Microglial circ-UBE2K exacerbates depression by regulating parental gene UBE2K via targeting HNRNPU.

Background: Knowledge about the pathogenesis of depression and treatments for this disease are lacking. Epigenetics-related circRNAs are likely involved in the mechanism of depression and have great potential as treatment targets, but their mechanism of action is still unclear. Methods: Circular RNA UBE2K (circ-UBE2K) was screened from peripheral blood of patients with major depressive disorder (MDD) and brain of depression model mice through high-throughput sequencing. Microinjection of circ-UBE2K overexpression lentivirus and adeno-associated virus for interfering with microglial circ-UBE2K into the mouse hippocampus was used to observe the role of circ-UBE2K in MDD. Sucrose preference, forced swim, tail suspension and open filed tests were performed to evaluate the depressive-like behaviors of mice. Immunofluorescence and Western blotting analysis of the effects of circ-UBE2K on microglial activation and immune inflammation. Pull-down-mass spectrometry assay, RNA immunoprecipitation (RIP) test and fluorescence in situ hybridization (FISH) were used to identify downstream targets of circ-UBE2K/ HNRNPU (heterogeneous nuclear ribonucleoprotein U) axis. Results: In this study, through high-throughput sequencing and large-scale screening, we found that circ-UBE2K levels were significantly elevated both in the peripheral blood of patients with MDD and in the brains of depression model mice. Functionally, circ-UBE2K-overexpressing mice exhibited worsened depression-like symptoms, elevated brain inflammatory factor levels, and abnormal microglial activation. Knocking down circ-UBE2K mitigated these changes. Mechanistically, we found that circ-UBE2K binds to heterogeneous nuclear ribonucleoprotein U (HNRNPU) to form a complex that upregulates the expression of the parental gene ubiquitin conjugating enzyme E2 K (UBE2K), leading to abnormal microglial activation and neuroinflammation and promoting the occurrence and development of depression. Conclusions: The findings of the present study revealed that the expression of circUBE2K, which combines with HNRNPU to form the circUBE2K/HNRNPU complex, is increased in microglia after external stress, thus regulating the expression of the parental gene UBE2K and mediating the abnormal activation of microglia to induce neuroinflammation, promoting the development of MDD. These results indicate that circ-UBE2K plays a newly discovered role in the pathogenesis of depression.

Updated Surveillance Metrics and History of the COVID-19 Pandemic (2020-2023) in Europe: Longitudinal Trend Analysis.

BACKGROUND: In this study, we built upon our initial research published in 2020 by incorporating an additional 2 years of data for Europe. We assessed whether COVID-19 had shifted from the pandemic to endemic phase in the region when the World Health Organization (WHO) declared the end of the public health emergency of international concern on May 5, 2023. OBJECTIVE: We first aimed to measure whether there was an expansion or contraction in the pandemic in Europe at the time of the WHO declaration. Second, we used dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we provided the historical context for the course of the pandemic in Europe in terms of policy and disease burden at the country and region levels. METHODS: In addition to the updates of traditional surveillance data and dynamic panel estimates from the original study, this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-tailed t test for whether regional weekly speed was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the sample period. RESULTS: Speed for the region had remained below the outbreak threshold for 4 months by the time of the WHO declaration. Acceleration and jerk were also low and stable. While the 1-day and 7-day persistence coefficients remained statistically significant, the coefficients were moderate in magnitude (0.404 and 0.547, respectively; P<.001 for both). The shift parameters for the 2 weeks around the WHO declaration were small and insignificant, suggesting little change in the clustering effect of cases on future cases at the time. From December 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t test of speed equal to 10 became insignificant for the first time in April 2023. CONCLUSIONS: While COVID-19 continues to circulate in Europe, the rate of transmission remained below the threshold of an outbreak for 4 months ahead of the WHO declaration. The region had previously been in a nearly continuous state of outbreak. The more recent trend suggested that COVID-19 was endemic in the region and no longer reached the threshold of the pandemic definition. However, several countries remained in a state of outbreak, and the conclusion that COVID-19 was no longer a pandemic in Europe at the time is unclear.

Updated Surveillance Metrics and History of the COVID-19 Pandemic (2020-2023) in the Middle East and North Africa: Longitudinal Trend Analysis.

BACKGROUND: This study updates the COVID-19 pandemic surveillance in the Middle East and North Africa (MENA) we first conducted in 2020 with 2 additional years of data for the region. OBJECTIVE: The objective of this study is to determine whether the MENA region meets the criteria for moving from a pandemic to endemic. In doing so, this study considers pandemic trends, dynamic and genomic surveillance methods, and region-specific historical context for the pandemic. These considerations continue through the World Health Organization (WHO) declaration of the end of the public health emergency for the COVID-19 pandemic on May 5, 2023. METHODS: In addition to updates to traditional surveillance data and dynamic panel estimates from the original study by Post et al, this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-sided t test to determine whether regional weekly speed of COVID-19 spread was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data from September 4, 2020, to May 12, 2023. RESULTS: The speed of COVID-19 spread for the region had remained below the outbreak threshold for 7 continuous months by the time of the WHO declaration. Acceleration and jerk were also low and stable. Although the 1- and 7-day persistence coefficients remained statistically significant and positive, the weekly shift parameters suggested the coefficients had most recently turned negative, meaning the clustering effect of new COVID-19 cases became even smaller in the 2 weeks around the WHO declaration. From December 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t test of the speed of spread equal to 10 became entirely insignificant from October 2022 onward. CONCLUSIONS: The COVID-19 pandemic had far-reaching effects on MENA, impacting health care systems, economies, and social well-being. Although COVID-19 continues to circulate in the MENA region, the rate of transmission remained well below the threshold of an outbreak for over 1 year ahead of the WHO declaration. COVID-19 is endemic in the region and no longer reaches the threshold of the pandemic definition. Both standard and enhanced surveillance metrics confirm that the pandemic had transitioned to endemic by the time of the WHO declaration.

Updated Surveillance Metrics and History of the COVID-19 Pandemic (2020-2023) in Latin America and the Caribbean: Longitudinal Trend Analysis.

BACKGROUND: In May 2020, the World Health Organization (WHO) declared Latin America and the Caribbean (LAC) the epicenter of the COVID-19 pandemic, with over 40% of worldwide COVID-19-related deaths at the time. This high disease burden was a result of the unique circumstances in LAC. OBJECTIVE: This study aimed to (1) measure whether the pandemic was expanding or contracting in LAC when the WHO declared the end of COVID-19 as a public health emergency of international concern on May 5, 2023; (2) use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history; and (3) provide, with a focus on prevention policies, a historical context for the course of the pandemic in the region. METHODS: In addition to updates of traditional surveillance data and dynamic panel estimates from the original study, we used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern (VOCs). We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Additionally, we conducted a 1-sided t test for whether the regional weekly speed (rate of novel COVID-19 transmission) was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the period from August 2020 to May 2023. RESULTS: The speed of pandemic spread for the region had remained below the outbreak threshold for 6 months by the time of the WHO declaration. Acceleration and jerk were also low and stable. Although the 1- and 7-day persistence coefficients remained statistically significant for the 120-day period ending on the week of May 5, 2023, the coefficients were relatively modest in magnitude (0.457 and 0.491, respectively). Furthermore, the shift parameters for either of the 2 most recent weeks around May 5, 2023, did not indicate any change in this clustering effect of cases on future cases. From December 2021 onward, Omicron was the predominant VOC in sequenced viral samples. The rolling t test of speed=10 became entirely insignificant from January 2023 onward. CONCLUSIONS: Although COVID-19 continues to circulate in LAC, surveillance data suggest COVID-19 is endemic in the region and no longer reaches the threshold of the pandemic definition. However, the region experienced a high COVID-19 burden in the early stages of the pandemic, and prevention policies should be an immediate focus in future pandemics. Ahead of vaccination development, these policies can include widespread testing of individuals and an epidemiological task force with a contact-tracing system.

In-situ detection scheme for EGFR gene with temperature and pH compensation using a triple-channel optical fiber biosensor.

An advanced multi-parameter optical fiber sensing technology for EGFR gene detection based on DNA hybridization technology is demonstrated in this paper. For traditional DNA hybridization detection methods, temperature and pH compensation can not be realized or need multiple sensor probes. However, the multi-parameter detection technology we proposed can simultaneously detect complementary DNA, temperature and pH based on a single optical fiber probe. In this scheme, three optical signals including dual surface plasmon resonance signal (SPR) and Mach-Zehnder interference signal (MZI) are excited by binding the probe DNA sequence and pH-sensitive material with the optical fiber sensor. The paper proposes the first research to achieve simultaneous excitation of dual SPR signal and Mach-Zehnder interference signal in a single fiber and used for three-parameter detection. Three optical signals have different sensitivities to the three variables. From a mathematical point of view, the unique solutions of exon-20 concentration, temperature and pH can be obtained by analyzing the three optical signals. The experimental results show that the exon-20 sensitivity of the sensor can reach 0.07 nm nM-1, and the limit of detection is 3.27 nM. The designed sensor gives a fast response, high sensitivity, and low detection limit, which is important for the field of DNA hybridization research and for solving the problems of biosensor susceptibility to temperature and pH.

Hypoxia Inhibitor Combined with Chemotherapeutic Agents for Antitumor and Antimetastatic Efficacy against Osteosarcoma.

Chemotherapy is the main treatment method for osteosarcoma in the clinic. However, drug resistance and its poor antimetastatic effects greatly limit its clinical application. In this work, dual-drug nanoparticles (NPs) containing albendazole (ABZ) and doxorubicin (DOX), named AD@PLGA-PEG NPs, were prepared to solve the problems of chemotherapeutic drug resistance and poor antimetastasis effects. Compared with free DOX, ABZ combined with DOX can increase intracellular reactive oxygen species (ROS) and induce more tumor cell apoptosis; therefore, AD@PLGA-PEG NPs produced more mitochondria-mediated oxidative stress and better apoptosis efficiency. Importantly, ABZ can also effectively inhibit the expression of hypoxia inducible factor-1α (HIF-1α) and then reduce the expression of its downstream vascular endothelial growth factor (VEGF); thus, the AD@PLGA-PEG NPs effectively inhibited tumor metastasis in vivo. Collectively, the dual-drug AD@PLGA-PEG NPs delivery system provided prominent antitumor and antimetastatic efficacy and might be a promising treatment for osteosarcoma.

Changes in the Demographic Distribution of Chicago Gun-Homicide Decedents From 2015-2021: Violent Death Surveillance Cross-sectional Study.

BACKGROUND: Homicide is one of the 5 leading causes of death in the United States for persons aged 1 to 44 years. In 2019, 75% of US homicides were by gun. Chicago has a gun-homicide rate 4 times the national average, and 90% of all homicides are by gun. The public health approach to violence prevention calls for a 4-step process, beginning with defining and monitoring the problem. Insight into the characteristics of gun-homicide decedents can help frame next steps, including identifying risk and protective factors, developing prevention and intervention strategies, and scaling effective responses. Although much is known about gun homicide because it is a long-standing, entrenched public health problem, it is useful to monitor trends to update ongoing prevention efforts. OBJECTIVE: This study aimed to use public health surveillance data and methods to describe changes in the race/ethnicity, sex, and age of Chicago gun-homicide decedents from 2015-2021, in the context of year-to-year variation and an overall increase in the city's gun-homicide rate. METHODS: We calculated the distribution of gun-related homicide deaths by 6 race/ethnicity and sex groups (non-Hispanic Black female, non-Hispanic White female, Hispanic female, non-Hispanic Black male, non-Hispanic White male, and Hispanic male), age in years, and age by age group. We used counts, percentages, and rates per 100,000 persons to describe the distribution of deaths among these demographic groups. Comparisons of means and column proportions with tests of significance set at P≤.05 were used to describe changes in the distribution of gun-homicide decedents over time by race-ethnicity-sex and age groups. The comparison of mean age by race-ethnicity-sex group is done using 1-way ANOVA with significance set at P≤.05. RESULTS: The distribution of gun-homicide decedents in Chicago by race/ethnicity and sex groups had been relatively stable from 2015 to 2021 with 2 notable exceptions: a more than doubling of the proportion of gun-homicide decedents who were non-Hispanic Black female (3.6% in 2015 to 8.2% in 2021) and an increase of 3.27 years in the mean age of gun-homicide decedents. The increase in mean age coincided with a decrease in the proportion of non-Hispanic Black male gun-homicide decedents between the ages of 15-19 and 20-24 years and, conversely, an increase in the proportion of non-Hispanic Black male gun-homicide decedents aged 25-34 years. CONCLUSIONS: The annual gun-homicide rate in Chicago had been increasing since 2015 with year-to-year variation. Continued monitoring of trends in the demographic makeup of gun-homicide decedents is necessary to provide the most relevant and timely information to help shape violence prevention efforts. We detected several changes that suggest a need for increased outreach and engagement marketed toward non-Hispanic Black female and non-Hispanic Black male individuals between the ages of 25-34 years.

Injectable rhein-assisted crosslinked hydrogel for efficient local osteosarcoma chemotherapy.

Osteosarcoma (OS) is the most common malignant tumor of the bone that affects children and adolescents, and its treatment usually involves doxorubicin hydrochloride (DOX). However, the drug resistance and side effects caused by high-dose DOX infusion greatly hinder its therapeutic effects. To achieve efficient OS treatment with low toxicity, an injectable rhein (RH)-assisted crosslinked hydrogel (PVA@RH@DOX hydrogel, PRDH) was designed, which was prepared by loading DOX and RH into a polyvinyl alcohol (PVA) solution. The cytotoxicity assay and live/dead staining results showed that the combination of RH and DOX more effectively killed OS cells, producing excellent effects at low concentrations of DOX. The wound healing and transwell test results proved that PRDH could significantly inhibit the metastasis and invasion of OS cells. PRDH showed a long-lasting antitumor effect after injection of a single dose, significantly suppressing the proliferation and metastasis of OS and achieving the strategy of a single administration for long-term treatment. Excitingly, RH facilitated hydrogel formation by assisting with PVA crosslinking. This system provides an alternative regimen and broadens the horizon for the clinical treatment of OS.

Lateral Offset Single-Mode Fiber-Based Fabry-Perot Interferometers with Vernier Effect for Hydrogen Sensing.

A high-sensitive optical fiber hydrogen (H2) sensor with Vernier effect by cascading three Fabry-Perot interferometers (FPIs) has been proposed. It is prepared by welding three sections of a single-mode fiber with a lateral offset structure and coating polydimethylsiloxane (PDMS) at the offset part to form three cascaded FPIs and generate a Vernier envelope spectrum. To realize H2 sensing, the hydrogen-sensitive material Pd/WO3 is fabricated and coated on the outside of the PDMS. Pd/WO3 will generate local heat when in contact with H2, which will cause the thermal expansion and refractive index change of PDMS and finally lead to the Vernier envelope wavelength shifting with the change of H2 concentration. Due to the Vernier effect, the H2 sensor can achieve a linear measurement sensitivity of 6.214 nm/% in the concentration range of 0-1%, which is 16.11 times that of a single FPI. The proposed H2 sensor possesses advantages of high sensitivity, easy preparation, compact structure, low cost, and easy long-distance transmission.

A network model of affective odor perception.

The affective appraisal of odors is known to depend on their intensity (I), familiarity (F), detection threshold (T), and on the baseline affective state of the observer. However, the exact nature of these relations is still largely unknown. We therefore performed an observer experiment in which participants (N = 52) smelled 40 different odors (varying widely in hedonic valence) and reported the intensity, familiarity and their affective appraisal (valence and arousal: V and A) for each odor. Also, we measured the baseline affective state (valence and arousal: BV and BA) and odor detection threshold of the participants. Analyzing the results for pleasant and unpleasant odors separately, we obtained two models through network analysis. Several relations that have previously been reported in the literature also emerge in both models (the relations between F and I, F and V, I and A; I and V, BV and T). However, there are also relations that do not emerge (between BA and V, BV and I, and T and I) or that appear with a different polarity (the relation between F and A for pleasant odors). Intensity (I) has the largest impact on the affective appraisal of unpleasant odors, while F significantly contributes to the appraisal of pleasant odors. T is only affected by BV and has no effect on other variables. This study is a first step towards an integral study of the affective appraisal of odors through network analysis. Future studies should also include other factors that are known to influence odor appraisal, such as age, gender, personality, and culture.

Voltammetric determination of tryptophan at a single-wall carbon nanotubes modified electrode.

A single-wall carbon nanotubes (SWNT)-film coated glassy carbon electrode (GCE) was described for the determination of tryptophan. In pH 2.5 Na2HPO4-citric acid buffer, tryptophan yields a well-defined and very sensitive oxidation peak at about 1.08 V at the SWNT-film coated GCE. The oxidation peak current increases greatly and the peak potential shifts toward more negative direction at the SWNT-modified GCE in contrast to that at the bare GCE. Under optimized conditions, the oxidation peak current is proportional to the concentration of tryptophan over the range from 4 x 10(-8) to 1 x 10(-5) mol/L. The detection limit is 1 x 10(-8) mol/L at 3 min of accumulation. Using the proposed method, tryptophan in the human's blood serum samples was determined.