Weather and Random Forest-based Load Profiling Approximation Models and Their Transferability across Climate Zones

This study is to provide predictive understanding of the associations of weather attributes with electricity load profiles across a variety of climate zones and seasons. Firstly, machine learning (ML) approaches were used to identify and quantify the impacts of various weather attributes on residential and commercial electricity demand and its components across the western United States. Performance and transferability of the developed ML models were then evaluated across different temperate zones (e.g., southern, middle, and northern US) and across coastal, mid-continent, and wet zones, with inputs of weather condition data from the National Oceanic and Atmospheric Administration (NOAA) at representative weather stations. The predictive models were developed based on the ranked and screened factors using the regression tree (RT) and random forest (RF) approaches, for five different scenarios (seasons)

Correlative study on retinal microvascular changes and sex hormones in male patients with central serous chorioretinopathy

Central serous chorioretinopathy (CSC) is a disease in which the outer retinal barrier is damaged with high incidence in young adult males. We aimed to analyze the correlations between retinal microvascular changes and sex hormone levels. The vascular density of the superficial retinal capillary plexus (SCP), deep retinal capillary plexus (DCP), foveal avascular zone (FAZ) area, choriocapillary blood flow area, and the subfoveal choroidal thickness (SCT) were investigated by optical coherence tomography angiography (OCTA). We also determined the levels of sex hormones (adrenaline (AD), norepinephrine (NE), dopamine (DA), corticosteroids (Cor), aldosterone (ALD), estradiol (E2) and total testosterone (TT)). The relationship between sex hormone levels and OCTA parameters was then determined. We detected significantly higher levels of NE, Cor and TT in serum from the observation group than in the control group (p < 0.05). Significant correlations were identified between SCT and choriocapillary blood flow area in the affected eyes, contralateral eyes and healthy eyes in the control group (p < 0.05). SCT levels of both eyes in the observation group were higher and the choriocapillary blood flow area was smaller than in the control group. The SCT in affected eyes from the observation group were higher than the contralateral eyes (p < 0.05). The choriocapillary blood flow area was significantly smaller than in the contralateral eyes (p < 0.05). Correlation analysis unveiled that NE, Cor and TT levels were positively correlated with SCT in CSC patients and negatively correlated with choriocapillary blood flow area (p < 0.05). The serum levels of sex hormone levels in male CSC patients were different from those in healthy men of the same age. Our findings suggest that the serum levels of NE, Cor and TT levels may influence the pathogenesis of CSC by affecting SCT thickness and choriocapillary blood flow

Effects of Active Components of Fuzi and Gancao Compatibility on Bax, Bcl-2, and Caspase-3 in Chronic Heart Failure Rats

Hypaconitine (HA) and glycyrrhetinic acid (GA) are active components of Fuzi (Aconitum carmichaelii) and Gancao (Glycyrrhiza uralensis Fisch); they have been used in compatibility for chronic heart failure (CHF) from ancient times. The purpose of the present research was to explore whether apoptosis pathways were related with the protective effects of HA + GA against CHF rats or not. The rats were progressed with transverse-aortic constriction (TAC) operation for 4 weeks to build the CHF state, and then the Digoxin (1 mg/kg), HA (2.07 mg/kg), GA (25 mg/kg), and HA (2.07 mg/kg) + GA (25 mg/kg) were orally administrated to rats for 1 week. The levels of BNP and cTnI in the plasma were decreased in the HA + GA group, and the heart/body weight ratio (H/B) and left ventricular (LV) parameters of transthoracic echocardiography were also declined; moreover, the expressions of Bax, Bcl-2, and caspase-3 were all improved in the HA + GA group than other groups in the immunohistochemistry and western blot methods. In general, the data suggested that Fuzi and Gancao compatibility could protect the CHF rats from apoptosis, which provided a strong evidence for further searching for mechanisms of them

Functional and structural analysis of a novel splice site HMBS variant in a Chinese AIP patient

Background: Acute intermittent porphyria (AIP) is a rare metabolic disorder that results from mutations in the gene encoding hydroxymethylbilane synthase (HMBS), an enzyme involved in heme biosynthesis. AIP follows an autosomal dominant inheritance pattern, but most carriers are asymptomatic. The clinical manifestations of AIP include acute attacks of abdominal pain and neuropsychiatric disturbances. The pathogenicity of novel HMBS variants identified in Chinese patients has not been well established.Objective: The article aims to identify the pathogenic mutation in an AIP patient and prove its pathogenicity through in vitro experiments.Methods: A 22-year-old female diagnosed with AIP participated in the study. Variant screening of her HMBS gene was carried out through Sanger sequencing. To ascertain the consequences of the newly discovered variant, we conducted in vitro experimentation targeting HMBS gene expression and enzymatic function. Additionally, protein structure analysis was performed. Cycloheximide treatment and UPF1-specific siRNA knockdown were employed to assess the impact of the mutation on the mechanism of non-sense-mediated mRNA decay (NMD).Results: A novel splice site variant in the HMBS gene (c.648_651+1delCCAGG) was detected in the patient, which caused aberrant mRNA splicing. In vitro experiments demonstrated that this variant significantly decreased the expression of HMBS. Further investigation confirmed that this decrease was due to NMD. Additionally, structural analysis indicated that this variant would destabilize the HMBS protein and impair its catalytic activity. To gain a comprehensive understanding of HMBS mutations in the context of AIP, we conducted a literature search on PubMed using the keywords ‘HMBS’ and ‘Acute intermittent porphyria’ from 2013 to 2023. This search yielded 19 clinical case reports written in English, which collectively described 220 HMBS gene mutations worldwide.Conclusion: The study identified and proved the pathogenicity of a novel splice site HMBS variant for the first time. Our results elucidated the pathological mechanism by which this mutation causes AIP through reducing HMBS expression and activity. These findings provide theoretical guidance for the diagnosis, treatment and genetic counseling of AIP patients

Circulating plasma and exosome levels of the miR-320 family as a non-invasive biomarker for methamphetamine use disorder

The neurobiological mechanism underlying methamphetamine (MA) use disorder was still unclear, and no specific biomarker exists for clinical diagnosis of this disorder. Recent studies have demonstrated that microRNAs (miRNAs) are involved in the pathological process of MA addiction. The purpose of this study was to identify novel miRNAs for the diagnosis biomarkers of MA user disorder. First, members of the miR-320 family, including miR-320a-3p, miR-320b, and miR-320c, were screened and analyzed in the circulating plasma and exosomes by microarray and sequencing. Secondly, plasma miR-320 was quantified by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) in eighty-two MA patients and fifty age-gender-matched healthy controls. Meanwhile, we also analyzed exosomal miR-320 expression in thirty-nine MA patients and twenty-one age-matched healthy controls. Furthermore, the diagnostic power was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. The expression of miR-320 significantly increased in plasma and exosomes of MA patients compared with healthy controls. The AUC of the ROC curves of miR-320 in plasma and exosomes of MA patients were 0.751 and 0.962, respectively. And the sensitivities of miR-320 were 0.900 and 0.846, respectively, whereas the specificities of miR-320 were 0.537 and 0.952, respectively, in plasma and exosomes in MA patients. And the increased plasma miR-320 was positively correlated with cigarette smoking, age of onset, and daily use of MA in MA patients. Finally, cardiovascular disease, synaptic plasticity, and neuroinflammation were predicted to be the target pathways related to miR-320. Taken together, our findings indicated that plasma and exosomal miR-320 might be used as a potential blood-based biomarker for diagnosing MA use disorder

Divergent nitrogen and phosphorus allocation strategies in terrestrial plant leaves and fine roots: a global meta-analysis

1. The quantification of the allocation of nitrogen (N) and phosphorus (P) among plant organs is essential to improve our understanding of plant growth, life-history strategies, and ecosystem nutrient and energy cycles. However, allocation strategies of N and P between terrestrial plant leaves and fine roots are unclear. 2. Here, we compiled a global dataset comprising 807 terrestrial plant species to analyze the stoichiometric scaling of N and P between leaves and fine roots across species, families, plant groups, biomes, and locations. 3. We found that N and P, and N:P ratios manifest different scaling exponents (α-values) between leaves and fine roots. Specifically, overall αN and αP were >1 and <1, respectively, and αN:P = 1, indicating a higher proportional increase of N to fine roots and P to leaves. However, there were differences in αN, αP, and αN:P among major species, families, plant groups, biomes, and locations. In addition, αN and αN:P increased with latitude; there was no clear trend for αP. Mean annual temperature accounted for the greatest proportion of variation in αN, whereas soil total P accounted for the greatest proportion of variation in αP and αN:P. 4. Synthesis. Our results demonstrate a divergent N and P allocation strategy between leaves and fine roots in terrestrial plants. This study improves our understanding of the effects of the environment (including changes in global climate, and life history strategies) on nutrient allocation patterns between these two important plant organs.This work was funded by the European Research Council Synergy project SyG-2013-610028 IMBALANCE-P, the Catalan Government grants AGAUR-2020PANDE00117 and SGR 2017-1005, the Spanish Government grant PID2019-110521GB-I00, the Fundac ió n Ra mó n A reces gr a nt ELEMEN TA L-CLIM ATE, t he N at io na l Sc ie nc e Fund for Excellent Young Scholars (31822010), the B iod iver s it y Sur ve y a nd A ssess me nt Pro ject o f t he M inis tr y o f Ecology and Environment, C hina (2019HJ2096001006), National Scientific and Technological Program on Basic Resources Investigation (2019FY102002) and the Innovation Base Project of Gansu Province (20190323).Peer reviewe

Genetic polymorphisms of MDM2 and TP53 genes are associated with risk of nasopharyngeal carcinoma in a Chinese population

<p>Abstract</p> <p>Background</p> <p>The tumor suppressor TP53 and its negative regulator MDM2 play crucial roles in carcinogenesis. Previous case-control studies also revealed <it>TP53 </it>72Arg>Pro and <it>MDM2 </it>309T>G polymorphisms contribute to the risk of common cancers. However, the relationship between these two functional polymorphisms and nasopharyngeal carcinoma (NPC) susceptibility has not been explored.</p> <p>Methods</p> <p>In this study, we performed a case-control study between 522 NPC patients and 722 healthy controls in a Chinese population by using PCR-RFLP.</p> <p>Results</p> <p>We found an increased NPC risk associated with the <it>MDM2 </it>GG (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 2.08-3.96) and TG (OR = 1.49, 95% CI = 1.16-2.06) genotypes. An increased risk was also associated with the <it>TP53 </it>Pro/Pro genotype (OR = 2.22, 95% CI = 1.58-3.10) compared to the Arg/Arg genotype. The gene-gene interaction of <it>MDM2 </it>and <it>TP53 </it>polymorphisms increased adult NPC risk in a more than multiplicative manner (OR for the presence of both <it>MDM2 </it>GG and <it>TP53 </it>Pro/Pro genotypes = 7.75, 95% CI = 3.53-17.58).</p> <p>Conclusion</p> <p>The findings suggest that polymorphisms of <it>MDM2 </it>and <it>TP53 </it>genes may be genetic modifier for developing NPC.</p

Single nucleus genome sequencing reveals high similarity among nuclei of an endomycorrhizal fungus

Nuclei of arbuscular endomycorrhizal fungi have been described as highly diverse due to their asexual nature and absence of a single cell stage with only one nucleus. This has raised fundamental questions concerning speciation, selection and transmission of the genetic make-up to next generations. Although this concept has become textbook knowledge, it is only based on studying a few loci, including 45S rDNA. To provide a more comprehensive insight into the genetic makeup of arbuscular endomycorrhizal fungi, we applied de novo genome sequencing of individual nuclei of Rhizophagus irregularis. This revealed a surprisingly low level of polymorphism between nuclei. In contrast, within a nucleus, the 45S rDNA repeat unit turned out to be highly diverged. This finding demystifies a long-lasting hypothesis on the complex genetic makeup of arbuscular endomycorrhizal fungi. Subsequent genome assembly resulted in the first draft reference genome sequence of an arbuscular endomycorrhizal fungus. Its length is 141 Mbps, representing over 27,000 protein-coding gene models. We used the genomic sequence to reinvestigate the phylogenetic relationships of Rhizophagus irregularis with other fungal phyla. This unambiguously demonstrated that Glomeromycota are more closely related to Mucoromycotina than to its postulated sister Dikarya