A Case Report of Acute Bilateral Mydriasis Induced by Herbal Medication.

Ma Huang (Ephedra), a traditional herbal remedy, which contains pseudoephedrine and ephedrine, has sympathomimetic characteristics. Despite being banned by the Federal Drug Administration in 2004, it is still used for weight loss and energy boosting in some countries. A previous healthy 42-year-old woman experienced sudden blurred vision in both eyes. Her pupils were dilated to 6 mm each, showing diminished light reflex responses, and were not responsive to both 0.1% and 1% pilocarpine. The day before the onset of her symptoms she had taken a herbal supplement. The woman's herbal medicine was believed to contain ephedrine, a component found in Ma Huang. The sympathomimetic effects of this substance could potentially induce mydriasis. After discontinuing the medication, her symptoms improved over 4 days, leading to a suspicion of drug-induced bilateral mydriasis. Herbal products prescribed for weight loss, which may contain potential elements such as Ma Huang, could lead to unforeseen side effects like bilateral mydriasis, and should be appropriately highlighted.

PTK2 is a potential biomarker and therapeutic target for EGFR- or TLRs-induced lung cancer progression via the regulation of the cross-talk between EGFR- and TLRs-mediated signals.

Protein tyrosine kinase 2 (PTK2), epidermal growth factor receptor (EGFR), and toll-like receptor (TLRs) are amplified in non-small cell lung cancer (NSCLC). However, the functional and clinical associations between them have not been elucidated yet in NSCLC. By using microarray data of non-small cell lung cancer (NSCLC) tumor tissues and matched normal tissues of 42 NSCLC patients, the genetic and clinical associations between PTK2, EGFR, and TLRs were analyzed in NSCLC patients. To verify the functional association, we generated PTK2-knockout (PTK2-KO) lung cancer cells by using CRISPR-Cas9 gene editing method, and performed in vitro cancer progression assay, including 3D tumor spheroid assay, and in vivo xenografted NSG (NOD/SCID/IL-2Rγnull) mouse assay. Finally, therapeutic effects targeted to PTK2 in lung cancer in response to EGF and TLR agonists were verified by using its inhibitor (Defactinib). In summary, we identified that up-regulated PTK2 might be a reliable marker for EGFR- or TLRs-induced lung cancer progression in NSCLC patients via the regulation of the cross-talk between EGFR- and TLRs-mediated signaling. This study provides a theoretical basis for the therapeutic intervention of PTK2 targeting EGFR- or TLRs-induced lung cancer progression.

Toward the eco-friendly cosmetic cleansing assisted by the micro-bubbly jet.

While numerous types of chemical cosmetic cleansers have been presented, those with sensitive skin may still experience some irritation while using them. Moreover, the environmental issue of chemical agents has been documented repeatedly. To address these, we suggest the potential application of a micro-sized bubble-laden water jet to cleanse the cosmetics without (or less) using chemical detergents. We devised a venturi-type nozzle with a mesh and air holes capable of generating massive fine bubbles. By testing with the foundation and lip tint (known to be highly adhesive) coated on the synthetic leather and artificial skin surfaces, we measured that the cleansing performance of the bubbly jet is much better (even without the chemical agent) than the single-phase liquid jet. As a mechanism for enhanced removal, it is understood that the greater kinetic energy of the jet due to the acceleration of the effective liquid-air mixture flow and the direct bubble-cosmetic collisions play essential roles. We believe that the present results will spur the development of environment-friendly cleaning methods.

Prevalence of cancer-related fatigue based on severity: a systematic review and meta-analysis.

Cancer-related fatigue (CRF) affects therapeutic compliance and clinical outcomes including recurrence and mortality. This study aimed to comprehensively and comparatively assess the severity-based prevalence of CRF. From two public databases (PubMed and Cochrane Library), we extracted data containing information on both prevalence and severity of fatigue in cancer patients through December 2021. We conducted a meta-analysis to produce point estimates using random effects models. Subgroup analyses were used to assess the prevalence and severity by the organ/system tumor development, treatment phase, therapeutic type, sex and assessment method. A total of 151 data (57 studies, 34,310 participants, 11,805 males and 22,505 females) were selected, which indicated 43.0% (95% CI 39.2-47.2) of fatigue prevalence. The total CRF prevalence including 'mild' level of fatigue was 70.7% (95% CI 60.6-83.3 from 37 data). The prevalence of 'severe' fatigue significantly varied by organ/system types of cancer origin (highest in brain tumors 39.7% vs. lowest in gynecologic tumors 3.9%) and treatment phase likely 15.9% (95% CI 8.1-31.3) before treatment, 33.8% (95% CI 27.7-41.2) ongoing treatment, and 24.1% (95% CI 18.6-31.2) after treatment. Chemotherapy (33.1%) induced approximately 1.5-fold higher prevalence for 'severe' CRF than surgery (22.0%) and radiotherapy (24.2%). The self-reported data for 'severe' CRF was 20-fold higher than those assessed by physicians (23.6% vs. 1.6%). Female patients exhibited a 1.4-fold higher prevalence of 'severe' fatigue compared to males. The present data showed quantitative feature of the prevalence and severity of CRF based on the cancer- or treatment-related factors, sex, and perspective of patient versus physician. In the context of the medical impact of CRF, our results provide a comparative reference to oncologists or health care providers making patient-specific decision.

The demographic features of fatigue in the general population worldwide: a systematic review and meta-analysis.

Background: Fatigue is one of the most common subjective symptoms that impairs daily life and predict health-related events. This study aimed to estimate the prevalence of fatigue in the global population. Methods: PubMed and the Cochrane Library were used to search for relevant articles from inception to December 31, 2021. Studies with prevalence data of fatigue in the general population were selected and reviewed by three authors independently and cross-checked. Regarding subgroups, adults (≥18 years), minors (<18 years), and specific occupation population (participants in each study being limited to a specific occupational group), and fatigue types and severity, meta-analysis was conducted to produce point estimates and 95% confidence intervals (95% CI). Results: From the initial 3,432 studies, 91 studies accounting for 115 prevalence data points (623,624 participants) were finally selected. The prevalence of general fatigue (fatigue lasting < 6 months, or fatigue of unspecified duration) was 20.4% (95% CI, 16.7-25.0) in adults, 11.7% (95% CI, 5.2-26.6) in minors, and 42.3% (95% CI, 33.0-54.2) in specific occupations. Chronic fatigue (fatigue lasting more than 6 months) affected 10.1% (95% CI, 8.2-12.5) of adults, 1.5% (95% CI, 0.5-4.7) of minors, and 5.5% (95% CI, 1.4-21.6) of subjects in specific occupations. There was an overall female-predominant prevalence for all subgroup analyses, with a total odds ratio of 1.4 (95% CI, 1.3-1.6). Regarding the severity and presence of medical causes, the total prevalence of moderate fatigue [14.6% (95% CI, 9.8-21.8)] was 2.4-fold that of severe fatigue [6.1% (95% CI, 3.4-11.0)], while unexplained fatigue (fatigue experienced by individuals without any underlying medical condition that can explain the fatigue) was ~2.7-fold that of explained fatigue (fatigue experienced by individuals with a medical condition that can explain the fatigue); as proportion of 40.0% of physical, 8.6% of mental, and 28.4% of mixed cause. Conclusions: This study has produced the first comprehensive picture of global fatigue prevalence in the general population, which will provide vital reference data contributing to fatigue-related research, including the prevention of diseases. Systematic review registration: Identifier: CRD42021270498.

ß-arrestin 2 negatively regulates lung cancer progression by inhibiting the TRAF6 signaling axis for NF-κB activation and autophagy induced by TLR3 and TLR4.

ß-arrestin 2 (ARRB2) is functionally implicated in cancer progression via various signaling pathways. However, its role in lung cancer remains unclear. To obtain clinical insight on its function in lung cancer, microarray data from lung tumor tissues (LTTs) and matched lung normal tissues (mLNTs) of primary non-small cell lung cancer (NSCLC) patients (n = 37) were utilized. ARRB2 expression levels were markedly decreased in all 37 LTTs compared to those in matched LNTs of NSCLC patients. They were significantly co-related to enrichment gene sets associated with oncogenic and cancer genes. Importantly, Gene Set Enrichment Analysis (GSEA) between three LTTs with highly down-regulated ARRB2 and three LTTs with lowly down-regulated ARRB2 revealed significant enrichments related to toll-like receptor (TLR) signaling and autophagy genes in three LTTs with highly down-regulated ARRB2, suggesting that ARRB2 was negatively involved in TLR-mediated signals for autophagy induction in lung cancer. Biochemical studies for elucidating the molecular mechanism revealed that ARRB2 interacted with TNF receptor-associated factor 6 (TRAF6) and Beclin 1 (BECN1), thereby inhibiting the ubiquitination of TRAF6-TAB2 to activate NF-κB and TRAF6-BECN1 for autophagy stimulated by TLR3 and TLR4, suggesting that ARRB2 could inhibit the TRAF6-TAB2 signaling axis for NF-κB activation and TRAF6-BECN1 signaling axis for autophagy in response to TLR3 and TLR4. Notably, ARRB2-knockout (ARRB2KO) lung cancer cells exhibited marked enhancements of cancer migration, invasion, colony formation, and proliferation in response to TLR3 and TLR4 stimulation. Altogether, our current data suggest that ARRB2 can negatively regulate lung cancer progression by inhibiting TLR3- and TLR4-induced autophagy.

FFAR2 antagonizes TLR2- and TLR3-induced lung cancer progression via the inhibition of AMPK-TAK1 signaling axis for the activation of NF-κB.

BACKGROUND: Free fatty acid receptors (FFARs) and toll-like receptors (TLRs) recognize microbial metabolites and conserved microbial products, respectively, and are functionally implicated in inflammation and cancer. However, whether the crosstalk between FFARs and TLRs affects lung cancer progression has never been addressed. METHODS: We analyzed the association between FFARs and TLRs using The Cancer Genome Atlas (TCGA) lung cancer data and our cohort of non-small cell lung cancer (NSCLC) patient data (n = 42), and gene set enrichment analysis (GSEA) was performed. For the functional analysis, we generated FFAR2-knockout (FFAR2KO) A549 and FFAR2KO H1299 human lung cancer cells and performed biochemical mechanistic studies and cancer progression assays, including migration, invasion, and colony-formation assays, in response to TLR stimulation. RESULTS: The clinical TCGA data showed a significant down-regulation of FFAR2, but not FFAR1, FFAR3, and FFAR4, in lung cancer, and a negative correlation with TLR2 and TLR3. Notably, GSEA showed significant enrichment in gene sets related to the cancer module, the innate signaling pathway, and the cytokine-chemokine signaling pathway in FFAR2DownTLR2UpTLR3Up lung tumor tissues (LTTs) vs. FFAR2upTLR2DownTLR3Down LTTs. Functionally, treatment with propionate (an agonist of FFAR2) significantly inhibited human A549 or H1299 lung cancer migration, invasion, and colony formation induced by TLR2 or TLR3 through the attenuation of the cAMP-AMPK-TAK1 signaling axis for the activation of NF-κB. Moreover, FFAR2KO A549 and FFAR2KO H1299 human lung cancer cells showed marked increases in cell migration, invasion, and colony formation in response to TLR2 or TLR3 stimulation, accompanied by elevations in NF-κB activation, cAMP levels, and the production of C-C motif chemokine ligand (CCL)2, interleukin (IL)-6, and matrix metalloproteinase (MMP) 2 cytokines. CONCLUSION: Our results suggest that FFAR2 signaling antagonized TLR2- and TLR3-induced lung cancer progression via the suppression of the cAMP-AMPK-TAK1 signaling axis for the activation of NF-κB, and its agonist might be a potential therapeutic agent for the treatment of lung cancer.

Molecular Bases of Heat Stress Responses in Vegetable Crops With Focusing on Heat Shock Factors and Heat Shock Proteins.

The effects of the climate change including an increase in the average global temperatures, and abnormal weather events such as frequent and severe heatwaves are emerging as a worldwide ecological concern due to their impacts on plant vegetation and crop productivity. In this review, the molecular processes of plants in response to heat stress-from the sensing of heat stress, the subsequent molecular cascades associated with the activation of heat shock factors and their primary targets (heat shock proteins), to the cellular responses-have been summarized with an emphasis on the classification and functions of heat shock proteins. Vegetables contain many essential vitamins, minerals, antioxidants, and fibers that provide many critical health benefits to humans. The adverse effects of heat stress on vegetable growth can be alleviated by developing vegetable crops with enhanced thermotolerance with the aid of various genetic tools. To achieve this goal, a solid understanding of the molecular and/or cellular mechanisms underlying various responses of vegetables to high temperature is imperative. Therefore, efforts to identify heat stress-responsive genes including those that code for heat shock factors and heat shock proteins, their functional roles in vegetable crops, and also their application to developing vegetables tolerant to heat stress are discussed.

Particle leakage through the exhalation valve on a face mask under flow conditions mimicking human breathing: A critical assessment.

In today's era of active personal protections against airborne respiratory disease, general interest in the multiphase flow physics underlying face masks is greater than ever. The exhalation valves, installed on some masks to mitigate the breathing resistance, have also received more attention. However, the current certification protocol of evaluating airflow leakage only when suction pressure is applied is insufficient to capture practical aspects (particle penetration or leakage). Here, we experimentally measure two-phase flow across valve-type masks under conditions mimicking actual breathing. During exhalation, a high-speed jet through the valve accelerates the transmission of particles from inside while reasonable protection from external pollutants is achieved during inhalation, which supports the warnings from various public health officials. Based on the mechanism of particle penetration found here, we hope a novel design that both achieves high-efficiency shielding and facilitates easy breathing can be developed.

Modulation of Rice Leaf Angle and Grain Size by Expressing OsBCL1 and OsBCL2 under the Control of OsBUL1 Promoter.

Leaf angle and grain size are important agronomic traits affecting rice productivity directly and/or indirectly through modulating crop architecture. OsBC1, as a typical bHLH transcription factor, is one of the components comprising a complex formed with LO9-177 and OsBUL1 contributing to modulation of rice leaf inclination and grain size. In the current study, two homologues of OsBC1, OsBCL1 and OsBCL2 were functionally characterized by expressing them under the control of OsBUL1 promoter, which is preferentially expressed in the lamina joint and the spikelet of rice. Increased leaf angle and grain length with elongated cells in the lamina joint and the grain hull were observed in transgenic rice containing much greater gibberellin A3 (GA3) levels than WT, demonstrating that both OsBCL1 and OsBCL2 are positive regulators of cell elongation at least partially through increased GA biosynthesis. Moreover, the cell elongation was likely due to cell expansion rather than cell division based on the related gene expression and, the cell elongation-promoting activities of OsBCL1 and OsBCL2 were functional in a dicot species, Arabidopsis.

Applications and Major Achievements of Genome Editing in Vegetable Crops: A Review.

The emergence of genome-editing technology has allowed manipulation of DNA sequences in genomes to precisely remove or replace specific sequences in organisms resulting in targeted mutations. In plants, genome editing is an attractive method to alter gene functions to generate improved crop varieties. Genome editing is thought to be simple to use and has a lower risk of off-target effects compared to classical mutation breeding. Furthermore, genome-editing technology tools can also be applied directly to crops that contain complex genomes and/or are not easily bred using traditional methods. Currently, highly versatile genome-editing tools for precise and predictable editing of almost any locus in the plant genome make it possible to extend the range of application, including functional genomics research and molecular crop breeding. Vegetables are essential nutrient sources for humans and provide vitamins, minerals, and fiber to diets, thereby contributing to human health. In this review, we provide an overview of the brief history of genome-editing technologies and the components of genome-editing tool boxes, and illustrate basic modes of operation in representative systems. We describe the current and potential practical application of genome editing for the development of improved nutritious vegetables and present several case studies demonstrating the potential of the technology. Finally, we highlight future directions and challenges in applying genome-editing systems to vegetable crops for research and product development.

Potential of Algae-Bacteria Synergistic Effects on Vegetable Production.

Modern agriculture has become heavily dependent on chemical fertilizers, which have caused environmental pollution and the loss of soil fertility and sustainability. Microalgae and plant growth-promoting bacteria (PGPB) have been identified as alternatives to chemical fertilizers for improving soil fertility. This is because of their biofertilizing properties, through the production of bioactive compounds (e.g., phytohormones, amino acids, and carotenoids) and their ability to inhibit plant pathogens. Although treatment based on a single species of microalgae or bacteria is commonly used in agriculture, there is growing experimental evidence suggesting that a symbiotic relationship between microalgae and bacteria synergistically affects each other's physiological and metabolomic processes. Moreover, the co-culture/combination treatment of microalgae and bacteria is considered a promising approach in biotechnology for wastewater treatment and efficient biomass production, based on the advantage of the resulting synergistic effects. However, much remains unexplored regarding the microalgal-bacterial interactions for agricultural applications. In this review, we summarize the effects of microalgae and PGPB as biofertilizing agents on vegetable cultivation. Furthermore, we present the potential of the microalgae-PGPB co-culture/combination system for the environmentally compatible production of vegetables with improved quality.

Nanochannel-driven rapid capture of sub-nanogram level biomarkers for painless preeclampsia diagnosis.

Preeclampsia (PE) is a pregnancy-specific hypertensive syndrome recognized as the leading cause of maternal and fetal morbidity and mortality worldwide. Painful blood-collection procedures or low accuracy of non-invasive approaches require faster, patient-friendly, and more sensitive diagnostic technologies. Here we report a painless, highly sensitive detection platform using nanoporous microneedles (nMNs) that enables rapid capture of biomarkers present at sub-nanogram levels. The highly porous nanostructures on the nMN surface were prepared by anodization of aluminum MN and then functionalized by immobilization of capture antibodies to detect target biomarkers based on an immunoassay method. The immuno-functionalized nMN array demonstrated rapid capture of an estrogen (E2) biomarker for PE following a 1-min incubation and exhibited a concentration-dependent change in fluorescence intensity over the E2 range of 0.5 ng mL-1 to 1000 ng mL-1 after treatment with fluorescence-detection antibodies. Remarkably, the nMN patch selectively detected sub-nanogram-levels of E2 in subcutaneous interstitial fluid from rats with increased diagnostic accuracy as compared with commercial immunoassay kits. This bio-functionalized nMN platform showed improved biosensing capability for multiple PE-related biomarkers, including hormones and proteins. Furthermore, this painless method demonstrated efficacy as a point-of-need diagnostic platform using portable smartphone-based fluorescence microscope to obtain fluorescence images of biomarker-captured nMN arrays.

Size Fractionation of Fluorescent Graphene Quantum Dots Using a Cross-Flow Membrane Filtration System.

Graphene quantum dots (GQDs) have received great attention as optical agents because of their low toxicity, stable photoluminescence (PL) in moderate pH solutions, and size-dependent optical properties. Although many synthetic routes have been proposed for producing GQD solutions, the broad size distribution in GQD solutions limits its use as an efficient optical agent. Here, we present a straightforward method for size fractionation of GQDs dispersed in water using a cross-flow filtration system and a track-etched membrane with cylindrical uniform nanopores. The GQD aqueous suspension, which primarily contained blue-emitting GQDs (B-GQDs) and green-emitting GQDs (G-GQDs), was introduced to the membrane in tangential flow and was fractionated with a constant permeate flow of about 800 L m-2 h-1 bar-1. After filtration, we observed a clear blue PL spectrum from the permeate side, which can be attributed to selective permeation of relatively small B-GQDs. The process provided a separation factor (B-GQDs/G-GQDs) of 0.74. In the cross-flow filtration system, size-dependent permeation through cylindrical nanochannels was confirmed by simulation. Our results demonstrate a feasible method facilitating size fractionation of two-dimensional nanostructures using a cross-flow membrane filtration system. Since membrane filtration is simple, cost-effective, and scalable, our approach can be applied to prepare a large amount of size-controlled GQDs required for high performance opto-electronics and bio-imaging applications.