Adaptive foraging behaviours in the Horn of Africa during Toba supereruption.

Although modern humans left Africa multiple times over 100,000 years ago, those broadly ancestral to non-Africans dispersed less than 100,000 years ago1. Most models hold that these events occurred through green corridors created during humid periods because arid intervals constrained population movements2. Here we report an archaeological site-Shinfa-Metema 1, in the lowlands of northwest Ethiopia, with Youngest Toba Tuff cryptotephra dated to around 74,000 years ago-that provides early and rare evidence of intensive riverine-based foraging aided by the likely adoption of the bow and arrow. The diet included a wide range of terrestrial and aquatic animals. Stable oxygen isotopes from fossil mammal teeth and ostrich eggshell show that the site was occupied during a period of high seasonal aridity. The unusual abundance of fish suggests that capture occurred in the ever smaller and shallower waterholes of a seasonal river during a long dry season, revealing flexible adaptations to challenging climatic conditions during the Middle Stone Age. Adaptive foraging along dry-season waterholes would have transformed seasonal rivers into 'blue highway' corridors, potentially facilitating an out-of-Africa dispersal and suggesting that the event was not restricted to times of humid climates. The behavioural flexibility required to survive seasonally arid conditions in general, and the apparent short-term effects of the Toba supereruption in particular were probably key to the most recent dispersal and subsequent worldwide expansion of modern humans.

Comprehensive profiling of epigenetic modifications in fast-growing Moso bamboo shoots.

The fast growth of Moso bamboo (Phyllostachys edulis) shoots is caused by the rapid elongation of each internode. However, the key underlying cellular processes and epigenetic mechanisms remain largely unexplored. We used microscopy and multi-omics approaches to investigate two regions (bottom and middle) of the 18th internode from shoots of two different heights (2 and 4 m). We observed that internode cells become longer, and that lignin biosynthesis and glycosyltransferase family 43 (GT43) genes are substantially upregulated with shoot height. Nanopore direct RNA sequencing (DRS) revealed a higher N6-methyladenine (m6A) modification rate in 2-m shoots than in 4-m shoots. In addition, different specific m6A modification sites were enriched at different growth stages. Global DNA methylation profiling indicated that DNA methylation levels are higher in 4-m shoots than in 2-m shoots. We also detected shorter poly(A) tail lengths (PALs) in 4-m shoots compared with 2-m shoots. Genes showing differential PAL were mainly enriched in the functional terms of protein translation and vesicle fusion. An association analysis between PALs and DNA methylation strongly suggested that gene body CG methylation levels are positively associated with PAL. This study provides valuable information to better understand post-transcriptional regulations responsible for fast-growing shoots in Moso bamboo.

Congenital trans-sellar trans-sphenoidal encephalocele: a systematic review of diagnosis, treatment, and prognosis.

PURPOSE: Clinical presentations encompass respiratory, feeding issues, nasopharyngeal mass, meningitis, CSF leakage, craniofacial anomalies, and endocrine problems. Surgery is the primary treatment, transitioning from frontal craniotomy to endoscopic methods, offering improved outcomes. Yet, more studies are needed. A comprehensive review on trans-sellar trans-sphenoidal encephalocele (TSTSE) is missing. Our study aims to fill this gap, offering a comprehensive perspective for physicians. METHODS: This review adhered to the PRISMA guideline. Eligible studies focused on human subjects, specifically trans-sellar encephaloceles, and provided comprehensive treatment details. English language articles published up to April 11th, 2023, were considered. Two trained researchers conducted article screening using consistent criteria. Data extraction covered various aspects, including clinical presentation, surgical methods, and outcomes, with results presented descriptively in two tables. Due to the rarity of this congenital anomaly, meta-analysis and publication bias assessment were not feasible. Data extraction was independently conducted by two reviewers, with subsequent cross-verification. RESULTS: A total of 36 patients were identified from 14 studies, the most frequently observed clinical presentation was dyspnea (41.67%) and the most frequently observed accompanying anomaly was cleft lip/palate (55.56%). CT and MRI were adopted in nearly all the cases, and trans-nasal approach was the most often used surgical approach (57.14%) with the 'soft material combination' the most commonly used method for cranial base repairment (35.71%). A total of two deaths occurred and diabetes insipidus was the most common perioperative complication which occurred in six surgery patients (21.43%). CONCLUSION: TSTSE predominantly affects males and presents with dyspnea, visual deficits, pituitary insufficiency, and cranial base-related symptoms. Early diagnosis is critical, with advanced imaging playing a key role. Endocrine assessment is vital for hormone management. Surgery offers symptom relief but entails risks, including reported fatalities and complications. The choice between surgery and conservative management requires careful deliberation. The trans-nasal approach is favored for its reduced trauma, yet further research is necessary to validate this preference.

Study on the Effect of Petroleum Components on the Elution of Oily Sludge by a Compound Biosurfactant.

Currently, research on oily sludge treatment mainly focuses on optimizing the deoiling effect and research on the deoiling mechanism, and the influence of petroleum components on the properties and treatment of oily sludge is rarely considered. Therefore, in this study, petroleum substances in three types of oil sludge were eluted using the biosurfactant cleaning technology, and the influence of petroleum components on the cleaning process was explored. The results showed that the biosurfactants rhamnolipid and sophorolipid had a synergistic effect, and the oil-removal rate was as high as 92.2% when the SL mass fraction was 0.4 in the compound biosurfactant. Three types of oily sludge, wellsite-landing sludge, pipeline-landing sludge, and tank-bottom sludge, were cleaned by the compound biosurfactant; the results showed that the residual petroleum substance in liquid and solid phases, the turbidity value, and the zeta-potential value of the supernatant of oil sludge samples after cleaning increased with the increase in the heavy components of the oily sludge, and the oil-removal rate decreased gradually. After cleaning, the average relative molecular weight of the three oil phases increased with the heavy components, which was increased by 1.83, 4.83, and 10.72%, respectively, and the increase in molecular weight increased the difficulty of cleaning. After cleaning, the retention time and peak intensity of the oil sample changed significantly, and it had a stronger elution effect on low-molecular-weight alkanes. It was found that the compound biosurfactant had a good elution effect on polycyclic aromatic hydrocarbons, but the increase in the content of heavy components and the increase in aromatic rings increased the difficulty of cleaning. Moreover, it was found that the compound biosurfactant could not completely elute the petroleum substances on the surface of solid particles, and the asphaltene components in the oil phase were more difficult to elute than other components.

Genome-Wide Identification of NAP1 and Function Analysis in Moso Bamboo (Phyllostachys edulis).

The nucleosome assembly protein 1 (NAP1) family is the main histone chaperone of histone H2A-H2B. To explore the function of NAP1 family genes in moso bamboo (Phyllostachys edulis), characterized by extremely rapid growth and a long flowering cycle, we originally conducted a genome-wide analysis of the PheNAP1 gene. The phylogenetic relationship, gene expression pattern, DNA methylation, and histone modification were analyzed. Eventually, 12 PheNAP1 genes were recognized from the Phyllostachys edulis genome, divided into two sorts: the NRP subfamily (four members) and the NAP subfamily (eight members). Highly conserved motifs exist in each subfamily, which are distinct between subfamilies. PheNAP1 was distributed homogeneously on 10 out of 24 chromosomes, and gene duplication contributed significantly to the enhancement of the PheNAP1 gene in the genome. Cis-acting element analysis showed that PheNAP1 family genes are involved in light, hormone, and abiotic stress responses and may play an important role in the rapid growth and flowering. PheNAP1 exhibited the highest expression level in fast-growing shoots, indicating it is closely associated with the rapid growth of moso bamboo. Besides, PheNAP1 can rescue the early-flowering phenotype of nrp1-1 nrp2-2, and it affected the expression of genes related to the flowering pathway, like BSU1, suggesting the vital role that PheNAP1 may take in the flowering process of moso bamboo. In addition, histone modification results showed that PheNAP1 could bind to phosphorylation-, acetylation-, and methylation-modified histones to further regulate gene expression. A sketch appears: that PheNAP1 can accompany histones to regulate fast-growth- and flowering-related genes in moso bamboo. The consequences of this study enrich the understanding of the epigenetic regulation mechanism of bamboo plants and lays a foundation for further studies on the role of the NAP1 gene in Phyllostachys edulis and the function of chromatin regulation in forest growth and development.

Nitric Oxide Mobilizes Intracellular Zn2+ via the GC/cGMP/PKG Signaling Pathway and Stimulates Adipocyte Differentiation.

Plasma and tissue zinc ion levels are associated with the development of obesity. Previous studies have suggested that zinc ions may regulate adipocyte metabolism and that nitric oxide (NO) plays a pivotal role in the regulation of adipocyte physiology. Our previous study showed that chronic NO deficiency causes a significant decrease in adipose tissue mass in rats. Studies also suggested that zinc ions play an important modulatory role in regulating NO function. This study aims to explore the role of zinc ions in NO-regulated adipocyte differentiation. We hypothesized that NO could increase intracellular Zn2+ level and then stimulate adipocyte differentiation. ZnCl2 and the NO donor, NONOate, were used to explore the effects of Zn2+ and NO on adipocyte differentiation. Regulatory mechanisms of NO on intracellular Zn2+ mobilization were determined by detection. Then, Zn2+-selective chelator TPEN was used to clarify the role of intracellular Zn2+ on NO-regulated adipocyte differentiation. Furthermore, the relationship between adipocyte size, Zn2+ level, and NOS expression in human subcutaneous fat tissue was elucidated. Results showed that both ZnCl2 and NO stimulated adipocyte differentiation in a dose-dependent manner. NO stimulated intracellular Zn2+ mobilization in adipocytes through the guanylate cyclase (GC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) pathway, and NO-stimulated adipocyte differentiation was Zn2+-dependent. In human subcutaneous adipose tissue, adipocyte size was negatively correlated with expression of eNOS. In conclusion, NO treatment stimulates intracellular Zn2+ mobilization through the GC/cGMP/PKG pathway, subsequently stimulating adipocyte differentiation.

Allele-aware chromosome-scale assembly of the allopolyploid genome of hexaploid Ma bamboo (Dendrocalamus latiflorus Munro).

Dendrocalamus latiflorus Munro is a woody clumping bamboo with rapid shoot growth. Both genetic transformation and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing techniques are available for D. latiflorus, enabling reverse genetic approaches. Thus, D. latiflorus has the potential to be a model bamboo species. However, the genome sequence of D. latiflorus has remained unreported due to its polyploidy and large genome size. Here, we sequenced the D. latiflorus genome and assembled it into three allele-aware subgenomes (AABBCC), representing the largest genome of a major bamboo species. We assembled 70 allelic chromosomes (2, 737 Mb) for hexaploid D. latiflorus using both single-molecule sequencing from the Pacific Biosciences (PacBio) Sequel platform and chromosome conformation capture sequencing (Hi-C). Repetitive sequences comprised 52.65% of the D. latiflorus genome. We annotated 135 231 protein-coding genes in the genome based on transcriptomes from eight different tissues. Transcriptome sequencing using RNA-Seq and PacBio single-molecule real-time long-read isoform sequencing revealed highly differential alternative splicing (AS) between non-abortive and abortive shoots, suggesting that AS regulates the abortion rate of bamboo shoots. This high-quality hexaploid genome and comprehensive strand-specific transcriptome datasets for this Poaceae family member will pave the way for bamboo research using D. latiflorus as a model species.

Consequences of LED Lights on Root Morphological Traits and Compounds Accumulation in Sarcandra glabra Seedlings.

This study evaluated the effects of different light spectra (white light; WL, blue light; BL and red light; RL) on the root morphological traits and metabolites accumulation and biosynthesis in Sarcandra glabra. We performed transcriptomic and metabolomic profiling by RNA-seq and ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS), respectively. When morphological features were compared to WL, BL substantially increased under-ground fresh weight, root length, root surface area, and root volume, while RL inhibited these indices. A total of 433 metabolites were identified, of which 40, 18, and 68 compounds differentially accumulated in roots under WL (WG) vs. roots under BL (BG), WG vs. roots under RL (RG), and RG vs. BG, respectively. In addition, the contents of sinapyl alcohol, sinapic acid, fraxetin, and 6-methylcoumarin decreased significantly in BG and RG. In contrast, chlorogenic acid, rosmarinyl glucoside, quercitrin and quercetin were increased considerably in BG. Furthermore, the contents of eight terpenoids compounds significantly reduced in BG. Following transcriptomic profiling, several key genes related to biosynthesis of phenylpropanoid-derived and terpenoids metabolites were differentially expressed, such as caffeic acid 3-O-methyltransferase) (COMT), hydroxycinnamoyl-CoA shikimate hydroxycinnamoyl transferase (HCT), O-methyltransferase (OMT), and 1-deoxy-D-xylulose-5-phosphate synthetase (DXS). In summary, our findings showed that BL was suitable for growth and accumulation of bioactive metabolites in root tissue of S. glabra. Exposure to a higher ratio of BL might have the potential to improve the production and quality of S. glabra seedlings, but this needs to be confirmed further.

Transcriptomic and metabolomic profiling reveals the effect of LED light quality on morphological traits, and phenylpropanoid-derived compounds accumulation in Sarcandra glabra seedlings.

BACKGROUND: Sarcandra glabra is an evergreen and traditional Chinese herb with anti-oxidant, anti-bacterial, anti-inflammatory, and anti-tumor effects. Light is one of the most influential factor affecting the growth and quality of herbs. In recent times, the introduction of Light Emission Diode (LED) technology has been widely used for plants in greenhouse. However, the impact of such lights on plant growth and the regulatory mechanism of phenylpropanoid-derived compounds in S. glabra remain unclear. RESULTS: The red LED light (RL) substantially increased the plant height and decreased the stem diameter and leaf area relative to the white LED light (WL), while the blue LED light (BL) significantly reduced the height and leaf area of S. glabra. According to transcriptomic profiling, 861, 378, 47, 10,033, 7917, and 6379 differentially expressed genes (DEGs) were identified among the groups of leaf tissue under BL (BY) vs. leaf tissue under RL (RY), BY vs. leaf tissue under WL (WY), RY vs. WY, root tissue under WL (WG) vs. WY, stem tissue under WL (WJ) vs. WG, and WJ vs. WY, respectively. We identified 46 genes encoding for almost all known enzymes involved in phenylpropanoid biosynthesis, e.g., phenylalanine ammonia lyase (PAL), chalcone synthase (CHS), and flavonol synthase (FLS). We found 53 genes encoding R2R3-MYB proteins and bHLH proteins, respectively, where several were related to flavonoids biosynthesis. A total of 454 metabolites were identified based on metabolomic profiling, of which 44, 87, and 296 compounds were differentially produced in WY vs. RY, WY vs. BY, and WY vs. WG. In BY there was a substantial reduction in the production of esculetin, caffeic acid, isofraxidin, and fraxidin, while the yields of quercitrin and kaempferol were significantly up-regulated. In RY, the contents of cryptochlorogenic acid, cinnamic acid, and kaempferol decreased significantly. Besides, in WG, the production of metabolites (e.g. chlorogenic acid, cryptochlorogenic acid, and scopolin) declined, while their yields increased significantly (e.g. esculetin, fraxetin, isofraxidin, and fraxidin). CONCLUSION: These results provide further insight into the regulatory mechanism of accumulation patterns of phenylpropanoid-derived compounds in S. glabra under various light conditions, allowing optimum breeding conditions to be developed for this plant.

Monitoring the Heavy Metal Lead Inside Living Drosophila with a FRET-Based Biosensor.

The harmful impact of the heavy metal lead on human health has been known for years. However, materials that contain lead remain in the environment. Measuring the blood lead level (BLL) is the only way to officially evaluate the degree of exposure to lead. The so-called "safe value" of the BLL seems to unreliably represent the secure threshold for children. In general, lead's underlying toxicological mechanism remains unclear and needs to be elucidated. Therefore, we developed a novel genetically encoded fluorescence resonance energy transfer (FRET)-based lead biosensor, Met-lead, and applied it to transgenic Drosophila to perform further investigations. We combined Met-lead with the UAS-GAL4 system to the sensor protein specifically expressed within certain regions of fly brains. Using a suitable imaging platform, including a fast epifluorescent or confocal laser-scanning/two-photon microscope with high resolution, we recorded the changes in lead content inside fly brains ex vivo and in vivo and at different life stages. The blood-brain barrier was found to play an important role in the protection of neurons in the brain against damage due to the heavy metal lead, either through food or microinjection into the abdomen. Met-lead has the potential to be a powerful tool for the sensing of lead within living organisms by employing either a fast epi-FRET microscope or high-resolution brain imaging.

A Review of SARS-CoV-2 and the Ongoing Clinical Trials.

The sudden outbreak of 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) in Wuhan, China, which rapidly grew into a global pandemic, marked the third introduction of a virulent coronavirus into the human society, affecting not only the healthcare system, but also the global economy. Although our understanding of coronaviruses has undergone a huge leap after two precedents, the effective approaches to treatment and epidemiological control are still lacking. In this article, we present a succinct overview of the epidemiology, clinical features, and molecular characteristics of SARS-CoV-2. We summarize the current epidemiological and clinical data from the initial Wuhan studies, and emphasize several features of SARS-CoV-2, which differentiate it from SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), such as high variability of disease presentation. We systematize the current clinical trials that have been rapidly initiated after the outbreak of COVID-19 pandemic. Whereas the trials on SARS-CoV-2 genome-based specific vaccines and therapeutic antibodies are currently being tested, this solution is more long-term, as they require thorough testing of their safety. On the other hand, the repurposing of the existing therapeutic agents previously designed for other virus infections and pathologies happens to be the only practical approach as a rapid response measure to the emergent pandemic, as most of these agents have already been tested for their safety. These agents can be divided into two broad categories, those that can directly target the virus replication cycle, and those based on immunotherapy approaches either aimed to boost innate antiviral immune responses or alleviate damage induced by dysregulated inflammatory responses. The initial clinical studies revealed the promising therapeutic potential of several of such drugs, including favipiravir, a broad-spectrum antiviral drug that interferes with the viral replication, and hydroxychloroquine, the repurposed antimalarial drug that interferes with the virus endosomal entry pathway. We speculate that the current pandemic emergency will be a trigger for more systematic drug repurposing design approaches based on big data analysis.

Complete permanent mandibular dentition of early Homo from the upper Burgi Member of the Koobi Fora Formation, Ileret, Kenya.

The KNM-ER 64060 dentition derives from a horizon that most likely dates to between 2.02 and 2.03 Ma. A proximate series of postcranial bones (designated KNM-ER 64061) derives from the same siltstone unit and may be associated with the dentition, but their separation on the surface of the site leaves some room for doubt. KNM-ER 64060 is one of fewer than ten hominin specimens from the Early Pleistocene of East Africa that comprises a full or nearly complete mandibular dentition. Its taxonomic attribution is potentially significant, especially if the postcranial elements are related. At least three, and probably four hominin species, including Paranthropus boisei and Homo erectus (= H. ergaster), are known at about this time in East Africa. Other penecontemporaneous fossils have been referred to a single, highly variable species, H. habilis, or two taxa, namely H. habilis and H. rudolfensis. Although the weight of evidence supports the attribution of these specimens to two species, there is notable lack of agreement over the assignation of individual fossils. We take a conservative approach and group all such specimens under the designation "early Homo sp." for comparative purposes. KNM-ER 64060 is clearly attributable to Homo rather than Paranthropus. The preponderance of the evidence suggests that the affinities of KNM-ER 64060 are with fossils assigned to the early Homo sp. category rather than with H. erectus. This is indicated by the overall sizes of the KNM-ER 64060 canine, premolar and molar crowns, the size relationships of the P3 to P4, the relative narrowness of its premolar crowns, the cusp proportions of the M1 and especially those of the M2 and M3, and seemingly the possession of a two-rooted P4. Some of these comparisons suggest further that among the fossils comprising the early Homo sp. sample, the KNM-ER 64060 dentition exhibits greater overall similarity to specimens such as OH 7 and OH 16 that represent Homo habilis sensu stricto.

Evaluation of reference-scaled average bioequivalence of two oral formulations of abiraterone acetate in healthy Chinese subjects
.

OBJECTIVE: This study was designed to evaluate the pharmacokinetic (PK) properties and bioequivalence (BE) of two 250-mg tablet formulations of abiraterone acetate: a newly developed generic formulation (test) and a branded formulation (reference) in healthy adult Chinese subjects under fasted (n = 40) and fed (n = 40) conditions. MATERIALS AND METHODS: The comparison was performed using a single-dose, open, randomized, and four-way replicate study. The concentration of abiraterone in blood samples taken over 48 hours was determined by liquid chromatography tandem mass spectrometry (LC-MS/MS). To assess the BE of the test and reference formulations, confidence intervals (CI, 90%) for the peak plasma concentration (Cmax) and area under the concentration-time curves (AUC0-t and AUC0-∞) were calculated using the reference-scaled average bioequivalence (RSABE) method. RESULTS: The results showed that the 90% CIs for the ratios of Cmax, AUC0-t, and AUC0-∞ in the fasted study were 90.14 - 114.11, 93.96 - 115.07, and 93.72 - 113.331, respectively. For the fed study, the 90% CIs were 81.83 - 102.51, 91.51 - 104.89, and 91.46 - 104.58, respectively. CONCLUSION: In conclusion, the tested 250-mg abiraterone tablets were bioequivalent to 250-mg Zytiga tablets (reference) under both fasted and fed conditions. In addition, food intake increased the systemic exposure and Cmax of abiraterone by 3-fold and 7-fold, respectively.
.

Dopamine elevates intracellular zinc concentration in cultured rat embryonic cortical neurons through the cAMP-nitric oxide signaling cascade.

Zinc ion (Zn2+), the second most abundant transition metal after iron in the body, is essential for neuronal activity and also induces toxicity if the concentration is abnormally high. Our previous results show that exposure of cultured cortical neurons to dopamine elevates intracellular Zn2+ concentrations ([Zn2+]i) and induces autophagosome formation but the mechanism is not clear. In this study, we characterized the signaling pathway responsible for the dopamine-induced elevation of [Zn2+]i and the effect of [Zn2+]i in modulating the autophagy in cultured rat embryonic cortical neurons. N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), a membrane-permeable Zn2+ chelator, could rescue the cell death and suppress the autophagosome puncta number induced by dopamine. Dopamine treatment increased the lipidation level of the endogenous microtubule-associated protein 1A/1B-light chain 3 (LC3 II), an autophagosome marker. TPEN added 1h before, but not after, dopamine treatment suppressed the dopamine-induced elevation of LC3 II level. Inhibitors of the dopamine D1-like receptor, protein kinase A (PKA), and NOS suppressed the dopamine-induced elevation of [Zn2+]i. PKA activators and NO generators directly increased [Zn2+]i in cultured neurons. Through cell fractionation, proteins with m.w. values between 5 and 10kD were found to release Zn2+ following NO stimulation. In addition, TPEN pretreatment and an inhibitor against PKA could suppress the LC3 II level increased by NO and dopamine, respectively. Therefore, our results demonstrate that dopamine-induced elevation of [Zn2+]i is mediated by the D1-like receptor-PKA-NO pathway and is important in modulating the cell death and autophagy.

Molecular Characterization, Polymorphism, and Association of Porcine GADD45G Gene.

Growth arrest and DNA-damage-inducible gamma (GADD45G) is a reproduction related gene. In this study, the full-length cDNA sequence of porcine GADD45G gene was cloned through rapid amplification of cDNA ends (RACE) method. The porcine GADD45G gene encodes a protein of 159 amino acids that shares high homology with the GADD45G of nine species: chimpanzee (97%), sumatran orangutan (97%), white-tufted-ear marmoset (97%), northern white-cheeked gibbon (97%), cattle (97%), human (97%), rhesus monkey (97%), rat (96%), and mouse (95%). This novel porcine gene was assigned to GeneID: 100152997. Phylogenetic analysis revealed that the porcine GADD45G gene has a closer genetic relationship with the GADD45G gene of cattle. Computer-assisted analysis indicated that porcine GADD45G gene is structured in four exons and three introns. PCR-Rsa I-RFLP was established to detect an A/G mutation on the position of 294-bp of coding sequence and eight pig breeds display obvious genotype and allele frequency differences at this mutation locus. Association of this SNP with litter size traits was assessed in Large White (n = 100) and Landrace (n = 100) pig populations, and result demonstrated that this polymorphic locus was significantly associated with the litter size of all parities in Large White and Landrace sows (P < 0.01). Therefore, porcine GADD45G gene could be a useful candidate gene in selection for increasing the litter size. These data serve as a foundation for further insight into this novel porcine gene.

Structure-based approaches against COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has had a major impact on human life. This review highlights the versatile roles of both classical and modern structure-based approaches for COVID-19. X-ray crystallography, nuclear magnetic resonance spectroscopy, and cryogenic electron microscopy are the three cornerstones of classical structural biology. These technologies have helped provide fundamental and detailed knowledge regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the related human host proteins as well as enabled the identification of its target sites, facilitating the cessation of its transmission. Further progress into protein structure modeling was made using modern structure-based approaches derived from homology modeling and integrated with artificial intelligence (AI), facilitating advanced computational simulation tools to actively guide the design of new vaccines and the development of anti-SARS-CoV-2 drugs. This review presents the practical contributions and future directions of structure-based approaches for COVID-19.

Involvement of Rab3A in vesicle priming during exocytosis: interaction with Munc13-1 and Munc18-1.

Rab3A is a small G-protein of the Rab family that is involved in the late steps of exocytosis. Here, we studied the role of Rab3A and its relationship with Munc13-1 and Munc18-1 during vesicle priming. Phorbol 12-myristate 13-acetate (PMA) is known to enhance the percentage of fusion-competent vesicles and this is mediated by protein kinase C (PKC)-independent Munc13-1 activation and PKC-dependent dissociation of Munc18-1 from syntaxin 1a. Our results show that the effects of PMA varied in cells overexpressing Rab3A or mutants of Rab3A and in cells with Rab3A knockdown. When Munc13-1 was overexpressed in Rab3A knockdown cells, secretion was completely inhibited. In cells overexpressing a Rab-interacting molecule (RIM)-binding deficient Munc13-1 mutant, 128-Munc13-1, the effects of Rab3A on PMA-induced secretion was abolished. The effect of PMA, which disappeared in cells overexpressing GTP-Rab3A (Q81L), could be reversed by co-expressing Munc18-1 but not its mutant R39C, which is unable to bind to syntaxin 1a. In cells overexpressing Munc18-1, manipulation of Rab3A activity had no effect on secretion. Finally, Munc18-1 enhanced the dissociation of Rab3A, and such enhancement correlated with exocytosis. In summary, our results support the hypothesis that the Rab3A cycle is coupled with the activation of Munc13-1 via RIM, which accounts for the regulation of secretion by Rab3A. Munc18-1 acts downstream of Munc13-1/RIM/Rab3A and interacts with syntaxin 1a allowing vesicle priming. Furthermore, Munc18-1 promotes Rab3A dissociation from vesicles, which then results in fusion.

A mathematical model for supercooling process and its application to frazil ice evolution.

The calculation of the number of ice crystals for the model of frazil ice evolution is very important and affects the whole frazil events. In this paper, the general formula for the number of frazil ice crystals was established considering secondary nucleation, flocculation, gravity and turbulent entrainment, and ice crystals by melting. Meanwhile, two physical processes of secondary nucleation and flocculation were expressed by introducing critical impact velocity and the probability of flocculation from previous models. It has been found that the simulation results of frazil ice evolution are in good agreement with the experimental data and actual project. Then, Sobol method is carried out to judge parameters' influence degree, which found the number of nuclei produced [Formula: see text] is the most sensitive and has the greatest influence on the model results. In addition, sensitivity analysis of these parameters shows that they can affect the maximum supercooling and the period of supercooling. Therefore, the calculation method of the number of ice crystals is applied, which provides technical support for exploring the water temperature and internal relationship of frazil ice evolution.

Portable sensing devices for smart healthcare and prevention of lead poisoning.

Lead (Pb) poisoning can damage human bodies silently, without specific symptoms or conspicuous warning signs. To provide safe and user-friendly tools for detecting heavy metals at low concentrations, scientists have developed and optimized versatile biosensors. To practically employ the developed biosensors specific for Pb (eg, the optimized Met-lead 1.44 M1), smartphone applications designed for user convenience and are easily operable for the on-site detection of Pb in environmental water, drinking water, food, and blood/urine are urgently needed. To establish a monitoring system for home health maintenance, a portable device and useful apps installed on a smartphone can be integrated, and the data acquired can be sent to and stored in the cloud for further analysis and evidence preservation. With the high transmissions speeds for 4G and 4G wireless Internet, such a system can be applied for health protection; water-quality data can be provided by anyone and publicly shared for display on smartphone interfaces, alerting individuals of heavy metal contamination. In this review, we describe recent developments in heavy metal-sensing devices, including home health maintenance systems, which have been successfully and practically applied to prevent heavy metal Pb poisoning.

The role of transforming growth factor-ß2 in cigarette smoke-induced lung inflammation and injury.

AIMS: Transforming growth factor-ß2 (TGF-ß2) plays an important role in pleiotropic functions and has been reported to be involved in the pathogenesis of chronic obstructive lung disease. The role of TGF-ß2 in regulating cigarette smoke (CS)-induced lung inflammation and injury has not been investigated, and its underlying mechanism remains unclear. MAIN METHODS: Primary bronchial epithelial cells (PBECs) were treated with cigarette smoke extract (CSE), and the signaling pathway of TGF-ß2 regulating lung inflammation was investigated. Mice were exposed to CS and treated with TGF-ß2 i.p. or bovine whey protein extract containing TGF-ß2 p.o., and the role of TGF-ß2 in alleviating lung inflammation/injury was studied. KEY FINDINGS: In vitro, we demonstrated that TGF-ß2 attenuated CSE-induced IL-8 production from PBECs through the TGF-ß receptor I (TGF-ßRI), Smad3, and mitogen-activated protein kinase signaling pathways. Selective TGF-ßRI inhibitor (LY364947) and antagonist of Smad3 (SIS3) abolished the effect of TGF-ß2 on alleviating CSE-induced IL-8 production. In vivo, CS exposure for 4 weeks in mice increased the levels of total protein, inflammatory cell counts, and monocyte chemoattractant protein-1 in bronchoalveolar fluid and induced lung inflammation/injury, as revealed by immunohistochemistry. Administration of TGF-ß2 through intraperitoneal injection or oral feeding with bovine whey protein extract containing TGF-ß2 significantly reduced CS-induced lung inflammation and injury. SIGNIFICANCE: We concluded that TGF-ß2 reduced CSE-induced IL-8 production through the Smad3 signaling pathway in PBECs and alleviated lung inflammation/injury in CS-exposed mice. The anti-inflammatory effect of TGF-ß2 on CS-induced lung inflammation in humans deserves further clinical study.