Detection of MicroRNA-155 based on lambda exonuclease selective digestion and CRISPR/cas12a-assisted amplification.

In numerous malignancies, miRNA-155 is overexpressed and has oncogenic activity because it is one of the most efficient microRNAs for inhibiting apoptosis in human cancer cells. As a result, the highest sensitive detection of the miRNA-155 gene is a technological instrument that can enable early cancer screening. In this study, a miRNA-155 biosensor was created to create a hairpin probe that can bind to the miRNA-155 gene using lambda nucleic acid exonuclease, which can cut the 5' phosphorylated double strand, and by the DNA probe is recognized by the Cas12a enzyme, which then activates Cas12a to catalyze trans-cutting produces strong fluorescence. Research finding, the target concentration's logarithm and corresponding fluorescence intensity have a strong linear connection, and the limit of detection (LOD) of the sensing system was determined to be 8.3 pM. In addition, the biosensor displayed exceptional specificity, low false-positive signal, and high sensitivity in detecting the miRNA-155 gene in serum samples. This study's creation of a biosensor that has high sensitivity, good selectivity, and is simple to operate provides promising opportunities for research into biosensor design and early cancer detection.

Characteristic cembrane-type diterpenoids with nitric oxide inhibitory activity from the gum resin of Boswellia carterii Birdw.

Five new characteristic cembrane-type diterpenoids (olibacartiols A-E, 1-5) were acquired from the gum resin of Boswellia carterii. The structures of these diterpenoids were characterized by detailed spectroscopic analysis, and compounds 1-3 were unambiguously confirmed by single-crystal X-ray diffraction experiments. The anti-inflammatory activities of the isolated compounds were evaluated using LPS-induced BV2 cell model and compounds 2-5 showed moderate NO inhibitory effects with IC50 values of 8.84 ± 1.02, 9.82 ± 1.95, 9.75 ± 2.24, and 7.39 ± 1.24 µM, respectively.

The safety of benzodiazepines and related drugs during pregnancy: an updated meta-analysis of cohort studies.

PURPOSE: The prevalence of benzodiazepines and related drugs (BZRDs) use during pregnancy increased sharply in recent years. Thus, there are concerns regarding the pregnancy outcomes following exposure to BZRDs. METHODS: Two electronic databases were thoroughly searched to identify related clinical studies published from inception until June 2023. English-language cohort studies with high-quality comparing antenatal BZRDs exposure to an unexposed group on any delivery outcome were included. RESULTS: Ten cohort studies that estimated adverse neonatal outcomes associated with exposure to BZRDs during pregnancy were included. Exposure to BZRDs during pregnancy was associated with an increased risk of congenital malformation [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.05-1.13, p < 0.001], heart malformation (OR 1.13, 95% CI 1.04-1.22, p = 0.003), preterm birth (OR 1.45, 95% CI 1.23-1.7, p < 0.001), SGA (OR 1.18, 95% CI 1.08-1.29, P < 0.001), LBW (OR 1.42, 95% CI 1.25-1.6, p = 0.001) or low Apgar score (OR 1.42, 95% CI 1.08-1.87, p = 0.011),compared with no exposure. Further analyses limited to the first trimester exposure yielded consistent results. CONCLUSIONS: Exposure to BZRDs during pregnancy may be associated with several adverse neonatal outcomes. However, we could not rule out the potential indication confounding factor, further studies with high-quality that control for important confounders are still needed to verify our findings.

miR-15a-5p up-regulates TLR4 and induces the formation of hypertrophic scars and keloids.

The formation of hypertrophic scar and keloid is considered to be a very complex pathological process. Our previous studies have shown that miR-15a-5p is an important miRNA in HTS tissues, and its expression level is significantly increased. Therefore, the potential mechanism of action of miR-15a-5p in scarring arouses our interest. This study preliminarily investigated the expression level of miR-15a-5p in HTS tissue and normal skin tissue and further explored the molecular mechanism. The results of this study once again confirmed that the expression level of miR-15a-5p was increased in HTS tissues and cells, and the closely related mRNA and protein levels of MyD88 and TGF-ß were also highly expressed. The relative expression levels of fibrosis-related indicators in HTsFb cells were up-regulated, such as collagen-Ⅰ, collagen-III and α-SMA. We constructed the HTS cell model and BALB/c nude animal model, and down-regulating miR-15a-5p, the HTsFb cells proliferation was inhibited, and qRT-PCR results showed that the fibrosis index mRNA was also reduced, and significantly reduce the pathological state of scar tissue. In conclusion, miR-15a-5p may participate in the formation and development of HTS through TLR/MyD88 signaling pathway and TGF-ß1 signaling pathway.

Lindenane sesquiterpenoid monomers and oligomers: Chemistry and pharmacological activities.

Lindenane sesquiterpenoid monomers and oligomers, characterized by a sterically congested cyclopentane and an unusual trans-5/6 ring junction, are mainly found in Chloranthaceae species and the genus Lindera Thunb (Lauraceae). Numerous studies have shown that lindenane sesquiterpenoid monomers and oligomers exhibit a broad range of biological activities, such as cytotoxicity, anti-inflammation, neuroprotection, antifungal, and anti-malarial activities. This review covers publications from the first identification of lindeneol in 1925-2023 and classifies the lindenane sesquiterpenoid derivatives into sesquiterpenoid monomers, sesquiterpenoid-monoterpene conjugates, sesquiterpenoid homodimers, sesquiterpenoid heterodimers, and trimeric sesquiterpenoids. In addition, their biological activities are summarized. This review will establish a scientific basis and provide guidance for utilizing this unique class of natural products as potential lead compounds to develop their application in treating diseases corresponding to inflammation, cancer, and plasmodium.

A Study on the Through-Plane Permeability of Anisotropic Fibrous Porous Material by Fractal Stochastic Method.

The through-plane permeability is of great importance for understanding the transport phenomenon in anisotropic fibrous porous material. In this paper, a novel pore-scale model based on the equilateral triangle representative unit cell (RUC) and capillary bundle model is developed for the fluid flow through the anisotropic fibrous porous material according to fractal theory, and the effective through-plane permeability is presented accordingly. The digital structures of the fibrous porous material are generated by a fractal stochastic method (FSM), and the single-phase fluid flow through the 3D-reconstructed model is simulated by using the finite element method (FEM). It was found that the effective through-plane permeability depends on the fiber column size, porosity, and fractal dimensions for pore and tortuosity. The results show that the predicted through-plane permeability by the present fractal model indicates good agreement with numerical results and available experimental data as well as empirical formulas. The dimensionless through-plane permeability is positively correlated with the porosity and negatively correlated with the fractal dimensions for pore and tortuosity at certain porosity.

Effects of icariin on alleviating schizophrenia-like symptoms by regulating the miR-144-3p/ATP1B2/mTOR signalling pathway.

Schizophrenia is a group of severe mental disorders. Icariin is a main active component of Epimedium, possessing therapeutic effects on various neurodegenerative diseases. The present study investigated whether icariin is effective in alleviating schizophrenia-like symptoms and explored its underlying molecular mechanism. A developmental schizophrenia rat model employing 2-week repeated MK-801 administration was established. Icariin was orally administrated 3 time per day for 2 weeks after the MK-801 administration. Open-field test (OFT), novel object recognition (NOR), rotarod, and Morris water maze (MWM) were performed to examine the therapeutic effects of icariin on behavioural abnormalities. Hematoxylin-eosin (HE) staining on hippocampus slices, and MTT assay and Calcein/PI staining on the SK-N-SH cells treated with MK-801 were carried out to assess the neuroprotective effects of icariin. Furthermore, the regulation of icariin on the miR-144-3p/ATP1B2/mTOR signalling pathway was examined by RT-PCR and Western blots. The results showed that icariin alleviated MK-801-induced anxiety and recognition memory deficits in the OFT and NOR, respectively. Additionally, weakened motor coordination caused by MK-801 was restored by icariin. The MWM test also showed that icariin can improve MK-801-induced impaired spatial memory and swimming ability. Furthermore, brain grey matter atrophy, cytotoxicity, and cell apoptosis caused by MK-801 can be eliminated by icariin. Lastly, icariin can regulate the expression of miR-144-3p and ATP1B2, and enhance the phosphorylation of PI3K, Akt, and mTOR. In conclusion, this study revealed that icariin may have therapeutic effects on schizophrenia-like disorders via regulating the miR-144-3p/ATP1B2/mTOR signalling, suggesting that icariin has potential to become an antipsychotic drug.

A Pax-5a gene analysis approach enabled by selective digestion with lambda exonuclease.

Owing to the rapid increase in acute leukemia patients, the detection of Pax-5a, which is a tumor marker, is very important for the early diagnosis of patients. Therefore, by combining the selective digestion function of lambda exonuclease and the hybridization chain reaction (HCR) enzyme-free amplification system, we design a biosensor to detect the Pax-5a gene with high sensitivity. Lambda exonuclease can cleave the blunt end formed by the hairpin probe and the Pax-5a gene, which exposes the nucleic acid sequence that can initiate the HCR. When the HCR is triggered, the fluorophore and quencher on H1 and H2 move away from each other, so that the fluorescence signal of the quenched fluorophore can be recovered. Under optimal experimental conditions, a good linear relationship was established between the fluorescence intensity and the logarithm of the target concentration, and the limit of detection (LOD) of Pax-5a was calculated to be 7.6 pM. In addition, the biosensor can not only discriminate the base mismatch sequences of the Pax-5a gene, but also be suitable for target detection in complex human serum samples. Therefore, this biosensor, with the advantages of simple operation, high sensitivity, and good selectivity, has a good application prospect and guiding role in the diagnosis of acute B lymphocytic leukemia and the design of biosensors.

Effect and attributable burden of hot extremes on bacillary dysentery in 31 Chinese provincial capital cities.

BACKGROUND: High atmospheric temperature has been associated with the occurrence of bacillary dysentery (BD). Recent studies have suggested that hot extremes may influence health outcomes, however, none have examined the association between hot extremes and BD risk, especially at the national level. OBJECTIVES: To assess the effect and attributable burden of hot extremes on BD cases and to identify populations at high risk of BD. METHODS: Daily incident BD data of 31 provincial capital cities from 2010 to 2018 were collected from the Chinese Center for Disease Control and Prevention, weather data was obtained from the fifth generation of the European Re-Analysis Dataset. Three types of hot extremes, including hot day, hot night, and hot day and night, were defined according to single or sequential occurrence of daytime hot and nighttime hot within 24 h. A two-stage analytical strategy combined with distributed lag non-linear models (DLNM) was used to evaluate city-specific associations and national pooled estimates. RESULTS: Hot extremes were significantly associated with the risk of BD on lagged 1-6 days. The overall cumulative relative risk (RR) was 1.136 [95% confidence interval (CI): 1.022, 1.263] for hot day, 1.181 (95% CI: 1.019, 1.369) for hot night, and 1.154 (95% CI: 1.038, 1.283) for hot day and night. Northern residents, females, and children younger than or equal to 14 years old were vulnerable under hot night, southern residents were vulnerable under hot day, and males were vulnerable under hot day and night. 1.854% (95% CI: 1.294%, 2.205%) of BD cases can be attributable to hot extremes, among which, hot night accounted for a large proportion. CONCLUSIONS: Hot extremes may significantly increase the incidence risk and disease burden of BD. Type-specific protective measures should be taken to reduce the risk of BD, especially in those we found to be particularly vulnerable.

Gender Differences in Transnational Brand Purchase Decision Toward Mixed Culture and Original Culture Advertisements: An fNIRS Study.

Culture strategy is very important for transnational brand marketing. Functional near-infrared spectroscopy (fNIRS) is a promising brain imaging modality for neuromarketing research. In the present study, we used fNIRS to explore the neural correlates of consumers' purchase decision on different cross-culture marketing strategies. Forty Chinese participants watched transnational brands and products advertised with photographs of the brands' original culture (the original culture advertisements) and advertised with photographs of Chinese culture (the mixed culture advertisements), respectively. The behavioral results showed that the female participants showed significantly higher purchase rate when watching the original culture advertisements than the mixed culture advertisements, whereas the male participants did not show significant preference between these two types. The fNIRS results further revealed that for the female participants, watching mixed culture advertisements evoked significant positive activation in the left dorsolateral prefrontal cortex and negative activation in the medial prefrontal cortex, which was not found in the male participants. These findings suggest possible cognitive and emotional differences between men and women in purchase decision making toward different cross-culture marketing strategy. The present study also demonstrates the great potential of fNIRS in neuromarketing research.

Meta-analysis found that studies may have overestimated Caesarean section risks for attention-deficit hyperactivity disorder by ignoring confounding factors.

AIM: Epidemiological studies on associations between Caesarean sections (C-sections) and attention-deficit hyperactivity disorder (ADHD) have been inconsistent, and we performed a meta-analysis. METHODS: We systematically searched PubMed and Embase to December 2018 and included nine hospital-based and population registry studies published in 2011-2018. These covered a total study cohort of more than 2.5 million people in eight countries: Australia, Brazil, Denmark, Finland, Germany, Sweden, Turkey and the UK. The analysis provided summary odds ratios (ORs) and 95% confidence intervals (CI) while taking heterogeneity into account. RESULTS: We found that that C-sections were associated with a small increase in the risk of ADHD (OR 1.14, 95% CI 1.11, 1.17, I2 0%) in offspring. In subgroup analyses, the association remained for both infants born after elective C-sections (OR, 1.15, 1.11, 1.19, I2 0%) and emergency C-sections (OR, 1.13, 1.1, 1.17, I2 45.4%). However, these were only marginally significant when we pooled data from siblings from other pregnancies (OR, 1.06, 1.00-1.13, I2 0%), implying that the association was due to confounding. CONCLUSION: The statistically significant association between C-sections and ADHD in children can be partially explained by unmeasured confounding. Further research controlling for important confounders is required before firm conclusions can be drawn.

Group cognitive-behavioral therapy in insomnia: a cross-sectional case-controlled study.

BACKGROUND: Group cognitive-behavioral therapy (GCBT) might meet the considerable treatment demand of insomnia, but its effectiveness needs to be addressed. PARTICIPANTS: This study recruited 27 insomnia patients treated with 16-weeks of zolpidem (zolpidem group), 26 patients treated with 4-weeks of zolpidem and also treated with 12-weeks of GCBT (GCBT group), and 31 healthy control volunteers. METHODS: Before treatment and 16 weeks after intervention, participants were evaluated using the Patient Health Questionnaires (Patient Health Questionnaire-9 [PHQ-9] and Patient Health Questionnaire-15 [PHQ-15]), the Dysfunctional Beliefs and Attitudes about Sleep-16 (DBAS-16), and the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Compared to the zolpidem and healthy control groups, the scale scores of PHQ-9, PHQ-15, DBAS-16 and PSQI were significantly reduced after intervention in the GCBT group. Regarding the score changes, there were correlations between PSQI, DBAS-16, PHQ-9, and PHQ-15 scales in the zolpidem group, but there were limited correlations between PSQI and some DBAS-16 scales in the GCBT group. CONCLUSION: Our results indicate that GCBT is effective to treat insomnia by improving sleep quality and reducing emotional and somatic disturbances; thus, the study supports the advocacy of applying group psychotherapy to the disorder.

[Regulation action and nerve electrophysiology mechanism of acupuncture on arousal state in patients of primary insomnia].

OBJECTIVE: To compare the difference between acupuncture and estazolam on arousal state in patients of primary insomnia, and to explore its nerve electrophysiology mechanism. METHODS: Sixty-four patients of primary insomnia were randomized into an acupuncture group (32 cases) and a medication group (32 cases). After 3 patients were excluded, 31 cases in the acupuncture group and 30 cases in the medication group were included. Patients in the acupuncture group were treated with acupuncture at Sishencong (EX-HN 1), Anmian (Extra), Shenmen (HT 7), Sanyinjiao (SP 6), Zhaohai (KI 6), Shenmai (BL 62) as main acupoints, combined with supporting acupoints, once a day, five times per week, continuously for 4 weeks. Patients in the medication group were treated with oral administration of estazolam, once a day, continuously for 4 weeks. The Pittsburgh sleep quality index (PSQI) and mean sleep latency (MSL) of multiple sleep latency test (MSLT) were compared before and after treatment in the two groups; the polysomnography (PSG) was applied to monitor the indices regarding sleep structure. RESULTS: Compared before treatment, PSQI score was reduced after treatment in the two groups (both P<0.01), which was more significant in the acupuncture group (P<0.05). Compared before treatment, sleep onset latency (SOL), number of awakenings (NWAK) and wake after sleep onset (WASO) were reduced, while total sleep time (TST) and sleep efficiency (SE) were significantly increased in the two groups after treatment (all P<0.01). Compared before treatment, the percentage of non-rapid eye movement period 1/2/3 (N1, N2, N3) and the percentage of rapid eye movement period (REM) to TST were not significantly changed after treatment in the medication group (all P>0.05). Compared before treatment, the percentage of N1, N2 to TST was reduced, while the percentage of N3 and REM to TST was increased after treatment in the acupuncture group (P<0.01). The SOL, NWAK, WASO, TST, SE were not statistically changed after treatment in each group (all P>0.05). Compared with the medication group, the percentage of N1 and N2 was reduced while that of N3 and REM was increased after treatment in the acupuncture group (all P<0.01). After treatment, MSL of MSLT were obviously decreased in the two groups (both P<0.01), which were more significant in the acupuncture group (P<0.05). CONCLUSIONS: Acupuncture can more effectively improve sleep quality of primary insomnia than estazolam, and is more beneficial for regulation of hyperarousal state.

Antidepressant use during pregnancy and risk of postpartum hemorrhage: A systematic review and meta-analysis.

Evidence about relationship between antidepressant use during pregnancy and the risk of postpartum hemorrhage (PPH) is conflicting. The aim of this meta-analysis was to systematically assess this relationship. To identify relevant studies, we conducted systematic searches in PubMed and Embase of articles published through May 2016. Random-effects models were adopted to estimate overall relative risk. In total, eight studies involving more than 40,000 PPH cases were included in our meta-analysis. After pooling the estimates, the odds for developing PPH were 1.32-fold higher (risk ratio, RR = 1.32; 95% confidence interval, CI = 1.17-1.48) in antidepressant users compared with individuals who had not taken antidepressants. In subgroup analyses, the associations still exist for women with exposure to non-SRI (RR = 1.31, 95% CI = 1.1-1.56), SRIs (RR = 1.23, 95% CI = 1.06-1.44), SSRIs (RR = 1.2, 95% CI = 1.04-1.38), and SNRIs (RR = 1.62, 95% CI = 1.41-1.85). Based on exposure window, we found an increased risk of PPH among current (RR = 1.37, 95% CI = 1.09-1.71) and recent users (RR = 1.32, 95% CI = 1.15-1.51), but not past users (RR = 1.08, 95% CI = 0.88-1.31). The findings of this meta-analysis support an increased risk of PPH in women exposure to antidepressant during late gestation.

Maternal infection during pregnancy and risk of autism spectrum disorders: A systematic review and meta-analysis.

Conflicting evidence exists with regard to the relationship between maternal infection during pregnancy and the risk of autism spectrum disorder (ASD) in offspring. The aim of this meta-analysis was to systematically assess this relationship. To identify relevant studies, we conducted systematic searches in PubMed and Embase of scientific articles published through March 2016. Random-effects models were adopted to estimate overall relative risk. A total of 15 studies (2 cohort and 13 case-control studies) involving more than 40,000 ASD cases were included in our meta-analysis. Our results showed that maternal infection during pregnancy was associated with an increased risk of ASD in offspring (OR=1.13, 95% confidence interval (CI): 1.03-1.23), particularly among those requiring hospitalization (OR=1.30, 95% CI: 1.14-1.50). Subgroup analyses suggested that risk may be modulated by the type of infectious agent, time of infectious exposure, and site of infection. These findings indicate that maternal infection during pregnancy increases the risk of ASD in offspring. Possible mechanisms may include direct effects of pathogens and, more indirectly, the effects of inflammatory responses on the developing brain.