Retrospective analysis of mortality among children under 5 years of age in Huangshi over the period 2002-2022, China.

BACKGROUND: The United Nations' Millennium Development Goals and Sustainable Development Goals both underscore the critical need to reduce the under-five mortality rate globally. China has made remarkable progress in decreasing the mortality rate of children under five. This study aims to examine the trends in child mortality rates from 2002 to 2022 and the causes of deaths among neonates, infants, and children under 5 years of age from 2013 to 2022 in Huangshi. METHODS: The data resource was supported and provided by the Huangshi Health Commission, Huangshi Maternal and Child Health Hospital, and the Huangshi Statistics Bureau. Figures were drawn using Origin 2021. RESULTS: The mortality rate among children under 5 years old significantly decreased, from 21.38 per 1,000 live births in 2002 to 3.53 per 1,000 live births in 2022. The infant mortality rate also saw a significant decline, to 15.06 per 1,000 live births. Among the 1,929 recorded child deaths from 2013 to 2022, the top three causes were: F2 (Disorders related to short gestation and low birth weight), accounting for 17.26% (333 deaths); I1 (Accidental drowning and submersion), for 14.83% (286 deaths); and I3 (Other accidental threats to breathing), for 12.29% (237 deaths). Of the 1,929 deaths, 1,117 were male children, representing 57.91%. The gender disparity in the Under-5 Mortality Rate (U5MR) was calculated to be 1.38 (boys to girls). The leading causes of death under the age of five shifted from F2 (Disorders related to short gestation and low birth weight) to I1 (Accidental drowning and submersion) as children aged, highlighting the need for policymakers and parents to intensify care and vigilance for children. CONCLUSIONS: Huangshi has achieved significant progress in lowering child mortality rates over the past two decades. The study calls for policymakers to enact more effective measures to further reduce the mortality rate among children under 5 years of age in Huangshi. Furthermore, it advises parents to dedicate more time and effort to supervising and nurturing their children, promoting a safer and healthier development.

The Metabolism of Coenzyme A and Its Derivatives Plays a Crucial Role in Diseases.

Coenzyme A (CoA) functions as a crucial carrier of acyl groups within cells, playing a fundamental role in regulating acyl transfer reactions and participating in cellular metabolic processes. As the principal substrate and cofactor engaged in diverse metabolic reactions, CoA and its derivatives exert central influence over various physiological processes, primarily modulating lipid and ketone metabolism, as well as protein modification. This paper presents a comprehensive review of the molecular mechanisms by which CoA influences the onset and progression of cancer, cardiovascular disease (CVD), neurodegenerative disorders, and other illnesses. The main focal points include the following. (1) In cancer, enzymes such as acetyl-CoA synthetase 2, ATP citrate lyase, and acetyl-CoA carboxylase regulate lipid synthesis and energy metabolism by modulating acetyl-CoA levels. (2) In CVD, the effects of enzymes such as stearoyl-CoA desaturase-1, 3-hydroxy-3-methylglutaryl-CoA (HMGC) synthase 2, and HMGC reductase on the formation and advancement of these diseases are elucidated by their regulation of CoA metabolism across multiple organs. (3) In neurodegenerative disorders, the significance of CoA in maintaining cholesterol homeostasis in the brain and its implications on the development of such disorders are thoroughly discussed. The metabolic processes involving CoA and its derivatives span all physiological aspects within cells, playing a critical role in the onset and progression of various diseases. Elucidating the role of CoA in these conditions yields important insights that can serve as valuable references and guidance for disease diagnosis, treatment, and drug development.

COVID-19 pandemic amplified mortality rates among adolescents with bipolar disorder through family-related factors.

BACKGROUND: Recently, a growing number of adolescents have been afflicted with mental disorders, with annual morbidity rates on the rise. This trend has been exacerbated by the global coronavirus disease 2019 (COVID-19) pandemic, leading to a surge in suicide and self-harm rates among this demographic. AIM: To investigate the impact of the COVID-19 pandemic on adolescent bipolar disorder (BD), along with the underlying factors contributing to heightened rates of suicide and self-harm among adolescents. METHODS: A comprehensive statistical analysis was conducted utilizing clinical interviews and self-reports obtained from patients or their guardians. Diagnostic criteria for BDs were based on the Diagnostic and statistical manual of mental disorders, international classification of diseases-11, and the National institute of mental health research domain criteria. Statistical analyses were performed using SPSS 26.0 software, with significance set at P < 0.05. RESULTS: A cohort of 171 adolescents diagnosed with BD between January 1, 2018, and December 31, 2022, was included in the analysis. The gender distribution was 2.8:1 (female to male), with ages ranging from 11 to 18 years old. Major factors contributing to adolescent BDs included familial influences, academic stress, genetic predisposition and exposure to school-related violence. Notably, a significant increase in suicide attempts and self-harm incidents was observed among adolescents with BD during the COVID-19 pandemic. Statistical analysis indicated that the pandemic exacerbated familial discord and heightened academic stress, thereby amplifying the prevalence of suicidal behavior and self-harm among adolescents. CONCLUSION: The COVID-19 pandemic has exacerbated familial tensions and intensified the incidence of suicide and self-harm among adolescents diagnosed with BD. This study underscores the urgent need for societal, familial and educational support systems to prioritize the well-being of adolescents and offers valuable insights and guidelines for the prevention, diagnosis and treatment of adolescent BDs.

Functional Insight into hTRIR.

The uncharacterized C19orf43 was discovered to be associated with hTR maturation. Our previous work indicated that C19orf43 cleaves distinct RNA types but not DNA. We then named it hTR-interacting RNase (hTRIR) (Uniprot: Q9BQ61). hTRIR works in a broad range of temperatures and pH without any divalent cations needed. hTRIR cleaves RNA at all four nucleotide sites but preferentially at purines. In addition, hTRIR digested both ends of methylated small RNA, which suggested that it was a putative ribonuclease. Later, we designed more nucleotides that methylated small RNA to determine whether it was an exo- and/or endoribonuclease. Unlike RNase A, hTRIR could digest both ends of methylated RNA oligos 5R5, which suggested it was potentially an endoribonuclease.

Descriptive analysis of depression among adolescents in Huangshi, China.

BACKGROUND: More adolescents suffered from depressive disorder, and what was worse, the morbidity increased annually. The situation was getting worse during COVID-19 pandemic. The prevalence of depression among adolescents in China has increased a lot due to social and economic development, family-associated reasons, academic stress, interpersonal relationships, and so on. OBJECTIVE: This study aimed to determine the prevalence, gender differences, risk factors, and abnormal illness behaviors of depression among adolescents in Huangshi, China. METHODS: A descriptive analysis was conducted based on the data from clinical interviews and self-reports by the patients. Depression was assessed and diagnosed using the DSM-5 Diagnostic and Statistical Manual of Mental Disorders. RESULTS: Depression was most frequently seen in 674 patients with mental illnesses (282, 41.84%). The male-to-female ratio was 1:2.44, and their age ranged from 9 to 18. The majority of patients are in high school (261/282, 92.55%), and the highest morbidity occurred at 16 years. More cases were diagnosed in urban than in rural areas. Genetic factors, school violence, academic stress, sleep disorders, and family-related factors were essential factors leading to depression among adolescents. Most patients had sleep disorders (84.75%). In family-related factors, left-behind children and unrecognized/misunderstood by their families were prominently diagnosed with depression. A large portion of individuals with depression felt apathetic, solitary, and sluggish and were unable to study, work, and live normally (212/282, 75.18%); they even committed suicide or attempted suicide (228/282, 80.85%) and inflicted self-harm (146/282, 51.77%). CONCLUSIONS: An increasing trend of depression has been observed since 2018, especially in 2021. This depression has led to suicide or suicidal attempts and self-harm, reflecting the severity of mental health among adolescents in Huangshi. Therefore, this study aimed to draw the attention of society, families, and schools to the importance of mental health among adolescents, providing guidance and references for the prevention, diagnosis, and treatment of young depressive disorders in China.

Descriptive and associated risk factors analysis of mental disorders among adolescents in Huangshi, China.

Descriptive analysis of adolescent mental disorders in Huangshi was performed to explore the gender differences, influencing factors, and abnormal illness behaviors. A total of 674 patients in Huangshi Mental Health Center from 2017 to 2022 were collected. A rising trend of mental disorders has been observed since 2018, especially during the COVID-19 pandemic. More young cases led to suicidal attempts and self-harm, which reflects the severity of mental health in adolescents. This study aims to draw the attention of government, society, families, and schools to care about adolescents, which also provides guidance and references for clinical treatment of mental disorders.

Exploration and validation of Taraxacum mongolicum anti-cancer effect.

Taraxacum mongolicum gained a lot of concern and was applied in 93 formulas in China due to its fame as a traditional Chinese medicine. The earliest recorded application of Taraxacum mongolicum was traced back to the Han dynasty. Generations of doctors boosted the usage and enriched the pharmacological mechanism. Clinical application of the Taraxacum mongolicum is flourishing as it treats multiple diseases. This study aims to explore the anti-cancer effect, retrieve the active ingredients and screen the key targets of Taraxacum mongolicum in cancer therapy. We collected and evaluated 10 key active compounds to investigate the anti-cancer effect via 69 significant targets and a variety of biological processes and pathways. Gene Ontology (GO) enrichment analysis uncovered targets associated with protein phosphorylation, cell proliferation and apoptotic processes via regulation of kinases, ATP and enzyme binding activities. Half of the top 20 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were directly involved in cancer. Based on standard selection criteria, seven hub targets were obtained. These targets functioned through distinct patterns and pathways in realizing the anti-cancer effect. Molecular docking was conducted to validate the potential combination between compounds and hub targets to explore the pharmacological mechanism of key compounds in Taraxacum mongolicum against cancer. In summary, our findings indicate that the famous and widely used Chinese herb, Taraxacum mongolicum, shows good anti-cancer effect through its active compounds, targeted genes, and multiple involved biological processes. The results may provide a theoretical basis for subsequent experimental validation and drug development of Taraxacum mongolicum extract against cancer.

Functional study of SCCD pathogenic gene UBIAD1 (Review).

Schnyder's crystalline corneal dystrophy (SCCD) is a rare autosomal dominant genetic disorder that is characterized by progressive corneal opacity, owing to aberrant accumulation of cholesterol and phospholipids in the cornea. A number of SCCD affected families have been reported in the world since 1924, when it was first described. In 2007, the molecular basis of SCCD was demonstrated to be associated with a tumor suppressor, UbiA prenyltransferase domain­containing 1 (UBIAD1), which was isolated from the bladder mucosa and demonstrated to be involved in vitamin K2 and CoQ10 biosynthesis. This sterol triggers the binding of UBIAD1 to 3­hydroxy­3­methyl­glutaryl coenzyme A reductase (HMGCR) at endoplasmic reticulum (ER) membranes, which is regulated by an intracellular geranylgeranyl diphosphate (GGpp) molecule. The inability of SCCD­associated UBIAD1 to bind GGpp results in the consistent binding of UBIAD1 to HMGCR at ER membranes. This binding leads to HMGCRs being redundant. Therefore, they cannot be degraded through ER­associated degradation to synthesize abundant cholesterol in tissue cells. Excess corneal cholesterol accumulation thus leads to SCCD disease. After decades, the efforts of numerous ophthalmologists and scientists have helped clarify the molecular basis and pathogenesis of SCCD, which has guided the effective diagnosis and treatment of this genetic disorder. However, more studies need to be conducted to understand the pathogenesis of SCCD disease from a genetic basis by studying the defective gene, UBIAD1. Results would guide effective diagnosis and treatment of the inherited eye disease.

Antimicrobial peptide CAMA-syn expressed in pulmonary epithelium by recombination adenovirus inhibited the growth of intracellular bacteria.

BACKGROUND: Intracellular bacteria, especially Mycobacterium tuberculosis, are important pathogenic microorganisms that endanger human health. Purified and synthesized cecropin A-magainin 2 (CAMA-syn) can exhibit a higher antibacterial activity and lower cytotoxicity. To enhance such antimicrobial potential, it would be desirable to deliver CAMA-syn expressed in lung epithelial cells by an adenovirus vector using gene therapy. METHODS: A549 cells in vitro and lung epithelial cells in vivo were used to express CAMA-syn by transducing recombinant adenovirus Ad-SPC-CAMA/GFP, and the expression of CAMA-syn was determined by a reverse transcriptase-polymerase reaction (RT-PCR) and immunofluorescence. The antimicrobial activity in cells was investigated by colony-forming rate and growth curve. Forty Kunming mice of a Bacillus Calmette-Guerin (BCG) infection animal model were randomly divided into three groups: adenoviruses delivery of Ad-SPC-CAMA/GFP, Ad-CMV-CAMA/GFP and empty-virus Ad-CMV-GFP. The expression of CAMA-syn in mice was confirmed by RT-PCR and immunofluorescence. After tracheal injection of adenoviral vector for 3 days, lungs from the mouse model were extracted and homogenized for detection of colony-forming efficiency. RESULTS: CAMA-syn expressed in lung epithelial cells A549 conferred antimicrobial activity against a series of bacteria, including Salmonella abortusovis and BCG. The results obtained in vivo showed that the colony-forming rate of Ad-SPC-CAMA/GFP (74.54%) and Ad-CMV-CAMA/GFP (62.31%) transduced into mice was significantly lower than that of the control group. CONCLUSIONS: Lung epithelial-specific expression of antimicrobial peptide CAMA-syn mediated by adenovirus suppressed the growth of intracellular bacteria, providing a promising approach for the control of refractory intracellular infection.

Identification of an RNase that preferentially cleaves A/G nucleotides.

Ribonucleases play an important role in the RNA metabolism which is critical for the localization, stability and function of mature RNA transcripts. More and more ribonucleases were discovered in recent years with the progress of technology. In the present study, we found that the uncharacterized C19orf43, a novel interacting protein of human telomerase RNA (hTR), digested T7 transcribed RNA, total cellular RNA and RNA oligos but not DNA. Thus we named this new RNase as hTRIR (human telomerase RNA interacting RNase). Genetic analysis showed that hTRIR is conserved among eukaryotic species and widely expressed in different cell lines. The RNase activity of hTRIR works in a broad temperature and pH range while divalent cations are not required. The conserved C-terminus of C19orf43 is necessary for its activity. Finally, we found that hTRIR cleaves all four unpaired RNA nucleotides from 5' end or 3' end with higher efficiency for purine bases, which suggested that hTRIR is an exoribonuclease. Taken together, our study showed the first evidence of the novel function of hTRIR in vitro, which provides clue to study the regulatory mechanism of hTR homeostasis in vivo.