Effects of water fluoridation on early embryonic development of zebrafish.

Fluoride has strong electronegativity and exposes diversely in nature. Water fluoridation is the most pervasive form of occurrence, representing a significant threat to human health. In this study, we investigate the morphometric and physiological alterations triggered by fluoride stimulation during the embryogenesis of zebrafish and reveal its putative effects of stage- and/or dose-dependent. Fluoride exhibits potent biological activity and can be extensively absorbed by the yolk sac, exerting significant effects on the development of multiple organs. This is primarily manifested as restricted nutrient utilization and elevated levels of lipid peroxidation, further leading to the accumulation of superoxide in the yolk sac, liver, and intestines. Moreover, pericardial edema exerts pressure on the brain and eye development, resulting in spinal curvature and reduced body length. Besides, acute fluoride exposure with varying concentrations has led to diverse teratogenic outcomes. A low dose of water fluoridation tends to induce abnormal development of the embryonic yolk sac, while vascular malformation is widely observed in all fluoride-treated groups. The effect of fluoride exposure on blood circulation is universally present, even in zebrafish larvae that do not exhibit obvious deformities. Their swimming behavior is also affected by water fluoridation, resulting in reduced activity and delayed reactions. In conclusion, this study provides valuable insights into the monitoring of environmental quality related to water fluoridation and disease prevention.

Effects of bepridil on early cardiac development of zebrafish.

Bepridil is a commonly used medication for arrhythmia and heart failure. It primarily exerts hemodynamic effects by inhibiting Na+/K+ movement and regulating the Na+/Ca2+ exchange. In comparison to other Ca2+ inhibitors, bepridil has a long half-life and a complex pharmacology. Additionally, it is widely used in antiviral research and the treatment of various diseases. However, the toxicity of this compound and its other possible effects on embryonic development are unknown. In this study, we investigated the toxicity of bepridil on rat myocardial H9c2 cells. After treatment with bepridil, the cells became overloaded with Ca2+ and entered a state of cytoplasmic vacuolization and nuclear abnormality. Bepridil treatment resulted in several morphological abnormalities in zebrafish embryo models, including pericardium enlargement, yolk sac swelling, and growth stunting. The hemodynamic effects on fetal development resulted in abnormal cardiovascular circulation and myocardial weakness. After inhibiting the Ca2+ transmembrane, the liver of zebrafish larvae also displayed an ectopic and deficient spatial location. Additionally, the results of the RNA-seq analysis revealed the detailed gene expression profiles and metabolic responses to bepridil treatment in zebrafish embryonic development. Taken together, our study provides an important evaluation of antiarrhythmic agents for clinical use in prenatal heart patients.

Dynamics of parainfluenza virus among hospitalized children with acute respiratory tract infection under two-child policy and COVID-19 pandemic in Hubei Province, China, 2014-2022.

To analyze changes in the detection of parainfluenza virus (PIV) in children hospitalized with acute respiratory tract infection (ARTI) during 2014-2022 in Hubei Province, and explore the impact of the universal two-child policy and the public health measures against COVID-19 epidemic on the prevalence of PIV in China. The study was conducted at the Maternal and Child Health Hospital of Hubei Province. Children aged <18 years with ARTI admitted from January 2014 to June 2022 were enrolled. The infection of PIV was confirmed by the direct immunofluorescence method in nasopharyngeal specimens. Adjusted logistic regression models were used to analyze the influence of the universal two-child policy implementation and public health measurements against COVID-19 on PIV detection. Totally 75 128 inpatients meeting the criteria were enrolled in this study from January 2014 to June 2022 with an overall PIV positive rate of 5.5%. The epidemic seasons of PIV prevalence lagged substantially in 2020. A statistically significant higher positive rate of PIV was observed in 2017-2019 compared to that in 2014-2015 (6.12% vs 2.89%, risk ratio = 2.12, p < 0.001) after the implementation of the universal two-child policy in 2016. A steep decline occurred in PIV positive rate during the COVID-19 epidemic in 2020 (0.92% vs 6.92%, p < 0.001) and it rebounded during the regular epidemic prevention and control period in 2021-2022 (6.35%, p = 0.104). In Hubei Province, the implementation of the universal two-child policy might have led to an increase of PIV prevalence, and public health measures during the COVID-19 epidemic might have influenced the fluctuation in PIV detection since 2020.

Epidemiological change of influenza virus in hospitalized children with acute respiratory tract infection during 2014-2022 in Hubei Province, China.

PURPOSE: Influenza virus (IFV) causes acute respiratory tract infection (ARTI) and leads to high morbidity and mortality annually. This study explored the epidemiological change of IFV after the implementation of the universal two-child policy and evaluated the impact of coronavirus disease 2019 (COVID-19) pandemic on the detection of IFV. METHODS: Hospitalized children under 18 years with ARTI were recruited from Hubei Maternal and Child Healthcare Hospital of Hubei Province from January 2014 to June 2022. The positive rates of IFV were compared among different periods by the implementation of the universal two-child policy and public health measures against COVID-19 pandemic. RESULTS: Among 75,128 hospitalized children with ARTI, the positive rate of IFV was 1.98% (1486/75128, 95% CI 1.88-2.01). Children aged 6-17 years had the highest positive rate of IFV (166/5504, 3.02%, 95% CI 2.58-3.50). The positive rate of IFV dropped to the lowest in 2015, then increased constantly and peaked in 2019. After the universal two-child policy implementation, the positive rate of IFV among all the hospitalized children increased from 0.40% during 2014-2015 to 2.70% during 2017-2019 (RR 6.72, 95% CI 4.94-9.13, P < 0.001), particularly children under one year shown a violent increasing trend from 0.20 to 2.01% (RR 10.26, 95% CI 5.47-19.23, P < 0.001). During the initial outbreak of COVID-19, the positive rate of IFV decreased sharply compared to that before COVID-19 (0.35% vs. 3.37%, RR 0.10, 95% CI 0.04-0.28, P < 0.001), and then rebounded to 0.91%, lower than the level before COVID-19 (RR 0.26, 95% CI 0.20-0.36, P < 0.001). CONCLUSION: IFV epidemiological pattern has changed after the implementation of the universal two-child policy. More attention should be emphasized to comprehend the health benefits generated by COVID-19 restrictions on IFV transmission in future.

Kinesin-14 KIFC1 modulates spindle assembly and chromosome segregation in mouse spermatocytes.

Kinesin-14 KIFC1 regulates spindle assembly and centrosome clustering in diverse organisms during cell division. KIFC1 proteins are essential for spindle assembly and chromosome alignment in mitosis. However, the roles and mechanisms of KIFC1 proteins in male spermatocytes remain largely unknown. In this study, we reveal that KIFC1 proteins mainly accumulate at the centrosomes and central spindle in mouse spermatocytes both in vitro and in vivo. We utilize two KIFC1 specific inhibitors, AZ82 and CW069, for the inhibition of KIFC1 in mouse spermatogenic cells and cultured GC-2 spd(ts) cells. We find that KIFC1 inhibition results in the increase of spermatocytes with micronuclei, the disorganization of the meiotic spindles, and the formation of multiple centrosomes. Furthermore, we demonstrate that KIFC1 inhibition leads to spindle defects, chromosome misalignment and the formation of aneuploidy in cultured GC-2 spd(ts) cells. In this study, we reveal that KIFC1 proteins are critical for centrosome maintenance and chromosome stability in mouse spermatocytes.

Chiral Luminescent Sensor Eu-BTB@d-Carnitine Applied in the Highly Effective Ratiometric Sensing of Curing Drugs and Biomarkers for Diabetes and Hypertension.

Chiral drugs are of great significance in drug development and life science because one pair of enantiomers has a different combination mode with target biological active sites, leading to a vast difference in physical activity. Metal-organic framework (MOF)-based chiral hybrid materials with specific chiral sites have excellent applications in the highly effective sensing of drug enantiomers. Sitagliptin and clonidine are effective curing drugs for controlling diabetes and hypertension, while insulin and norepinephrine are the biomarkers of these two diseases. Excessive use of sitagliptin and clonidine can cause side effects such as stomach pain, nausea, and headaches. Herein, through post-synthetic strategy, MOF-based chiral hybrid material Eu-BTB@d-carnitine (H3BTB = 1,3,5-benzenetrisbenzoic acid) was synthesized. Eu-BTB@d-carnitine has dual emission peaks at 417 and 616 nm when excited at 330 nm. Eu-BTB@d-carnitine can be applied in luminescent recognition toward sitagliptin and clonidine with high sensitivity and low detection limit (for sitagliptin detection, Ksv is 7.43 × 106 [M-1]; for clonidine detection, Ksv is 9.09 × 106 [M-1]; limit of detection (LOD) for sitagliptin is 10.21 nM, and LOD of clonidine is 8.34 nM). In addition, Eu-BTB@d-carnitine can further realize highly sensitive detection of insulin in human fluids with a high Ksv (2.08 × 106 [M-1]) and a low LOD (15.48 nM). On the other hand, norepinephrine also can be successfully discriminated by the hybrid luminescent platform of Eu-BTB@d-carnitine and clonidine with a high Ksv value of 4.79 × 106 [M-1] and a low LOD of 8.37 nM. As a result, the chiral hybrid material Eu-BTB@d-carnitine can be successfully applied in the highly effective ratiometric sensing of curing drugs and biomarkers for diabetes and hypertension.

Driving force to detect Alzheimer's disease biomarkers: application of a thioflavine T@Er-MOF ratiometric fluorescent sensor for smart detection of presenilin 1, amyloid ß-protein and acetylcholine.

Currently, the highly sensitive detection of Alzheimer's Disease (AD) biomarkers, namely presenilin 1, amyloid ß-protein (Aß), and acetylcholine (ACh), is vital to helping us prevent and diagnose AD. In this work, a novel metal-organic framework [Er(L)(DMF)1.27]n (Er-MOF) (H3L = terphenyl-3,4'',5-tricarboxylic acid) has been synthesized by solvothermal and ultrasonic methods. Further, through the post-synthesis assembly strategy, the fluorescent dye thioflavine T (ThT) has been introduced into Er-MOF to construct a dual-emission ThT@Er-MOF ratiometric fluorescent sensor. This is the first time that ThT@Er-MOF has been successfully applied in the highly sensitive detection of three main Alzheimer's disease biomarkers in the cerebrospinal fluid through three different low cost and facile detection strategies. Firstly, with the spilted DNA strategy, this is the first time that ThT@Er-MOF can be applied in the label-free detection of SSODN (part of the presenilin 1 gene). Secondly, for the detection of Aß, because ThT can be specifically combined with Aß and has an excellent characteristic fluorescence band, the dual-emission ThT@Er-MOF sensor can be selectively applied to detect Aß over the analog protein, which shows far more sensitivity than other Aß sensors. Thirdly, through the acetylcholine esterase (AchE) enzymatic cleavage and release strategy, ThT@Er-MOF enhances the detection of acetylcholine (ACh) with a low limit of detection (LOD) value (0.03226 nM). It should be noticed that the three different detection methods are low cost and facile. This study also provides the first example of utilizing laser scanning confocal microscopy (LSCM) to investigate the fluorescence resonance energy transfer (FRET) detection mechanism by ThT@Er-MOF in more detail. The location of FRET occurrence and FRET efficiency can also be investigated by LSCM, which can be helpful to understand the FRET detection process by these unique MOF-based hybrid materials.

Solvothermal and Ultrasonic Preparation of Two Unique Cluster-Based Lu and Y Coordination Materials: Metal-Organic Framework-Based Ratiometric Fluorescent Biosensor for an Ornidazole and Ronidazole and Sensing Platform for a Biomarker of Amoeba Liver Abscess.

Through powerful solvothermal and facile ultrasonic synthetic strategies, two unique cluster-based lanthanide Lu and Y nanoporous metal organic frameworks (MOFs) have been successfully prepared, namely, {[Lu2(L)2]·2DMF·H2O}n (Lu-MOF) and [Y(L)(DMF)0.75]n (Y-MOF) (H3L = terphenyl-3,4'',5-tricarboxylic acid). In addition, both the morphologies and nanosizes of Lu-MOF and Y-MOF materials also have been deliberately tuned by adjustable ultrasonic conditions including irradiation time (40, 60, and 80 min) and power (70 w, 100 w). Currently, it is noted that the abuse of antibiotics such as ornidazole and ronidazole leads to great damage to human health, and therefore the development of highly effective and facile detection methods for ornidazole and ronidazole is quite important. Herein, to improve the fluorescent sensing sensitivity of antibiotics, Eu3+ and Tb3+ have been introduced into Lu-MOF (under a solvothermal preparation method) to fabricate a dual-emission hybrid material Eu3+/Tb3+@Lu-MOF through a postsynthesis strategy, which can be successfully applied as a self-calibrated ratiometric fluorescent sensor for ornidazole and ronidazole with high selectivity and sensitivity (the Ksv value for ornidazole is 1.0854 × 106 [M-1], and the Ksv value for ronidazole is 1.0595 × 107 [M-1]) and low detection limit values (2.85 nM for ornidazole and 26.7 nM for ronidazole). On the other hand, amoeba liver abscess (ALA) will easily lead to irregular fever, night sweats, and other tortured symptoms; C-reactive protein autoantibody (CRP Ab) is the important biomarker for the detection of ALA. Given this, Y-MOF (under the solvothermal preparation method) also has been successfully designed to combine FAM-labeled NH-ssDNA to construct the scarcely reported excellent hybrid FAM-labeled NH-ssDNA/Y-MOF sensing platform for the highly effective discrimination of CRP Ab with excellent sensitivity and selectivity in real samples such as human serum solution.

Water-soluble host-guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres.

A sugar-functionalized water-soluble tribenzotriquinacene derivative bearing six glucose residues, TBTQ-(OG) 6 , was synthesized and its interaction with C60 and C70-fullerene in co-organic solvents and aqueous solution was investigated by fluorescence spectroscopy and ultraviolet-visible spectroscopy. The association stoichiometry of the complexes TBTQ-(OG) 6 with C60 and TBTQ-(OG) 6 with C70 was found to be 1:1 with binding constants of K a = (1.50 ± 0.10) × 105 M-1 and K a = (2.20 ± 0.16) × 105 M-1, respectively. The binding affinity between TBTQ-(OG) 6 and C60 was further verified by Raman spectroscopy. The geometry of the complex of TBTQ-(OG) 6 with C60 deduced from DFT calculations indicates that the driving force of the complexation is mainly due to the hydrophobic effect and to host-guest π-π interactions. Hydrophobic surface simulations showed that TBTQ-(OG) 6 and C60 forms an amphiphilic supramolecular host-guest complex, which further assembles to microspheres with diameters of 0.3-3.5 µm, as determined by scanning electron microscopy.

Hydrothermal Preparation of Five Rare-Earth (Re = Dy, Gd, Ho, Pr, and Sm) Luminescent Cluster-Based Coordination Materials: The First MOFs-based Ratiometric Fluorescent Sensor for Lysine and Bifunctional Sensing Platform for Insulin and Al3.

Through the powerful hydrothermal method, five rare-earth (Re = Dy, Gd, Ho, Pr, and Sm) three-dimensional (3D) cluster-based metal-organic frameworks (MOFs) have been synthesized, namely, [Dy(L)(H2O)(DMF)] n (1), {[Gd(L)(H2O)(DMF)]·DMF} n (2), {[Ho(L)(H2O)(DMF)]·0.5DMF} n (3), {[Pr(L)(H2O)(DMF)]·0.5DMF} n (4), and {[Sm(L)(H2O)1.55(DMF)0.45]·DMF} n (5; H3L = terphenyl-3,4″,5-tricarboxylic acid), which have been determined by single crystal X-ray analyses and PXRD characterization. Structural analyses reveal that, in 1-5, these L3- ligands are linked by five different rare-earth centers, forming the iso-structural nanoporous frameworks. PXRD patterns of bulky samples 1-5 also are consistent with theoretical PXRD patterns confirming their purity. Solid state photoluminesce of free H3L and 1-5 at room temperature also has been investigated indicating strong ligand-based emissions. Besides these, fluorescent dye Rhodamine B (RhB) can be introduced into MOF1 forming the composite material RhB@MOF1 with a high quantum yield of 35%. It is noted that, through deliberately tuning the morphologies of nanoparticle MOF1 under different ultrasonic conditions, RhB@MOF1 can be utilized as the first ratiometric fluorescent sensor to effectively discriminate l- and d-lysine from other amino acid molecules with high Ksv values and low LOD values. On the other hand, 2 was for the first time to be utilized as an excellent bifunctional MOFs-based sensing platform to detect insulin and Al3+ with a low detection limit in the human serum solution.

Evidence for parallel evolution of a gene involved in the regulation of spermatogenesis.

PHD finger protein 7 (Phf7) is a male germline specific gene in Drosophila melanogaster that can trigger the male germline sexual fate and regulate spermatogenesis, and its human homologue can rescue fecundity defects in male flies lacking this gene. These findings prompted us to investigate conservation of reproductive strategies through studying the evolutionary origin of this gene. We find that Phf7 is present only in select species including mammals and some insects, whereas the closely related G2/M-phase specific E3 ubiquitin protein ligase (G2e3) is in the genome of most metazoans. Interestingly, phylogenetic analyses showed that vertebrate and insect Phf7 genes did not evolve from a common Phf7 ancestor but rather through independent duplication events from an ancestral G2e3 This is an example of parallel evolution in which a male germline factor evolved at least twice from a pre-existing template to develop new regulatory mechanisms of spermatogenesis.

Preterm birth and detection of common respiratory pathogens among pediatric pneumonia.

Pneumonia complicated by preterm birth is related to adverse clinical sequelae from the neonatal period to childhood. Children with pneumonia during 2009-2021 were enrolled at the Children's Hospital of Chongqing Medical University. Altogether 20 respiratory pathogens were detected and compared. Among 8,206 children, 779 were in the preterm group with 246 of early-preterm and 533 of late preterm. The positive rates for all viral pathogens were comparable between the preterm group and the full-term group. For bacterial pathogens, higher positive rates for Escherichia coli and Klebsiella pneumoniae were observed in the preterm group. Severe pneumonia developed in 16.52% of all, which was higher in the preterm group than in the full-term group. A significantly higher rate of severe pneumonia was observed in the early-preterm group compared to the late-preterm group. Preterm birth has an impact on the detection of bacterial pathogens in children and is a risk factor for severe pneumonia.

Nono deficiency impedes the proliferation and adhesion of H9c2 cardiomyocytes through Pi3k/Akt signaling pathway.

Congenital heart disease (CHD) is the most common type of birth defect and the main noninfectious cause of death during the neonatal stage. The non-POU domain containing, octamer-binding gene, NONO, performs a variety of roles involved in DNA repair, RNA synthesis, transcriptional and post-transcriptional regulation. Currently, hemizygous loss-of-function mutation of NONO have been described as the genetic origin of CHD. However, essential effects of NONO during cardiac development have not been fully elucidated. In this study, we aim to understand role of Nono in cardiomyocytes during development by utilizing the CRISPR/Cas9 gene editing system to deplete Nono in the rat cardiomyocytes H9c2. Functional comparison of H9c2 control and knockout cells showed that Nono deficiency suppressed cell proliferation and adhesion. Furthermore, Nono depletion significantly affected the mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis, resulting in H9c2 overall metabolic deficits. Mechanistically we demonstrated that the Nono knockout impeded the cardiomyocyte function by attenuating phosphatidyl inositol 3 kinase-serine/threonine kinase (Pi3k/Akt) signaling via the assay for transposase-accessible chromatin using sequencing in combination with RNA sequencing. From these results we propose a novel molecular mechanism of Nono to influence cardiomyocytes differentiation and proliferation during the development of embryonic heart. We conclude that NONO may represent an emerging possible biomarkers and targets for the diagnosis and treatment of human cardiac development defects.

Near-infrared magnetic core-shell nanoparticles based on lanthanide metal-organic frameworks as a ratiometric felodipine sensing platform.

Felodipine is an effective drug to treat hypertension, but its abuse can cause bardycardia. It is significant to develop highly sensitive detection platform for felodipine to enable the efficient treatment of hypertension diseases. In this work, to highly efficiently detect felodipine, multi-emission near-infrared (NIR) hierarchical magnetic core-shell lanthanide-MOF nanoparticles, namely Nd-MOF@Yb-MOF@SiO2@Fe3O4 (NIR-1), has been synthesized by layer-by-layer (LBL) method. LBL method can adjust the optical properties of NIR-1 and expose more active sites to improve sensitivity in detection process. NIR-1 has near-infrared luminescence emission, which can efficiently avoid the interference of autofluorescence in biological tissues. Photo-luminescent (PL) experiments also reveal that NIR-1 could be used as a near-infrared ratiometric luminescent sensor for felodipine detection with high selectivity and sensitivity, the low of detection limit (LOD) is 6.39 nM in felodipine detection, which is also performed using real biological samples. In addition, NIR-1 can be used as a ratiometric thermometer could also be applied in the temperature sensing from 293 K to 343 K. Finally, detection mechanisms for felodipine and temperature sensing performance based on near-infrared (NIR) emission were also investigated and discussed in detail.

Epidemiological Characteristics of Respiratory Syncytial Virus Infection Among Hospitalized Children With Acute Respiratory Tract Infections From 2014 to 2022 in a Hospital in Hubei Province, China: Longitudinal Surveillance Study.

BACKGROUND: Longitudinal studies characterizing the epidemic trend of respiratory syncytial virus (RSV) in Hubei Province are scarce. OBJECTIVE: We aimed to depict the dynamics of the RSV epidemic among hospitalized children with acute respiratory tract infections (ARTIs) during 2014 to 2022 in the Maternal and Child Health Hospital of Hubei Province and investigate the influence of the 2-child policy and the COVID-19 pandemic on RSV prevalence. METHODS: The medical records and testing results of hospitalized children with ARTI from January 2014 to June 2022 were extracted. Nasopharyngeal samples were tested with direct immunofluorescence assay. Detection rates of RSV were categorized according to the diagnosis of patients: (1) overall, (2) upper respiratory tract infection (URTI), and (3) lower respiratory tract infection (LRTI). Poisson regression models were used to investigate the association between RSV detection rate and age, gender, or diagnosis. The detection rates of RSV before and after the implementation of the universal 2-child policy were compared using a Poisson regression model. Multiple comparisons of RSV detection rates were conducted among 3 stages of the COVID-19 pandemic using chi-square tests. Seasonal autoregressive integrated moving average was performed to predict RSV behaviors from February 2020 to June 2020 under the assumption of a non-COVID-19 scenario. RESULTS: Among 75,128 hospitalized children with ARTI, 11.1% (8336/75,128) were RSV-positive. Children aged <1 year had higher detection rates than older children (4204/26,498, 15.9% vs 74/5504, 1.3%; P<.001), and children with LRTI had higher detection rates than children with URTI (7733/53,145, 14.6% vs 603/21,983, 2.7%; P<.001). Among all the children, a clear seasonal pattern of the RSV epidemic was observed before 2021. Most of the highest detection rates were concentrated between December and February. The yearly detection rate of RSV remained at a relatively low level (about 8%) from 2014 to 2017, then increased to 12% and above from 2018. The highest monthly detection rate was in December 2018 (539/1493, 36.1%), and the highest yearly rate was in 2021 (1372/9328, 14.7%). There was a moderate increase in the RSV detection rate after the 2-child policy was implemented (before: 860/10,446, 8.2% vs after: 4920/43,916, 11.2%; P<.001). The largest increase, by 5.83%, occurred in children aged <1 year. The RSV epidemic level decreased sharply in the short term after the COVID-19 outbreak (detection rate before: 1600/17,010, 9.4% vs after: 32/1135, 2.8%; P<.001). The largest decrease, by 12.0%, occurred in children aged <1 year, but a rebounding epidemic occurred after 2020 (680/5744, 11.8%; P<.001). CONCLUSIONS: Children have been experiencing increased prevalence of RSV since 2018 based on surveillance from a hospital in Hubei Province with a large sample size. The 2-child policy might have increased the RSV prevalence, and the COVID-19 epidemic had a temporary inhibitory effect on RSV transmission. Vaccines against RSV are urgently needed.

Kinesin-14 KIFC1 promotes acrosome formation and chromatin maturation during mouse spermiogenesis.

KIFC1, a member of kinesin-14 subfamily motors, is essential for meiotic cell division and acrosome formation during spermatogenesis. However, the functions of KIFC1 in the formation and maintenance of the acrosome in male germ cells remain to be elucidated. In this study, we report the structural deformities of acrosomes in the in vivo KIFC1 inhibition mouse models. The proacrosomal vesicles diffuse into the cytoplasm and form atypical acrosomal granules. This phenotype is consistent with globozoospermia patients and probably results from the failure of the Golgi-derived vesicle trafficking and actin filament organization. Moreover, the multinucleated and undifferentiated spermatogenic cells in the epidydimal lumen after KIFC1 inhibition reveal the specific roles of KIFC1 in regulating post-meiotic maturation. Overall, our results uncover KIFC1 as an essential regulator in the trafficking, fusion and maturation of acrosomal vesicles during spermiogenesis.

Disease Prevalence and Fatality, Life History Strategies, and Behavioral Control of the COVID Pandemic.

The COVID-19 pandemic caught the world by surprise and raised many questions. One of the questions is whether infectious diseases indeed drive fast life history (LH) as the extent research suggests. This paper challenges this assumption and raises a different perspective. We argue that infectious diseases enact either slower or faster LH strategies and the related disease control behavior depending on disease severity. We tested and supported the theorization based on a sample of 662 adult residents drawn from all 32 provinces and administrative regions of mainland China. The findings help to broaden LH perspectives and to better understand unusual social phenomena arising from the COVID-19 pandemic.

A method of large DNA fragment enrichment for nanopore sequencing in region 22q11.2.

Background: 22q11.2 deletion syndrome (22q11.2DS) is a disorder caused when a small part of chromosome 22 is missing. Diagnosis is currently established by the identification of a heterozygous deletion at chromosome 22q11.2 through chromosomal microarray analysis or other genomic analyses. However, more accurate identification of the breakpoint contributes to a clearer understanding of the 22q11.2 deletion syndrome. Methods: In this study, we present a feasible nanopore sequencing method of 22q11.2 deletion. This DNA enrichment method-region-specific amplification (RSA)-is able to analyze the 22q11.2 deletion by specific amplification of an approximately 1-Mb region where the breakpoint might exist. RSA introduces universal primers into the target region DNA by a Y-shaped adaptor ligation and a single primer extension. The enriched products, completed by amplification with universal primers, are then processed by standard ONT ligation sequencing protocols. Results: RSA is able to deliver adequate coverage (>98%) and comparable long reads (average length >1 Kb) throughout the 22q11.2 region. The long nanopore sequencing reads, derived from three umbilical cord blood samples, have facilitated the identification of the breakpoint of the 22q11.2 deletion, as well as by Sanger sequencing. Conclusion: The Oxford Nanopore MinION sequencer can use RSA to sequence the target region 22q11.2; this method could also be used for other hard-to-sequence parts of the genome.

Comprehensive analysis of an autophagy-related prognostic model for predicting survival based on TCGA and ICGC database in hepatocellular carcinoma patients.

Background: There is accumulating evidence that autophagic activity is crucial to the development of hepatocellular carcinoma (HCC). Thus, we sought to develop a predictive model based on autophagy-related genes (ARGs) to forecast the prognosis of HCC patients. Methods: Based on expression data from The Cancer Genome Atlas (TCGA) and ARGs from Human Autophagy Database (HADb), the differentially expressed ARGs were screened. The prognosis-related ARGs were identified using a univariate Cox regression analysis. Using multivariate Cox regression analysis, a prognostic model was developed. To assess the predictive value of the model, receiver operating characteristic (ROC) curve, Kaplan-Meier curve, and multivariable Cox regression analyses were conducted. A data cohort gathered independently from the International Cancer Genome Consortium (ICGC) database further verified the model's predictive accuracy. The immune landscape was generated using the TIMER and CIBERSORT algorithms. Finally, the correlation between the prognostic signature and gene mutation status was analyzed by employing "maftools" package. Results: We identified a novel prediction model based on the ARGs of PLD1 and SLC36A1 with significant prognostic values for HCC in both univariate and multivariate Cox regression analysis, and patients were classified into high- or low-risk groups based on their risk scores. High-risk patients had significantly shorter overall survival (OS) times than low-risk patients (P=5e-4). According to the ROC curve analysis, the risk score had a higher predictive value than the other clinical characteristics. Prognostic nomograms were also performed to visualize the relationship between individual predictors and survival rates in patients with HCC. Further, an external independent cohort of ICGC patients provided additional confirmation of the predictive efficacy of the model. We subsequently analyzed the differential immune densities of the two groups and discovered that various immune cells, including naïve B cells, resting memory cluster of differentiation (CD)4 T cells, regulatory T cells, M2 macrophages, and neutrophils, had considerably larger infiltrating densities in the high-risk group than the low-risk group. Conclusions: We established a robust autophagy-related risk model having a certain prediction accuracy for predicting the prognosis of HCC patients. Our findings will contribute to the definition of prognosis and establishment of personalized treatment interventions for HCC patients.

The phytochrome-interacting factor DcPIF3 of carrot plays a positive role in drought stress by increasing endogenous ABA level in Arabidopsis.

The phytochrome-interacting factor (PIF) subfamily of basic helix-loop-helix (bHLH) transcription factors plays a critical role in plant growth and development. However, there has been no detailed report on the PIFs in carrot. In this study, we present the identification and characterization of DcPIF gene family in carrot (Daucus carota L.). Phylogenetic analysis indicated that PIFs from carrot and other five plant species could be divided into four groups supported by similar gene structure and motif analysis. Expression profiles showed that all DcPIF genes were tissue-specific and could be induced by drought or abscisic acid (ABA) treatment except DcPIF7.1, among which DcPIF3 was the most responsive. The DcPIF3-overexpressed Arabidopsis plants exhibited more tolerance to drought stress, with higher antioxidant capacity and lower malondialdehyde content after drought treatment than wild type plants. Further stress tolerance assays revealed that DcPIF3 plays a positive role in drought stress by increasing endogenous ABA level and promoting the expression of ABA-related genes. Our results can enrich the understanding of DcPIF family genes and lay a foundation for further investigation of DcPIF3 function to defend against drought stress in carrot.