transcription family were initially identified as important factors for phytochrome A (phyA)-mediated far-red light signaling in Arabidopsis; they play crucial roles in controlling the growth and development of plants. The reported reference genome sequences of Arachis, including A. duranensis, A. ipaensis, A. monticola, and A. hypogaea, and its related species Glycine max provide an opportunity to systematically perform a genome-wide identification of FAR1 homologous genes and investigate expression patterns of these members in peanut species. Here, a total of 650 FAR1 genes were identified from four Aarchis and its closely related species G. max. Of the studied species, A. hypogaea contained the most (246) AhFAR1 genes, which can be classified into three subgroups based on phylogenic relationships. The synonymous (Ks) and non-synonymous (Ka) substitution rates, phylogenetic relationship and synteny analysis of the FAR1 family provided deep insight into polyploidization, evolution and domestication of peanut AhFAR1 genes. The transcriptome data showed that the AhFAR1 genes exhibited distinct tissue- and stage-specific expression patterns in peanut. Three candidate genes including Ahy_A10g049543, Ahy_A06g026579, and Ahy_A10g048401, specifically expressed in peg and pod, might participate in pod development in the peanut. The quantitative real-time PCR (qRT-PCR) analyses confirmed that the three selected genes were highly and specifically expressed in the peg and pod. This study systematically analyzed gene structure, evolutionary characteristics and expression patterns of FAR1 gene family, which will provide a foundation for the study of genetic and biological function in the future.
Exploring the Influence of Failure Aversion on Learning From Project Failure: A Sensemaking Perspective
Authors: Zhang Liangting , Wang Bin , Feng Xiaoxia , Zhang Yue , Wang Wenzhou
Published: May 2022

Although project failure is commonly considered a negative event, it can provide valuable resources for learning. Despite well documented research on the antecedents of learning from project failure at the individual level, individuals’ attitude toward failures, a relatively proximal antecedent of learning from failure, has attracted limited attention in organizational studies. To address this paucity of research, based on the sensemaking theory, in the current study we specifically focused on individuals’ failure aversion and explored how it would influence learning from failure through the process of arguing and expectation. Using a sample of 774 employees from R&D teams in China, our findings revealed that individuals’ failure aversion enhanced their learning from failure through inducing a loss-focused coping, but failure aversion negatively affected learning from failure through increasing the individuals’ perceived loss of self-esteem. We also found that individuals’ learning goal orientation (LGO) weakened the negative relationship between the loss of self-esteem and learning from failure; however, LGO did not moderate our hypothesized relationship between loss-focused coping and learning from failure. Our study extends the literature on learning from failure in two ways. First, it explores the learning from failure process at the individual level based on the sensemaking theory and second, it sheds light on the underlying cognitive mechanisms operating between failure aversion and learning from project failure.
Classroom Seat Proximity Predicts Friendship Formation
Authors: Faur Sharon , Laursen Brett
Published: May 2022

The present study tests the hypothesis that friendships form on the basis of classroom seating proximity. Participants included 235 students (129 boys, 106 girls) in grades 3–5 (ages 8–11) who nominated friends at two time points (13–14 weeks apart). Teachers described seating arrangements. Concurrent analyses indicated that students sitting next to or nearby one another were more likely to receive friend nominations and be involved in reciprocated friendships than students seated elsewhere in the classroom. Longitudinal analyses indicated that classroom seating proximity was associated with the formation of new friendships. Most results for randomly selected outgoing friend nominations and randomly selected reciprocated friend dyads were replicated in analyses that included all friend nominations and all friend dyads.