T-Type Ca2+ Channels Mediate a Critical Period of Plasticity in Adult-Born Granule Cells.

Adult-born granule cells (abGCs) exhibit a transient period of elevated synaptic plasticity that plays an important role in hippocampal function. Various mechanisms have been implicated in this critical period for enhanced plasticity, including minimal GABAergic inhibition and high intrinsic excitability conferred by T-type Ca2+ channels. Here we assess the contribution of synaptic inhibition and intrinsic excitability to long-term potentiation (LTP) in abGCs of adult male and female mice using perforated patch recordings. We show that the timing of critical period plasticity is unaffected by intact GABAergic inhibition such that 4-6-week-old abGCs exhibit LTP that is absent by 8 weeks. Blocking GABAA receptors, or partial blockade of GABA release from PV and nNos-expressing interneurons by a µ-opioid receptor agonist, strongly enhances LTP in 4-week-old GCs, suggesting that minimal inhibition does not underlie critical period plasticity. Instead, the closure of the critical period coincides with a reduction in the contribution of T-type Ca2+ channels to intrinsic excitability, and a selective T-type Ca2+ channel antagonist prevents LTP in 4-week-old but not mature GCs. Interestingly, whole-cell recordings that facilitate T-type Ca2+ channel activity in mature GCs unmasks LTP (with inhibition intact) that is also sensitive to a T-type Ca2+ channel antagonist, suggesting T-type channel activity in mature GCs is suppressed by native intracellular signaling. Together these results show that abGCs use T-type Ca2+ channels to overcome inhibition, providing new insight into how high intrinsic excitability provides young abGCs a competitive advantage for experience-dependent synaptic plasticity.

Sex reporting of cells used in cancer research: A systematic review.

Sex and gender disparities in biomedical research have been emphasized to improve scientific knowledge applied for the health of both men and women. Despite sex differences in cancer incidence, prognosis, and responses to therapeutic agents, mechanistic explanations at molecular levels are far from enough. Recent studies suggested that cell sex is an important biological variable due to differences in sex chromosome gene expression and differences in events associated with developmental biology. The objective of this study was to analyze the reporting of sex of cells used in cancer research using articles published in Cancer Cell, Molecular Cancer, Journal of Hematology & Oncology, Journal for ImmunoTherapy of Cancer, and Cancer Research in 2020, and to examine whether there exists any sex bias. We found that the percentage of cells with sex notation in the article was 36.5%. Primary cells exhibited higher sex notation compared to cell lines. A higher percentage of female cells were used in cell cultures with sex notation. Also, sex-common cells omitted sex description more often compared to sex-specific cells. None of the cells isolated from embryo and esophagus reported the cell sex in the article. Our results indicate cell sex report in cancer research is limited to a small proportion of cells used in the study. These results call for acknowledging the sex of cells to increase the applicability of biomedical research discoveries.

Sialylated IVIg promotes clinical improvements in a rabbit dry eye model by regulating inflammatory cytokines.

Dry eye disease (DED) is caused by a loss of homeostasis of the tear film, which results in visual disturbance, ocular surface inflammation and damage, and neurosensory abnormalities. Although it is prevalent in 5-50% of the global population, there are limited clinical options for its treatment. This study explored the potential use of human intravenous immunoglobulin (IVIg) and its enriched fractions of sialylation, sialylated IVIg (sIVIg), as a treatment for DED. Fifteen female New Zealand white rabbits were topically instilled with 0.2% benzalkonium chloride (BAC) twice daily for five consecutive days to induce experimental dry eye. Saline, 0.4% IVIg, or 0.04% sIVIg eye drops were instilled twice daily for 20 consecutive days. Clinical evaluations, such as non-invasive tear break-up time (NIBUT) and corneal fluorescein staining (CFS), were conducted. mRNA levels of mucin 4, mucin 16, TNF-α, IL-1ß, MMP9, IL-10, TGF-ß, and CD209 in rabbit conjunctival tissues were examined using reverse transcription polymerase chain reaction (RT-PCR) or quantitative RT-PCR (qRT-PCR). The relationships between CD209 family members in rabbits and various mammalian species were analyzed using a phylogenetic tree. IVIg or sIVIg treatment resulted in clinical improvements in the rabbit DED model. The inflammatory cytokines, TNF-α and IL-1ß, were increased and mucin 4 and mucin 16, cell surface-associated mucins, were decreased in BAC-induced dry eye. Following IVIg or sIVIg treatment, inflammatory cytokines decreased, whereas the anti-inflammatory cytokine, IL-10, increased substantially. Moreover, a 10-fold lower sIVIg treatment dose resulted in prolonged IL-10 production, representing a significantly improved DED compared to IVIg. Furthermore, the expression of rabbit CD209 mRNA in the rabbit conjunctiva and its close relationship with primate homologs suggest that it may interact with IVIg or sIVIg to promote IL-10 expression, as previously described in humans. At a lower dosage, sIVIg showed a more efficient improvement in DED, making it a promising new candidate medication for DED.

Dermatobacter hominis gen. nov., sp. nov., a new member of the family Iamiaceae, revealed the potential utilisation of skin-derived metabolites.

A non-motile, novel actinobacterial strain, Kera-3T, which is a gram-positive, aerobic, rod-shaped bacterium, was isolated from human keratinocytes on 1/10 diluted R2A agar. Whole-cell hydrolysis of amino acids revealed the presence of meso-DAP, alanine, and glutamic acid. The predominant menaquinone was MK-9 (H8), whereas the primary fatty acids were C16:0 and C18:1 ω9c. The major phospholipids included diphosphatidylglycerol and aminophospholipids, along with an unidentified phosphoglycolipid and an aminophosphoglycolipid. The G+C content of the genomic DNA was 73.2%, based on the complete genome sequence. Phylogenetic analyses of the 16S rRNA gene sequence and phylogenomic analysis of 91 core genes showed that strain Kera-3T formed a new lineage in the family Iamiaceae, with the closest neighbour Rhabdothermincola sediminis SYSU G02662T having 91.19% 16S rRNA gene sequence identity. A comparative genomic study of the predicted general metabolism and carbohydrate-active enzymes supported the phylogenetic and phylogenomic data. Based on the analysis of physiological, biochemical, and genomic characteristics, strain Kera-3T can be distinguished from known genera in the family Iamiaceae and represents a novel genus and species. Therefore, the name Dermatobacter hominis gen. nov., sp. nov. was proposed, with the type strain Kera-3T (= KACC 22415T = LMG 32493T).

The Adverse Effects and Nonmedical Use of Methylphenidate Before and After the Outbreak of COVID-19: Machine Learning Analysis.

BACKGROUND: Methylphenidate is an effective first-line treatment for attention-deficit/hyperactivity disorder (ADHD). However, many adverse effects of methylphenidate have been recorded from randomized clinical trials and patient-reported outcomes, but it is difficult to determine abuse from them. In the context of COVID-19, it is important to determine how drug use evaluation, as well as misuse of drugs, have been affected by the pandemic. As people share their reasons for using medication, patient sentiments, and the effects of medicine on social networking services (SNSs), the application of machine learning and SNS data can be a method to overcome the limitations. Proper machine learning models could be evaluated to validate the effects of the COVID-19 pandemic on drug use. OBJECTIVE: To analyze the effect of the COVID-19 pandemic on the use of methylphenidate, this study analyzed the adverse effects and nonmedical use of methylphenidate and evaluated the change in frequency of nonmedical use based on SNS data before and after the outbreak of COVID-19. Moreover, the performance of 4 machine learning models for classifying methylphenidate use based on SNS data was compared. METHODS: In this cross-sectional study, SNS data on methylphenidate from Twitter, Facebook, and Instagram from January 2019 to December 2020 were collected. The frequency of adverse effects, nonmedical use, and drug use before and after the COVID-19 pandemic were compared and analyzed. Interrupted time series analysis about the frequency and trends of nonmedical use of methylphenidate was conducted for 24 months from January 2019 to December 2020. Using the labeled training data set and features, the following 4 machine learning models were built using the data, and their performance was evaluated using F-1 scores: naïve Bayes classifier, random forest, support vector machine, and long short-term memory. RESULTS: This study collected 146,352 data points and detected that 4.3% (6340/146,352) were firsthand experience data. Psychiatric problems (521/1683, 31%) had the highest frequency among the adverse effects. The highest frequency of nonmedical use was for studies or work (741/2016, 36.8%). While the frequency of nonmedical use before and after the outbreak of COVID-19 has been similar (odds ratio [OR] 1.02 95% CI 0.91-1.15), its trend has changed significantly due to the pandemic (95% CI 2.36-22.20). Among the machine learning models, RF had the highest performance of 0.75. CONCLUSIONS: The trend of nonmedical use of methylphenidate has changed significantly due to the COVID-19 pandemic. Among the machine learning models using SNS data to analyze the adverse effects and nonmedical use of methylphenidate, the random forest model had the highest performance.

Preparation of Porous Hydroxyethyl Cellulose Materials to Utilize Lactic Acid with Vacuum-Assisted Process.

For the first time, we succeeded in manufacturing a 2-hydroxyethyl cellulose (HEC)-based composite membrane with improved thermal stability, for use as a battery separator, coating a HEC polymer solution to a polypropylene (PP) support and using a vacuum-assisted process. A HEC polymer solution was prepared by utilizing HEC and lactic acid (LA) as a plasticizer. A vacuum-assisted process was used to move ethanol, which a mobile phase to permeate a plasticized region in the HEC polymer side for pore formation. The pores formed with uniform nano sizes, and areas in which some large pores formed were observed. The thermal stability of the composites was measured using TGA. The thermal decomposition temperatures were measured at about 250 °C for the neat HEC, about 210 °C for the HEC/LA film, and about 335 °C for the HEC/LA/PP membrane before the process. After the vacuum-assisted process, the first and second thermal decomposition were observed at about 360 °C and 450 °C, respectively. The HEC/LA/PP membrane after the process showed greater thermal stability than before the process. This means that the adhesion between the HEC polymer and the PP support was created through the rearrangement of the HEC chain, as LA escaped after the process, and it was seen indirectly that the mechanical strength was enhanced. In particular, the surface of the membrane was observed by SEM to investigate whether the HEC penetrated into the PP to block its pores, and whether the HEC region collapsed. Furthermore, the interaction of the HEC chain with the additives and the rearrangement of the HEC was confirmed using FT-IR. As a result, we demonstrated that the mechanical strength and thermal stability of the manufactured HEC/LA/PP membrane were enhanced.

Next-Generation Digital Polymerase Chain Reaction: High-Dynamic-Range Single-Molecule DNA Counting via Ultrapartitioning.

Digital PCR (dPCR) was first conceived for single-molecule quantitation. However, current dPCR systems often require DNA templates to share partitions due to limited partitioning capacities. Here, we introduce UltraPCR, a next-generation dPCR system where DNA counting is performed in a single-molecule regimen through a 6-log dynamic range using a swift and parallelized workflow. Each UltraPCR reaction is divided into >30 million partitions without microfluidics to achieve single template occupancy. Combined with a unique emulsion chemistry, partitions are optically clear, enabling the use of a three-dimensional imaging technique to rapidly detect DNA-positive partitions. Single-molecule occupancy also allows for more straightforward multiplex assay development due to the absence of partition-specific competition. As a proof of concept, we developed a 222-plex UltraPCR assay and demonstrated its potential use as a rapid, low-cost screening assay for noninvasive prenatal testing for as low as 4% trisomy fraction samples with high precision, accuracy, and reproducibility.

Sustainable palm weevil farming as nutrition supplementation at maternity waiting homes in Liberia.

BACKGROUND: Food insecurity is a global health challenge exacerbated by COVID-19. In Liberia, two-thirds of pregnant women are anemic, one-third of children are stunted, and 70% of households experienced food insecurity due to COVID-19. Edible insects are a nutritious, environmentally responsible, and cost-effective dietary supplement used throughout sub-Saharan Africa. Rearing palm weevil insects at maternity waiting homes (MWHs)-residential dwellings near hospitals where pregnant women await childbirth and receive postpartum services-could serve as a nutritious supplement for expectant mothers in Liberia and provide an income generating activity for MWHs. METHODS: Following a one-day training, sixteen participants established palm weevil rearing sites at four MWHs in Liberia. Pre- and post-knowledge scores were assessed immediately prior to and following training. Pre-and post-knowledge scores were analyzed using paired t-test. Participants tracked two palm weevil rearing cycles (four months), using harvest amounts, turnover, barriers to implementation, and income generated as metrics. The number of women attending MWHs was recorded throughout the study period (July-December 2020). RESULTS: Sixteen participants from four MWHs completed the training and two rearing cycles (four months) successfully. All participants showed statistically significant increases in knowledge scores following the one-day workshop with a pre-test score of 2.31 and post-test score of 7.75 out of 10 (p < 0.001). Over the 6-month study, 217 women stayed in four MWHs. Larval production from the various rearing centers ranged from 120 to 721 larvae, with all four sites producing enough palm weevil to sustain MWH residents who desired to consume the insects. One site successfully commercialized its harvest to sell approximately 50% for a total of 2,000 LD (13 USD) in income. Three of the four sites continued edible insect production beyond the four-month study period. CONCLUSIONS: An edible insect project using palm weevil larva is one promising intervention as a nutrition supplement for expectant mothers at pre-established MWHs in rural Liberia. Edible insect rearing also has potential as an income generating activity for MWHs. Future studies should focus on addressing common barriers of remote implementation and metric tracking during the COVID-19 pandemic and reinforcing infrastructure to protect larvae rearing supplies.

O-GlcNAcylation regulates dopamine neuron function, survival and degeneration in Parkinson disease.

The dopamine system in the midbrain is essential for volitional movement, action selection, and reward-related learning. Despite its versatile roles, it contains only a small set of neurons in the brainstem. These dopamine neurons are especially susceptible to Parkinson's disease and prematurely degenerate in the course of disease progression, while the discovery of new therapeutic interventions has been disappointingly unsuccessful. Here, we show that O-GlcNAcylation, an essential post-translational modification in various types of cells, is critical for the physiological function and survival of dopamine neurons. Bidirectional modulation of O-GlcNAcylation importantly regulates dopamine neurons at the molecular, synaptic, cellular, and behavioural levels. Remarkably, genetic and pharmacological upregulation of O-GlcNAcylation mitigates neurodegeneration, synaptic impairments, and motor deficits in an animal model of Parkinson's disease. These findings provide insights into the functional importance of O-GlcNAcylation in the dopamine system, which may be utilized to protect dopamine neurons against Parkinson's disease pathology.

Financial Preparedness for Birth Among Rural Zambian Women: Do Antenatal Care Contacts Make a Difference?

INTRODUCTION: Financial constraints are one of the biggest barriers for women of low-income countries to receive necessary reproductive health services. Educating women about the importance of saving money has been incorporated as a component of antenatal care (ANC) contacts, but little is known whether ANC contacts influence women's saving. METHODS: A secondary analysis was conducted on data from a cross-sectional household survey study of 1109 women who recently gave birth in two rural districts of Zambia. RESULTS: Receiving ANC contacts early and often and discussing saving money during ANC were associated with saving money for the mother's birth, but not with saving enough money for the most recent birth. DISCUSSION: Continued effort is needed to encourage women to attend ANC contacts earlier and more frequently. Additionally, the importance of saving money for birth should be discussed during ANC contacts. Future studies need to explore why women's action in saving does not necessarily lead to saving enough for childbirth.

Effect of gintonin on matrix metalloproteinase-9 concentration in tears during corneal wound healing in rabbits.

It has been shown that gintonin, isolated from Panax ginseng, can promote rapid corneal wound healing. We aimed to elucidate the underlying mechanism and investigated whether gintonin affects the concentration of the extracellular matrix remodelling factor matrix metalloproteinase-9 (MMP-9) in tears during rabbit corneal wound healing in vivo. Twelve eyes (six rabbits) were divided equally into three groups. All eyes underwent corneal de-epithelialisation. The control group received Tearin Free sodium hyaluronate 0.1%, the solcoseryl group received solcoseryl-120 concentrate, and the gintonin group received 2.5 mg gintonin in sodium hyaluronate 0.1%. All preparations were administered for 5 days and the concentration of MMP-9 was measured in tears via ELISA on days 0, 1, and 5. MMP-9 concentrations in all groups were increased at day 1 and reduced at day 5. Of note, we found a significant change over the time frame for the gintonin group (P < 0.05) but not for the control or solcoseryl groups (P > 0.05) Moreover, increased MMP-9 levels between days 0 and 1, and their reduction between days 1 and 5, were significant in the gintonin group compared to those in the other groups (P < 0.05); however, and once more, these changes were not significant between the control and solcoseryl groups (P > 0.05). In conclusion, gintonin increases the concentration of MMP-9 rapidly within a day of injury, and decreasing it thereafter.

Sequential Connection of Mutually Exclusive Catalytic Reactions by a Method Controlling the Presence of an MOF Catalyst: One-Pot Oxidation of Alcohols to Carboxylic Acids.

A functionalized metal-organic framework (MOF) catalyst applied to the sequential one-pot oxidation of alcohols to carboxylic acids controls the presence of a heterogeneous catalyst. The conversion of alcohols to aldehydes was acquired through aerobic oxidation using a well-known amino-oxy radical-functionalized MOF. In the same flask, a simple filtration of the radical MOF with mild heating of the solution completely altered the reaction media, providing radical scavenger-free conditions suitable for the autoxidation of the aldehydes formed in the first step to carboxylic acids. The mutually exclusive radical-catalyzed aerobic oxidation (the first step with MOF) and radical-inhibited autoxidation (the second step without MOF) are sequentially achieved in a one-pot manner. Overall, we demonstrate a powerful and efficient method for the sequential oxidation of alcohols to carboxylic acids by employing a readily functionalizable heterogeneous MOF. In addition, our MOF in-and-out method can be utilized in an environmentally friendly way for the oxidation of alcohols to carboxylic acids of industrial and economic value with broad functional group tolerance, including 2,5-furandicarboxylic acid and 1,4-benzenedicarboxylic acid, with good yield and reusability. Furthermore, MOF-TEMPO, as an antioxidative stabilizer, prevents the undesired oxidation of aldehydes, and the perfect "recoverability" of such a reactive MOF requires a re-evaluation of the advantages of MOFs from heterogeneity in catalytic and related applications.

Semantic Segmentation of White Matter in FDG-PET Using Generative Adversarial Network.

In the diagnosis of neurodegenerative disorders, F-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is used for its ability to detect functional changes at early stages of disease process. However, anatomical information from another modality (CT or MRI) is still needed to properly interpret and localize the radiotracer uptake due to its low spatial resolution. Lack of structural information limits segmentation and accurate quantification of the 18F-FDG PET/CT. The correct segmentation of the brain compartment in 18F-FDG PET/CT will enable the quantitative analysis of the 18F-FDG PET/CT scan alone. In this paper, we propose a method to segment white matter in 18F-FDG PET/CT images using generative adversarial network (GAN). The segmentation result of GAN model was evaluated using evaluation parameters such as dice, AUC-PR, precision, and recall. It was also compared with other deep learning methods. As a result, the proposed method achieves superior segmentation accuracy and reliability compared with other deep learning methods.

Implementation of Healthy Men Healthy Communities: A Health Promotion and Gender-Based Violence Prevention Program for Male South Sudanese Refugees in Uganda.

Men living in refugee settings are often exposed to violence, poverty, and social instability, which impacts physical and mental health and increases the risk of perpetrating sexual and gender-based violence. Healthy Men Healthy Communities was developed as a male-led health promotion program to address men's physical and mental health and their role in creating healthy relationships and families. Three community leaders from the settlements were trained to facilitate the program, which was implemented among six groups consisting of twelve men in each group. Pre/post surveys and feedback were collected among the facilitators and participants. Facilitators suggested culturally appropriate ways to present physical activities as a stress reduction technique and the importance of spacing out births. The small group setting facilitated open conversations on topics such as birth spacing and healthy partner communication. Participants experienced an increase in knowledge and confidence in practicing the program content, such as stress-reduction techniques and healthy communication strategies. Participants recommended additional topics such as fertility and sexually transmitted infections. The Healthy Men Healthy Communities program has the potential for wider implementation among male South Sudanese refugees to promote their health as well as the health of their families.

Changes in Adolescent Health Behavior and the Exacerbation of Economic Hardship During the COVID-19 Pandemic: A Cross-sectional Study From the Korea Youth Risk Behavior Survey.

OBJECTIVES: This study investigated the association between exacerbated economic hardship during the coronavirus disease 2019 (COVID-19) pandemic and changes in the health behaviors of Korean adolescents. METHODS: We analyzed data from the 2021 Korea Youth Risk Behavior Survey and included 44 908 students (22 823 boys and 22 085 girls) as study subjects. The dependent variables included changes in health behaviors (breakfast habits, physical activity, and alcohol use) that occurred during the COVID-19 pandemic. The aggravation of economic hardship by COVID-19 and the subjective economic status of the family were used as exposure variables. Multiple logistic regression analysis was utilized to calculate the prevalence odds ratios (PORs). RESULTS: Severe exacerbation of a family's economic hardship due to COVID-19 was negatively associated with the health behaviors of adolescents, including increased breakfast skipping (POR, 1.85; 95% confidence interval [CI], 1.55 to 2.21 for boys and POR, 1.56; 95% CI, 1.27 to 1.92 for girls) and decreased physical activity (POR, 1.37; 95% CI, 1.19 to 1.57 for boys and POR, 1.38; 95% CI, 1.19 to 1.60 for girls). These negative changes in health behaviors were further amplified when combined with a low subjective family economic status. CONCLUSIONS: The experience of worsening household hardship can lead to negative changes in health behavior among adolescents. It is crucial to implement measures that address the economic challenges that arise from stressful events such as COVID-19 and to strive to improve the lifestyles of adolescents under such circumstances.

Skin benefits of postbiotics derived from Micrococcus luteus derived from human skin: an untapped potential for dermatological health.

BACKGROUND: The skin microbiome, a diverse community of microorganisms, plays a crucial role in maintaining skin health. Among these microorganisms, the gram-positive bacterium Micrococcus luteus exhibits potential for promoting skin health. This study focuses on postbiotics derived from M. luteus YM-4, a strain isolated from human skin. OBJECTIVE: Our objective is to explore the beneficial effects of YM-4 culture filtrate on dermatological health, including enhancing barrier function, modulating immune response, and aiding recovery from environmental damage. METHODS: The effects of the YM-4 culture filtrate were tested on human keratinocytes and fibroblasts under various conditions using real-time PCR for gene expression analysis and fibroblast migration assays. A dehydration-simulated model was employed to prepare RNA-Seq samples from HaCaT cells treated with the YM-4 culture filtrate. Differentially expressed genes were identified and functionally classified through k-means clustering, gene ontology terms enrichment analyses, and protein-protein interactions mapping. RESULTS: The YM-4 culture filtrate enhanced the expression of genes involved in skin hydration, hyaluronic acid synthesis, barrier function, and cell proliferation. It also reduced inflammation markers in keratinocytes and fibroblasts under stress conditions. It mitigated UVB-induced collagen degradation while promoted collagen synthesis, suggesting anti-aging properties, and accelerated wound healing processes by promoting cell proliferation and migration. RNA sequencing analysis revealed that the YM-4 culture filtrate could reverse dehydration-induced transcriptional changes towards a state similar to untreated cells. CONCLUSION: M. luteus YM-4 culture filtrate exhibits significant therapeutic potential for dermatological applications.

The use of a mobile obstetric emergency system to improve obstetric referrals in Bong County, Liberia: A pre-post study.

OBJECTIVE: Liberia experiences an unmet need for cesarean section with about 5% population coverage, lower than 9%-19% coverage associated with improved maternal and newborn outcomes. Delays in the referral process for comprehensive emergency obstetric and newborn care (CEmONC) services due to ineffective communication between a rural health facility (RHF) and a district hospital contribute to the low CS rate. This study examined the association between mobile obstetric emergency system (MORES) implementation and referral time for obstetric emergencies as well as maternal/newborn outcomes. METHODS: A pre-post descriptive analysis was conducted on data collected from 20 rural health facilities (RHFs) and two hospitals in Bong County. Women with referral data from both RHFs and hospitals were matched and information including transfer time, reasons for referral, and maternal and newborn outcomes were extracted. Descriptive analysis and logistic regression models examined the relationship between the intervention's implementation and mode of delivery, maternal outcome, newborn outcome, and transfer time from RHF to district hospital. Ethics approval was obtained from two study centers. RESULTS: Women had higher odds of undergoing a CS at endline (OR: 1.86 95% CI: 0.99-3.46) compared to baseline. Additionally, newborns had lower odds of showing non-vigorous symptoms (OR: 0.31; 95% CI: 0.14-0.68), defined as a newborn with poor respiratory effort, muscle tone, or heart rate. There was no significant association between the intervention's implementation and transfer time. CONCLUSION: The MORES intervention is a promising means to increase timely care seeking along the referral pathway which may enhance access to cesarean section as well as improved newborn outcome in low- and middle-income countries.

Comparative whole genome analysis of face-derived Streptococcus infantis CX-4 unravels the functions related to skin barrier.

BACKGROUND: The skin microbiome is essential in guarding against harmful pathogens and responding to environmental changes by generating substances useful in the cosmetic and pharmaceutical industries. Among these microorganisms, Streptococcus is a bacterial species identified in various isolation sources. In 2021, a strain of Streptococcus infantis, CX-4, was identified from facial skin and found to be linked to skin structure and elasticity. As the skin-derived strain differs from other S. infantis strains, which are usually of oral origin, it emphasizes the significance of bacterial variation by the environment. OBJECTIVE: This study aims to explore the unique characteristics of the CX-4 compared to seven oral-derived Streptococcus strains based on the Whole-Genome Sequencing data, focusing on its potential role in skin health and its possible application in cosmetic strategies. METHODS: The genome of the CX-4 strain was constructed using PacBio Sequencing, with the assembly performed using the SMRT protocol. Comparative whole-genome analysis was then performed with seven closely related strains, utilizing web-based tools like PATRIC, OrthoVenn3, and EggNOG-mapper, for various analyses, including protein association analysis using STRING. RESULTS: Our analysis unveiled a substantial number of Clusters of Orthologous Groups in diverse functional categories in CX-4, among which sphingosine kinase (SphK) emerged as a unique product, exclusively present in the CX-4 strain. SphK is a critical enzyme in the sphingolipid metabolic pathway, generating sphingosine-1-phosphate. The study also brought potential associations with isoprene formation and retinoic acid synthesis, the latter being a metabolite of vitamin A, renowned for its crucial function in promoting skin cell growth, differentiation, and maintaining of skin barrier integrity. These findings collectively suggest the potential of the CX-4 strain in enhancing of skin barrier functionality. CONCLUSION: Our research underscores the potential of the skin-derived S. infantis CX-4 strain by revealing unique bacterial compounds and their potential roles on human skin.

HPK1 Dysregulation-Associated NK Cell Dysfunction and Defective Expansion Promotes Metastatic Melanoma Progression.

Distant metastasis, the leading cause of cancer death, is efficiently kept in check by immune surveillance. Studies have uncovered peripheral natural killer (NK) cells as key antimetastatic effectors and their dysregulation during metastasis. However, the molecular mechanism governing NK cell dysfunction links to metastasis remains elusive. Herein, MAP4K1 encoding HPK1 is aberrantly overexpressed in dysfunctional NK cells in the periphery and the metastatic site. Conditional HPK1 overexpression in NK cells suffices to exacerbate melanoma lung metastasis but not primary tumor growth. Conversely, MAP4K1-deficient mice are resistant to metastasis and further protected by combined immune-checkpoint inhibitors. Mechanistically, HPK1 restrains NK cell cytotoxicity and expansion via activating receptors. Likewise, HPK1 limits human NK cell activation and associates with melanoma NK cell dysfunction couples to TGF-ß1 and patient response to immune checkpoint therapy. Thus, HPK1 is an intracellular checkpoint controlling NK-target cell responses, which is dysregulated and hijacked by tumors during metastatic progression.