Multilayer track-etched membrane-based electroosmotic pump for drug delivery.

Herein, we report an electroosmotic pump (EOP) based on a multilayer track-etched polycarbonate (PC) membrane. A remarkable increase of maximum backpressure (198.2-2400 mmH2 O) of a fundamental pump unit was obtained at 0.8 mA, when the number of PC membranes was increased from 1 to 10. Meanwhile, the corresponding flow rate was increased from 80.3 to 111.7 µL/min. Furthermore, multiple pump units were assembled in series to obtain a multistage EOP. For a three-stage EOP (EOP-3), the operating voltage and power can be decreased significantly by 52%-72% under different driving currents, with a minimum power of 26.7 µW. Thus, EOP-3 can run stably over 35 h at a pulse current of 0.1 mA without the generation of gas bubbles. The pump was further integrated into a miniature device, which was successfully used to decrease the blood glucose level of diabetic rats by subcutaneous delivery of fast-acting insulin. This work brings a facile and efficient strategy to enhance the backpressure and lower the operating voltage and power of EOPs, which may find promising applications in drug delivery.

A Novel Quercetin Encapsulated Glucose Modified Liposome and Its Brain-Target Antioxidative Neuroprotection Effects.

Neurodegenerative diseases (NDDs) are mainly induced by oxidative stress which produces excessive reactive oxygen species (ROS). Quercetin (QU) is a potent antioxidant with some effects on NDDs. This study prepared and characterized a novel glucose-modified QU liposome (QU-Glu-Lip), aiming not only to overcome QU's poor water solubility and bioavailability but also to deliver more QU to brain tissue to enhance its neuroprotective effect. QU-Glu-Lip possessed encapsulation efficiency (EE) of 89.9%, homogenous particle sizes (116-124 nm), small PDI value (<0.3), zeta value -1.363 ± 0.437 mV, proper pH and salt stability, and proper cytotoxicity. The glucose-modified liposome penetrated the blood-brain barrier (BBB) mediated via the glucose transporter 1 (GLUT1) and was taken by neuronal cells more efficiently than liposome without glucose, according to bEnd.3 and PC12 cell tests. QU-Glu-Lip attenuated H2O2-induced oxidative damage to PC12 with higher cell viability (88.42%) and lower intracellular ROS compared to that of QU. QU-Glu-Lip had higher brain target ability and delivered more QU to neuronal cells, effectively exerting the antioxidative neuroprotection effect. There is potential for the QU-Glu-Lip application for more effective treatment of NDDs.

Force-Triggered Atropisomerization of a Parallel Diarylethene to Its Antiparallel Diastereomers.

This paper describes a mechanical approach to inducing the atropisomerization of a parallel diarylethene into its antiparallel diastereomers exhibiting distinct chemical reactivity. A congested parallel diarylethene mechanophore in the (Ra,Sa)-configuration with mirror symmetry is atropisomerized to its antiparallel diastereomers with C2 symmetry under ultrasound-induced force field. The resulting stereochemistry-converted material gains symmetry-allowed reactivity toward conrotatory photocyclization.

COF-Coated Microelectrode for Space-Confined Electrochemical Sensing of Dopamine in Parkinson's Disease Model Mouse Brain.

Parkinson's disease (PD) is a progressive neurodegenerative disorder causing the loss of dopaminergic neurons in the substantia nigra and the drastic depletion of dopamine (DA) in the striatum; thus, DA can act as a marker for PD diagnosis and therapeutic evaluation. However, detecting DA in the brain is not easy because of its low concentration and difficulty in sampling. In this work, we report the fabrication of a covalent organic framework (COF)-modified carbon fiber microelectrode (cCFE) that enables the real-time detection of DA in the mouse brain thanks to the outstanding antibiofouling and antichemical fouling ability, excellent analytical selectivity, and sensitivity offered by the COF modification. In particular, the COF can inhibit the polymerization of DA on the electrode (namely, chemical fouling) by spatially confining the molecular conformation and electrochemical oxidation of DA. The cCFE can stably and continuously work in the mouse brain to detect DA and monitor the variation of its concentration. Furthermore, it was combined with levodopa administration to devise a closed-loop feedback mode for PD diagnosis and therapy, in which the cCFE real-time monitors the concentration of DA in the PD model mouse brain to instruct the dose and injection time of levodopa, allowing a customized medication to improve therapeutic efficacy and meanwhile avoid adverse side effects. This work demonstrates the fascinating properties of a COF in fabricating electrochemical sensors for in vivo bioanalysis. We believe that the COF with structural tunability and diversity will offer enormous promise for selective detection of neurotransmitters in the brain.

Forty years of development of salpingitis animal modeling.

This review summarizes and examines research in the area of salpingitis animal modeling in the last 40 years, focusing primarily on Chlamydia trachomatis animal models, which are the most numerous in the literature. Early animal models are examined, followed by a discussion of study parameters and their impact on modeling success, subsequent considerations of fertility measures in modeling, explorations of treatment options, and finally exploring recent directions with a brief discussion of models using other bacterial pathogens.

Tailored diffusion limiting membrane for microneedle glucose sensors with wide linear range.

Continuous glucose monitoring is very important to daily blood glucose control in diabetic patients, but its accuracy is limited by the narrow linear range of the response of biosensor to the glucose concentration because of the oxygen starvation in tissue and the limited maximum conversion rate of glucose oxidase. In this work, a biocompatible diffusion limiting membrane based on two medical-grade polyurethanes is developed via blending modification to restrict the diffusion flux of glucose to match the oxygen concentration and the maximum conversion rate. The expansiveness of the linear range for the nanomaterials-modified electrode in the glucose biosensor can be achieved through the regulation of two polyurethanes, the solvent, and the thickness of the membrane. In addition, the mass transport of hydrogen peroxide and interfering substances is also limited of the membrane. The in vitro experiments demonstrated that the membrane-modified microneedle biosensor exhibited a rapid response to the concentration variation of glucose, a wide linear range that is sufficient to cover the blood concentration of healthy and diabetic people, the ability to resist the oxygen concentration fluctuation and interfering substances, good reproducibility and long-term stability. The custom wearable electrochemical system, possessing these characteristics, has been proven to accurately monitor the blood concentration in a living rat in real time. This demonstrates a significant potential for application in both daily and clinical blood glucose monitoring.

Pharmacological Mechanism of Chinese Medicine in Systemic Lupus Erythematosus: A Narrative Review.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder affecting multiple systems, characterized by the development of harmful autoantibodies and immune complexes that lead to damage in organs and tissues. Chinese medicine (CM) plays a role in mitigating complications, enhancing treatment effectiveness, and reducing toxicity of concurrent medications, and ensuring a safe pregnancy. However, CM mainly solves the disease comprehensively through multi-target and multi-channel regulation process, therefore, its treatment mechanism is often complicated, involving many molecular links. This review introduces the research progress of pathogenesis of SLE from the aspects of genetics, epigenetics, innate immunity and acquired immunity, and then discusses the molecular mechanism and target of single Chinese herbal medicine and prescription that are commonly used and effective in clinic to treat SLE.

α-Pyrone mediates quorum sensing through the conservon system in Nocardiopsis sp.

Actinobacteria produce a plethora of bioactive secondary metabolites that are often regulated by quorum-sensing signaling molecules via specific binding to their cognate TetR-type receptors. Here, we identified monocyclic α-pyrone as a new class of actinobacterial signaling molecules influencing quorum sensing process in Nocardiopsis sp. LDBS0036, primarily evidenced by a significant reduction in the production of phenazines in the pyrone-null mutant compared to the wild-type strain. Exogenous addition of the α-pyrone can partially restore the expression of some pathways to the wild strain level. Moreover, a unique multicomponent system referred to as a conservon, which is widespread in actinobacteria and generally contains four or five functionally conserved proteins, may play an important role in detecting and transmitting α-pyrone signals in LDBS0036. We found the biosynthetic gene clusters of α-pyrone and their associated conservon genes are highly conserved in Nocardiopsis, indicating the widespread prevalence and significant function of this regulate mechanism within Nocardiopsis genus. Furthermore, homologous α-pyrones from different actinobacterial species were also found to mediate interspecies communication. Our results thus provide insights into a novel quorum-sensing signaling system and imply that various modes of bacterial communication remain undiscovered.

A Wearable Integrated Microneedle Electrode Patch for Exercise Management in Diabetes.

Exercise is one of the preferred management strategies for diabetic patients, but the exercise mode including type, intensity, and duration time is quite different for each patient because of individual differences. Inadequate exercise has no effect on the blood glucose control, while overexercise may cause serious side effects, such as hypoglycemia and loss of blood glucose control. In this work, we report a closed-loop feedback mode for exercise management in diabetes. A minimally invasive, biocompatible microneedle electrode patch was fabricated and used for continuously monitoring the glucose in the interstitial fluid. Further, in conjunction with using a wireless electrochemical device, the glucose signals can be analyzed to output the potency of exercise and give advice on exercise management. A custom exercise given by this closed-loop feedback mode can reduce the used dose of insulin and avoid side effect during and after exercise. We believe that this work can provide a novel comprehensive guidance for diabetic patients.

The Treatment of Tubal Inflammatory Infertility using Yinjia Tablets through EGFR/MEK/ERK Signaling Pathway based on Network Pharmacology.

Background: Salpingitis obstructive infertility (SOI) refers to infertility caused by abnormal conditions such as tubal adhesion and blockage caused by acute and chronic salpingitis. SOI has a serious impact on women's physical and mental health and family harmony, and it is a clinical problem that needs to be solved urgently.

Objective: The purpose of the present study was to explore the potential pharmacological mechanisms of the Yinjia tablets (Yin Jia Pian, YJP) on tubal inflammation.

Methods: Networks of YJP-associated targets and tubal inflammation-related genes were constructed through the STRING database. Potential targets and pathway enrichment analysis related to the therapeutic efficacy of YJP were identified using Cytoscape and Database for Annotation, Visualization, and Integrated Discovery (metascape). E. coli was used to establish a rat model of tubal inflammation and to validate the predictions of network pharmacology and the therapeutic efficacy of YJP. H&E staining was used to observe the pathological changes in fallopian tubes. TEM observation of the ultrastructure of the fallopian tubes. ELISA was used to detect the changes of IL-6 and TNF-α in fallopian tubes. Immunohistochemistry was used to detect the expression of ESR1. The changes of Bcl-2, ERK1/2, p-ERK1/2, MEK, p-MEK, EGFR, and p-EGFR were detected by western blot.

Results: Through database analysis, it was found that YJP shared 105 identical targets with the disease. Network pharmacology analysis showed that IL-6, TNF, and EGFR belong to the top 5 core proteins associated with salpingitis, and EGFR/MEK/ERK may be the main pathway involved. The E. coli-induced disease rat model of fallopian tube tissue showed damage, mitochondrial disruption, and increased levels of the inflammatory factors IL-6 and TNF-α. Tubal inflammatory infertility rats have increased expression of Bcl-2, p-ERK1/2, p-MEK, and p-EGFR, and decreased expression of ESR1. In vivo, experiments showed that YJP improved damage of tissue, inhibited shedding of tubal cilia, and suppressed the inflammatory response of the body. Furthermore, YJP inhibited EGFR/MEK/ERK signaling, inhibited the apoptotic protein Bcl-2, and upregulated ESR1.

Conclusion: This study revealed that YJP Reducing tubal inflammation and promoting tissue repair may be associated with inhibition of the EGFR/MEK/ERK signaling pathway.

Phytochemical composition of Tibetan tea fermented by Eurotium cristatum and its effects on type 1 diabetes mice and gut microbiota.

"Golden-flower" Tibetan tea (GTT) is an innovative dark tea fermented via fungus Eurotium cristatum. To study GTT effects on alleviating the symptoms of type 1 diabetes mellitus (T1DM), GTT's extract (GTTE) was prepared. GTTE chemical compositions were analyzed via HPLC, pyrolysis-gas chromatography-mass (Py-GC-MS) spectrometry analysis, and chemistry analyses. GTTE effects on T1DM were explored on T1DM mice model induced by streptozotocin (STZ). GTTE was composed mainly of tea pigment theabrownin (TB) (49.18%), with high percentages of polysaccharide (16.93%), protein (10.15%), polyphenols (13.90%), amino acids (5.89%), caffeine (1.83%), and flavonoids (0.67%). Py-GC-MS results exhibited that GTTE constituted of phenols, lipids, sugars, and proteins. GTTE attenuated T1DM conditions of mice, relieved their liver and pancreatic injury, restored damaged islet cells, decreased oxidative stress by increasing superoxide dismutase (SOD) and catalase (CAT) levels, modulated cytokine expression leading to the decreasing pro-inflammatory cytokines TNF-α and IL-6, increased anti-inflammatory cytokines IL-4 to improve inflammatory responses, and optimized gut microbiota composition and structure based on high-throughput 16S rDNA sequencing, suggesting multi-channel anti-diabetes mechanisms.

Comprehensive Analysis of Phenolic Constituents, Biological Activities, and Derived Aroma Differences of Penthorum chinense Pursh Leaves after Processing into Green and Black Tea.

Penthorum chinense Pursh (Penthoraceae) is a traditional herb used in Miao medical systems that is also processed into foods (e.g., tea products) in China. Different processing methods significantly affect the volatile compounds, phenolic constituents, and biological activities. This study aimed to produce P. chinense green tea leaves (GTL), black tea leaves (BTL), and untreated leaves (UL) to investigate differences in their flavor substances, functional components, antioxidant activity, alcohol dehydrogenase (ADH) activity, and acetaldehyde dehydrogenase (ALDH) activity. The results showed that 63, 56, and 56 volatile compounds were detected in UL, GTL, and BTL, respectively, of which 43 volatile compounds were identified as differential metabolites among them. The total phenolic content (97.13-179.34 mg GAE/g DW), flavonoid content (40.07-71.93 mg RE/g DW), and proanthocyanidin content (54.13-65.91 mg CE/g DW) exhibited similar trends, decreasing in the order of UL > BTL > GTL. Fourteen phenolic compounds were determined, of which gallic acid, (-)-epicatechin, and pinocembrin 7-O-glucoside showed a sharp decrease in content from UL to BTL, while the content of pinocembrin 7-O-(3″-O-galloy-4″, 6″-hexahydroxydiphenoyl)-glucoside and pinocembrin significantly increased. GTL showed better DPPH/ABTS·+ scavenging ability and ferric-reducing ability than UL. The ADH and ALDH activities decreased in the order of GTL > UL > BTL. Therefore, tea products made with P. chinense leaves contained an abundance of functional compounds and showed satisfactory antioxidant and hepatoprotective activities, which are recommended for daily consumption.

Circular olefin copolymers made de novo from ethylene and α-olefins.

Ethylene/α-olefin copolymers are produced in huge scale and widely used, but their after-use disposal has caused plastic pollution problems. Their chemical inertness made chemical re/upcycling difficult. Ideally, PE materials should be made de novo to have a circular closed-loop lifecycle. However, synthesis of circular ethylene/α-olefin copolymers, including high-volume, linear low-density PE as well as high-value olefin elastomers and block copolymers, presents a particular challenge due to difficulties in introducing branches while simultaneously installing chemical recyclability and directly using industrial ethylene and α-olefin feedstocks. Here we show that coupling of industrial coordination copolymerization of ethylene and α-olefins with a designed functionalized chain-transfer agent, followed by modular assembly of the resulting AB telechelic polyolefin building blocks by polycondensation, affords a series of ester-linked PE-based copolymers. These new materials not only retain thermomechanical properties of PE-based materials but also exhibit full chemical circularity via simple transesterification and markedly enhanced adhesion to polar surfaces.

In Vivo Electrochemical Measurement of Glucose Variation in the Brain of Early Diabetic Mice.

Diabetes is a chronic disease caused by a decrease in insulin level or insulin resistance. Diabetes also has detrimental effects on the brain, which can lead to the injury of the blood-brain barrier and influence the glucose transport. In this study, we use in vivo electrochemical measurement to explore the glucose variation in the brain of early diabetic mice. The glucose level in mice brain is measured using a carbon fiber microelectrode modified with the osmium-derivatized polymer and glucose oxidase. The electrode shows an excellent electrochemical performance, antibiofouling ability, and high stability, which can work stably in the mice brain for 2 h. By monitoring the glucose level in the brain of normal and diabetic mice after injection of concentrated glucose solution into the abdominal cavity, it is found that the variation of cerebral glucose decreases by ∼2 fold for diabetic mice. It is proposed that diabetes can downregulate the activity of glucose transporter in the brain and finally inhibit the brain glucose uptake.

Chemresistor Smart Sensors from Silk Fibroin-Graphene Composites for Touch-free Wearables.

With the rapid development of wearable electronics, low-cost, multifunctional, ultrasensitive touch-free wearables for human-machine interaction and human/plant healthcare management have attracted great attention. The experience of fighting the COVID-19 epidemic has also confirmed the great significance of contactless sensation. Herein, a wearable smart-sensing platform using silk fibroin-reduced graphene oxide (SF-rGO) as bifunctional sensing active layers has been fabricated and integrated with a noncontact moisture/thermo sensor and Joule heater. As a result, the as-prepared smart sensor operated at 0.1 V exhibits good stability and sensitivity (sensor response of 60 for 97% RH) under a wide linear range of 6-97% RH, fast response/recover speed (real test: 21.51 s/85.62 s) toward touch-free humidity/temperature sensing for wearables, and thermal readings that can be accurately corrected by Joule heater. Impressively, it can achieve breath monitoring, mental state prediction, or elevator switching by identifying fingertip humidity variation. Prospectively, this all-in-one wearable smart sensor would set an example for improving sensing performance from structure-function relationship points of view and building a noncontact sensing system for daily life.

Evaluation of the Antioxidant Potential of Citrus medica from Different Geographical Regions and Characterization of Phenolic Constituents by LC-MS.

The varying antioxidant potential of Citrus medica associated with different geographical regions makes the evaluation of C. medica for natural antioxidants essential. This work aimed to compare the antioxidant potential of the phenolic constituents from different geographical regions. The chemical compositions were characterized by ultra-high-performance liquid chromatography (UPLC) coupled with mass spectrometry (MS). A total of 67 compounds including 29 coumarin derivatives and 38 flavonoids were tentatively identified by UPLC-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). To evaluate the quality of C. medica from seven different geographical regions, water and 80% methanol fractions were subjected to quantitative analysis. Antioxidant potentials were determined by 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), iron chelation, and reduction methods. The samples collected from Sichuan province showed the highest content of total phenolic compounds. Combined with antioxidant results, the sample from Sichuan province presented good antioxidant activity. This study also showed that total phenolic compounds significantly contributed to the antioxidant activities (2,2-azinobis(3-ethyl-benzothiazoline-6-sulphonic acid) and radical scavenging activity) of C. medica samples (p < 0.01). These results provided chemical information and potential antioxidant value for further research, providing ideal evidence for the quality evaluation and exploitation of the source.

An integrated microfluidic electrochemiluminescence device for point-of-care testing of acute myocardial infarction.

Heart-type fatty acid binding protein (H-FABP) is an early biomarker for acute myocardial infarction. The concentration of H-FABP in circulation sharply increases during myocardial injury. Therefore, fast and accurate detection of H-FABP is of vital significance. In this study, we developed an electrochemiluminescence device integrated with microfluidic chip (designed as m-ECL device) for on-site detection of H-FABP. The m-ECL device is consisted of a microfluidic chip that enable easy liquid handling as well as an integrated electronic system for voltage supply and photon detection. A sandwich-type ECL immunoassay strategy was employed for H-FABP detection by using Ru (bpy)32+ loaded mesoporous silica nanoparticles as ECL probes. This device can directly detect H-FABP in human serum without any pre-treatment, with a wide linear range of 1-100 ng/mL and a low limit of detection of 0.72 ng/mL. The clinical usability of this device was evaluated using clinical serum samples from patients. The results obtained from m-ECL device are well matched with those obtained from ELISA assays. We believe this m-ECL device has extensive application prospects for point-of-care testing of acute myocardial infarction.

Does Mobile Internet Use Affect the Loneliness of Older Chinese Adults? An Instrumental Variable Quantile Analysis.

Based on the 2018 China Family Panel Studies (CFPS) data, we empirically analyze the effect, heterogeneity, quantile differences and influencing mechanisms of mobile Internet use on loneliness in the elderly. The study found that the loneliness of the elderly who used mobile Internet was 33.1% lower than that of the elderly who did not use the mobile Internet The study also passed the robustness test. There is heterogeneity in the effect of mobile Internet use on loneliness among the elderly of different ages, educational levels and marital status. Among them, the use of mobile Internet has a significant alleviating effect on the loneliness of the 60-70-year-old elderly, those of junior high school education level and below, and the elderly with a partner. The quantile regression analysis showed that the elderly group with a high level of loneliness benefited more from the use of mobile Internet. Mediation analysis further showed that mobile Internet use can improve parent-child relationship, increase offline interactions with children, and reduce children's tangible support, which we interpret as a potential mechanism for mobile Internet use to alleviate loneliness in the elderly.

Complete genome sequence of piezotolerant Stutzerimonas kunmingensis 7850S isolated from the sediment of the Mariana Trench.

Stutzerimonas kunmingensis 7850S is a piezotolerant bacterium isolated from the sediment of the Mariana trench. Here, we described the complete genome of strain 7850S, which contains a single circular chromosome of 4,775,870 base pairs with 62.66% G + C content, and harbors 4494 protein-coding genes, 65 transfer RNA genes, and 12 ribosomal RNA genes. The experimental results showed that strain 7850S could grow under hydrostatic pressure of 0.1-70 MPa. Genomic analyses led to identifications of numbers of high hydrostatic pressure-associated genes, such as the ones associated with unsaturated fatty acids, betaine, and ectoine. A complete set of denitrification genes and some heavy metal detoxification genes were also found in this strain. The presence of these genes suggests metabolic characteristics for adaption to hadal environments and provides insights to further understand adaption strategies and ecological roles of Stutzerimonas in hadal environments.

Comprehensive Profiling of Macamides and Fatty Acid Derivatives in Maca with Different Postharvest Drying Processes Using UPLC-QTOF-MS.

Macamides are characteristically found in maca (Lepidium meyenii Walper). Fatty acid derivatives are also an important type of constituent in maca, since they not only relate to the biosynthesis of macamides in the postharvest process but also possess some bioactivities. To study their comprehensive profiles in maca tubers processed via the air-drying method, ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) analyses were performed to identify macamide and fatty acid molecules. Their contents in maca tubers that were processed via air drying and freeze drying, respectively, were further quantified using high-performance liquid chromatography (HPLC) analyses comparing with eight macamide and three fatty acid reference standards. A total of 19 macamides (including four novel ones) and 16 fatty acid derivatives (two found in maca for the first time) were identified. Quantification analyses results showed the eight macamides with contents ranging from 31.39 to 1163.19 µg/g (on dry tuber), and fatty acids from 18.71 to 181.99 µg/g in the air-dried maca, but there were only three macamides and one fatty acid detected with very low contents (3.97-34.36 µg/g) in the freeze-dried maca. The results demonstrated that the air-drying method can increase the accumulations of macamides and fatty acids in the metabolism of maca in the postharvest process. The biosynthesis of two types of macamides, i.e., N-benzyl-oxo-octadecadienamides and N-benzyl-oxo-octadecatrienamides, was further elucidated in detail. These results provide more valuable insights into the phytochemicals of maca, which is helpful to explain its health benefits.