pH-Responsive Amphiphilic Triblock Fluoropolymers as Assemble Oxygen Nanoshuttles for Enhancing PDT against Hypoxic Tumor.

Photodynamic therapy (PDT) is a cancer treatment strategy that utilizes photosensitizers to convert oxygen within tumors into reactive singlet oxygen (1O2) to lyse tumor cells. Nevertheless, pre-existing tumor hypoxia and oxygen consumption during PDT can lead to an insufficient oxygen supply, potentially reducing the photodynamic efficacy. In response to this issue, we have devised a pH-responsive amphiphilic triblock fluorinated polymer (PDP) using copper-mediated RDRP. This polymer, composed of poly(ethylene glycol) methyl ether acrylate, 2-(diethylamino)ethyl methacrylate, and (perfluorooctyl)ethyl acrylate, self-assembles in an aqueous environment. Oxygen, chlorine e6 (Ce6), and doxorubicin (DOX) can be codelivered efficiently by PDP. The incorporation of perfluorocarbon into the formulation enhances the oxygen-carrying capacity of PDP, consequently extending the lifetime of 1O2. This increased lifetime, in turn, amplifies the PDT effect and escalates the cellular cytotoxicity. Compared with PDT alone, PDP@Ce6-DOX-O2 NPs demonstrated significant inhibition of tumor growth. This study proposes a novel strategy for enhancing the efficacy of PDT.

Polymeric nanocarriers delivery systems in ischemic stroke for targeted therapeutic strategies.

Ischemic stroke is a complex, high-mortality disease with multifactorial etiology and pathogenesis. Currently, drug therapy is mainly used treat ischemic stroke in clinic, but there are still some limitations, such as limited blood-brain barrier (BBB) penetration efficiency, a narrow treatment time window and drug side effects. Recent studies have pointed out that drug delivery systems based on polymeric nanocarriers can effectively improve the insufficient treatment for ischemic stroke. They can provide neuronal protection by extending the plasma half-life of drugs, enhancing the drug's permeability to penetrate the BBB, and targeting specific structures and cells. In this review, we classified polymeric nanocarriers used for delivering ischemic stroke drugs and introduced their preparation methods. We also evaluated the feasibility and effectiveness and discussed the existing limitations and prospects of polymeric nanocarriers for ischemic stroke treatment. We hoped that this review could provide a theoretical basis for the future development of nanomedicine delivery systems for the treatment of ischemic stroke.

Integrated oral microgel system ameliorates renal fibrosis by hitchhiking co-delivery and targeted gut flora modulation.

BACKGROUND: Renal fibrosis is a progressive process associated with chronic kidney disease (CKD), contributing to impaired kidney function. Active constituents in traditional Chinese herbs, such as emodin (EMO) and asiatic acid (AA), exhibit potent anti-fibrotic properties. However, the oral administration of EMO and AA results in low bioavailability and limited kidney accumulation. Additionally, while oral probiotics have been accepted for CKD treatment through gut microbiota modulation, a significant challenge lies in ensuring their viability upon administration. Therefore, our study aims to address both renal fibrosis and gut microbiota imbalance through innovative co-delivery strategies. RESULTS: In this study, we developed yeast cell wall particles (YCWPs) encapsulating EMO and AA self-assembled nanoparticles (NPYs) and embedded them, along with Lactobacillus casei Zhang, in chitosan/sodium alginate (CS/SA) microgels. The developed microgels showed significant controlled release properties for the loaded NPYs and prolonged the retention time of Lactobacillus casei Zhang (L. casei Zhang) in the intestine. Furthermore, in vivo biodistribution showed that the microgel-carried NPYs significantly accumulated in the obstructed kidneys of rats, thereby substantially increasing the accumulation of EMO and AA in the impaired kidneys. More importantly, through hitchhiking delivery based on yeast cell wall and positive modulation of gut microbiota, our microgels with this synergistic strategy of therapeutic and modulatory interactions could regulate the TGF-ß/Smad signaling pathway and thus effectively ameliorate renal fibrosis in unilateral ureteral obstruction (UUO) rats. CONCLUSION: In conclusion, our work provides a new strategy for the treatment of renal fibrosis based on hitchhiking co-delivery of nanodrugs and probiotics to achieve synergistic effects of disease treatment and targeted gut flora modulation.

Physiologically based toxicokinetic modelling of Tri(2-chloroethyl) phosphate (TCEP) in mice accounting for multiple exposure routes.

Exposure routes are important for health risk assessment of chemical risks. The application of physiologically based toxicokinetic (PBTK) models to predict concentrations in vivo can determine the effects of harmful substances and tissue accumulation on the premise of saving experimental costs. In this study, Tri(2-chloroethyl) phosphate (TCEP), an organophosphate ester (OPE), was used as an example to study the PBTK model of mice exposed to different exposure doses by multiple routes. Different routes of exposure (gavage and intradermal injection) can cause differences in the concentration of chemicals in the organs. TCEP that enters the body through the mouth is mainly concentrated in the gastrointestinal tract and liver. However, the concentrations of chemicals that enter the skin into the mice are higher in skin, rest of body, and blood. In addition, TCEP was absorbed and accumulated very rapidly in mice, within half an hour after a single exposure. We have successfully established a mouse PBTK model of the TCEP accounting for multiple exposure Routes and obtained a series of kinetic parameters. The model includes blood, liver, kidney, stomach, intestine, skin, and rest of body compartments. Oral and dermal exposure route was considered for PBTK model. The PBTK model established in this study has a good predictive ability. More than 70% of the predicted values deviated from the measured values by less than 5-fold. In addition, we extrapolated the model to humans. A human PBTK model is built. We performed a health risk assessment for world populations based on human PBTK model. The risk of TCEP in dust is greater through mouth than through skin. The risk of TCEP in food of Chinese population is greater than dust.

Effects of different patterns of movement for correcting a deep curve of Spee with clear aligners on the anterior teeth: a finite element analysis.

OBJECTIVE: To analyse the anterior teeth effects of clear aligners on five different patterns of mandibular molar movement and to define the most effective configuration to be implemented with clear aligners through finite element analysis. METHODS: A three-dimensional mandibular model with a deep overbite in the mandible was constructed using cone beam computerized tomography (CBCT) data. The model included the mandibular dentition, mandibular periodontal ligaments, attachments, and aligners. Five models were created: (1) configuration A: second molar distalization (0.25 mm); (2) configuration B: second molar distalization (0.25 mm), first molar extrusion (0.15 mm); (3) configuration C: second molar distalization (0.25 mmm), first and second premolar extrusion(0.15 mm); (4) configuration D: second molar distalization (0.25 mm), first molar and first/second premolar extrusion(0.15 mm); and (5) configuration E: second molar distalization (0.25 mm), first molar and first/second premolar extrusion (0.15 mm), first molar and first/second premolar expansion (0.15 mm). RESULTS: In all configurations, the anterior teeth exhibited labial tipping and the mandibular central incisor of configuration E showed the highest labial tipping. Configuration E demonstrated a relatively minor impact on mandibular molars distalization compared with configuration A. Configuration A showed the highest distal displacement value, and configuration E produced the lowest displacement value. Configuration E caused the highest periodontal ligament (PDL) pressure of the central and lateral incisors. The differences in the canines between configurations C and D,were not significant, and the stress distribution differed among the five groups. CONCLUSIONS: All patterns utilizing clear aligners facilitated mandibular molar distalization. Extruding the premolars and second molar distalization at the same time had little impact on second molar distalization; When expansion and extrusion were simultaneously performed during the distalization of mandibular molars, our prime consideration was the alveolar bone on the labial side of the anterior teeth to prevent the occurrence of gingival recession, dehiscence, and fenestration. Due to the lack of consideration for periodontal tissues in this study, clinical protocols should be designed based on the periodontal status of the mandibular anterior teeth.

N6-Methyladenosine Reader YTHDF1 Promotes ARHGEF2 Translation and RhoA Signaling in Colorectal Cancer.

BACKGROUND & AIMS: N6-methyladenosine (m6A) governs the fate of RNAs through m6A readers. Colorectal cancer (CRC) exhibits aberrant m6A modifications and expression of m6A regulators. However, how m6A readers interpret oncogenic m6A methylome to promote malignant transformation remains to be illustrated. METHODS: YTH N6-methyladenosine RNA binding protein 1 (Ythdf1) knockout mouse was generated to determine the effect of Ythdf1 in CRC tumorigenesis in vivo. Multiomic analysis of RNA-sequencing, m6A methylated RNA immunoprecipitation sequencing, YTHDF1 RNA immunoprecipitation sequencing, and proteomics were performed to unravel targets of YTHDF1 in CRC. The therapeutic potential of targeting YTHDF1-m6A-Rho/Rac guanine nucleotide exchange factor 2 (ARHGEF2) was evaluated using small interfering RNA (siRNA) encapsulated by lipid nanoparticles (LNP). RESULTS: DNA copy number gain of YTHDF1 is a frequent event in CRC and contributes to its overexpression. High expression of YTHDF1 is significantly associated with metastatic gene signature in patient tumors. Ythdf1 knockout in mice dampened tumor growth in an inflammatory CRC model. YTHDF1 promotes cell growth in CRC cell lines and primary organoids and lung and liver metastasis in vivo. Integrative multiomics analysis identified RhoA activator ARHGEF2 as a key downstream target of YTHDF1. YTHDF1 binds to m6A sites of ARHGEF2 messenger RNA, resulting in enhanced translation of ARHGEF2. Ectopic expression of ARHGEF2 restored impaired RhoA signaling, cell growth, and metastatic ability both in vitro and in vivo caused by YTHDF1 loss, verifying that ARHGEF2 is a key target of YTHDF1. Finally, ARHGEF2 siRNA delivered by LNP significantly suppressed tumor growth and metastasis in vivo. CONCLUSIONS: We identify a novel oncogenic epitranscriptome axis of YTHDF1-m6A-ARHGEF2, which regulates CRC tumorigenesis and metastasis. siRNA-delivering LNP drug validated the therapeutic potential of targeting this axis in CRC.

The Application Value of Contrast-Enhanced Ultrasonography in Assessing the Efficacy of Ultrasound-Guided Lauromacrogol Injections in Cesarean Scar Pregnancies.

OBJECTIVE: To investigate the application value of contrast-enhanced ultrasonography (CEUS) in ultrasound-guided lauromacrogol injections in patients with cesarean scar pregnancies (CSP). METHODS: A total of 31 patients diagnosed with CSP, who underwent an ultrasound-guided lauromacrogol injection + curettage in our hospital between February 2019 and December 2020 and had a complete recovery confirmed by a postoperative ultrasound review and serum ß-human chorionic gonadotropin (ß-hCG) assay, were enrolled as the study subjects. According to the volume of intraoperative blood loss and the duration of postoperative vaginal bleeding, the patients were divided into two groups, with 19 in the significantly effective group (Group A) and 12 in the effective group (Group B). The recorded clinical data, including age, duration of amenorrhea, number of pregnancies, number of deliveries, time since last cesarean delivery, number of cesarean deliveries, and preoperative serum ß-hCG levels, were retrospectively analyzed. The morphological indicators in CEUS before the lauromacrogol injection, as well as immediately and 12-24 hours after the injection, were compared between the groups. RESULTS: In Group A, the post-injection CEUS showed no enhancement, single strip enhancement, and sparse punctate enhancement, while in Group B, it showed a more irregular ring and local patch enhancement. In addition, the number of cases where the CEUS showed no enhancement 12-24 hours after the injection was more than that of the immediate CEUS after the injection. In Group A, four (21.1%) cases showed a single strip-like blood flow on the immediate postoperative CEUS, four (21.1%) cases showed a sparsely dotted blood flow on the immediate postoperative CEUS, and three cases turned into no enhancement 12-24 hours after the injection. A total of four cases in Group B showed that the contrast enhancement range 12-24 hours after the injection was reduced compared with that of the immediate contrast after the injection. CONCLUSION: Contrast-enhanced ultrasonography can guide the location selection of the lauromacrogol injection in patients with CSP, and its postoperative morphological indicators can adequately predict the therapeutic effect after curettage and guide clinical management.

Transport of microplastics in the body and interaction with biological barriers, and controlling of microplastics pollution.

Microplastics (MPs) are one novel environmental pollutant sized < 5 mm that is ubiquitously present in numerous environmental media and particularly susceptible to interact with various toxic chemicals. Importantly, MPs can enter the food chain, and are bio-enriched and bio-accumulated with trophic levels, eventually endangering ecosystems and human health. However, there need to be more understanding regarding the bio-interaction of MPs with the host, particularly for biological barriers. This review aimed to summarize the latest findings regarding the main exposure routes of MPs that generated health burdens on humans. Furthermore, their interactions with biological barriers that generate adverse health effects and the underlying mechanisms were also reviewed. Additionally, we provided a comprehensive overview of recent advances regarding the removing and controlling of MPs. Finally, we discussed the future directions for MPs hazard prevention to provide helpful information for regulating decision-making and guiding safer plastics applications.

Gut microbiota combined with metabolome dissects long-term nanoplastics exposure-induced disturbed spermatogenesis.

As the concerned emerging pollutants, several lines of evidence have indicated that nanoplastics (NPs) lead to reproductive toxicity. However, the biological mechanism underlying NPs disturbed spermatogenesis remains largely unknown. Therefore, we aimed to reveal the potential mechanism of impaired spermatogenesis caused by long-term NPs exposure from the perspective of integrated metabolome and microbiome analysis. After 12 weeks of gavage of polystyrene nanoplastics (PS-NPs) and animo-modified polystyrene nanoplastics (Amino-NPs), a well-designed two-exposure stages experimental condition. We found that NPs exposure induced apparent abnormal spermatogenesis, which appeared more severe in the Amino-NPs group. Mechanistically, 14 floras associated with glucose and lipid metabolism were significantly altered, as evidenced by 16 S rRNA sequencing. Testicular metabolome revealed that the Top 50 changed metabolites were also enriched in lipid metabolism. Subsequently, the combined gut microbiome and metabolome analysis uncovered the strong correlations between Klebsiella, Blautia, Parabacteroides, and lipid metabolites (e.g., PC, LysoPC and GPCho). We speculate that the dysbiosis of gut microbiota-related disturbed lipid metabolism may be responsible for long-term NPs-induced damaged spermatogenesis, which provides new insights into NPs-induced dysregulated spermatogenesis.

The preparation, characterization, and application of porous core-shell composite particles produced with laboratory-scale spray dryer.

OBJECTIVE: To prepare porous core-shell composite particles (PCPs) in order to improve the flowability and compactibility of powder materials for direct compaction (DC), as well as the dissolution of tablets. SIGNIFICANCE: The results obtained are meaningful to boosting the development and further research of PCPs on DC. Methods: In this study, hydroxypropyl methylcellulose (HPMC E3) and polyvinylpyrrolidone (PVP K30) were selected as shell materials, the Xiao Er Xi Shi formulation powder (XEXS) was used as the core materials, ammonium bicarbonate (NH4HCO3), and sodium bicarbonate (NaHCO3) were employed as pore-forming agent. Using co-spray drying method to prepare composite particles (CPs). Then, the physical properties and comparison between different CPs were characterized comprehensively. Finally, the different CPs were directly compacted as tablets to explore the effect on the dissolution behavior of DC tablets, respectively. RESULTS: (i) The XEXS PCPs were prepared successfully by co-spray drying, and the yield of PCPs is almost 80%; (ii) The TS values of PCP-X-P-Na, PCP-X-P-NH4, PCP-X-H-Na and PCP-X-P-Na were 5.70, 7.56, 3.98, and 6.88 times higher than that of raw material (X); (iii) The disintegration time of PCPs tablets decreased 10-25% when compared with CPs tablets; (iv) The values of Carr's index (CI), Hausner ratio (HR), Caking strength (CS), and Cohesion index (CoI) of PCP-X-H-NH4 were 19.16%, 19.29%, 40.14%, and 6.39% lower than that of X, respectively. CONCLUSIONS: The PCPs prepared by co-spray drying did improve the flowability and compactibility of powder, as well as the dissolution of tablets.

Study on Improving the Performance of Traditional Medicine Extracts with High Drug Loading Based on Co-spray Drying Technology.

The purpose of this study is to develop modified particles with different structures to improve the flowability and compactibility of Liuwei Dihuang (LWDH) powder using co-spray drying technology, and to investigate the preparation mechanism of modified particles and their modified direct compaction (DC) properties. Moreover, tablets with high drug loading contents were also prepared. Particles were designed using polyvinylpyrrolidone (PVP K30) and hydroxypropyl methylcellulose (HPMC E3) as shell materials, and sodium bicarbonate (NaHCO3) and ammonium bicarbonate (NH4HCO3) as pore-forming agents. The porous particles (Ps), core-shell particles (CPs), and porous core-shell particles (PCPs) were prepared by co-spray drying technology. The key DC properties and texture properties of all the particles were measured and compared. The properties of co-spray drying liquid were also determined and analyzed. According to the results, Ps showed the least improvement in DC properties, followed by CPs, and PCPs showed a significant improvement. The modifier, because of its low surface tension, was wrapped in the outer layer to form a shell, and the pore-forming agent was thermally decomposed to produce pores, forming core-shell, porous, and porous core-shell composite structures. The smooth surface of the shell structure enhances fluidity, while the porous structure allows for greater compaction space, thereby improving DC properties during the compaction process.

p-Phenylenediamine Antioxidants in PM2.5: The Underestimated Urban Air Pollutants.

The wide use and continuous abrasion of rubber-related products appears to be leading to an incredible release of p-phenylenediamine (PPD) antioxidants in the environment. However, no related research has been conducted on the pollution characteristics and potential health risks of PM2.5-bound PPDs. We report for the first time the ubiquitous distributions of six emerging PPDs and a quinone derivative, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPDQ), in PM2.5 from urban areas of China. Atmospheric contamination levels of PM2.5-bound PPDs were found to be mostly in pg m-3 amounts between 2018 and 2019. Urban vehicle rubber tire abrasion was found to probably contribute to the PPDs in PM2.5 and accounted for their significant spatiotemporal-dependent concentration variations. Furthermore, 6PPDQ, an emerging oxidation product of 6PPD in the environment, was first quantified (pg m-3) with a total detection rate of 81% in the urban PM2.5, demonstrating its broad existence. On the basis of the determined ambient concentrations, the annual intakes of PPDs and 6PPDQ for adults were not low, indicating their possible human health risks induced by long-term exposure. This study confirms the widespread occurrence of PPDs and 6PPDQ in PM2.5, showing that the pollution of such compounds in urban air should not be underestimated.

Synthesis, Characterization of NR@SiO2/PNIPAm-co-Ppa Composite Nanogel and Study On Its Application in Photodynamic Therapy.

In the present study, a novel composite nanogel based on fluorescence resonance energy transfer (FRET) and its application for photodynamic therapy is reported. First of all, nanoparticles of silica doped with Nile Red (NR) were prepared by Stöber method, then they were decorated by γ-methacryloxypropyltrimethoxysilane (MPS) to prepare MPS decorated NR@SiO2 nanoparticles, and finally they were copolymerized with N-isopropylacrylamide (NIPAm) and Pyropheophorbide-a (Ppa) by free radical copolymerization, and composite nanogel of NR@SiO2/PNIPAm-co-Ppa was fabricated. The microstructure of the as-prepared nanogel was characterized by Fourier transform infrared spectrum (FTIR), photoluminescence (PL), UV-Visible spectrophotometer (UV-Vis), dynamic light scattering (DLS) and transmission electron microscopy (TEM). PL spectrum indicated that, under irradiation of visible light source, energy can be transferred from NR to Ppa. UV-Vis spectrum demonstrated that aggregation of Ppa is prevented efficiently and Ppa exists as "monomer" state in the composite nanogel. Under irradiation of laser, singlet oxygen (1O2) can be produced efficiently by excited nanogel. The in vitro cytotoxicity test showed that HeLa cells can be killed by the composite nanogel.

Virtual Screening and Molecular Docking to Study the Mechanism of Chinese Medicines in the Treatment of Coronavirus Infection.

BACKGROUND Heat-clearing and detoxifying herbs (HDHs) play an important role in the prevention and treatment of coronavirus infection. However, their mechanism of action needs further study. This study aimed to explore the anti-coronavirus basis and mechanism of HDHs. MATERIAL AND METHODS Database mining was performed on 7 HDHs. Core ingredients and targets were screened according to ADME rules combined with Neighborhood, Co-occurrence, Co-expression, and other algorithms. GO enrichment and KEGG pathway analyses were performed using the R language. Finally, high-throughput molecular docking was used for verification. RESULTS HDHs mainly acts on NOS3, EGFR, IL-6, MAPK8, PTGS2, MAPK14, NFKB1, and CASP3 through quercetin, luteolin, wogonin, indirubin alkaloids, ß-sitosterol, and isolariciresinol. These targets are mainly involved in the regulation of biological processes such as inflammation, activation of MAPK activity, and positive regulation of NF-kappaB transcription factor activity. Pathway analysis further revealed that the pathways regulated by these targets mainly include: signaling pathways related to viral and bacterial infections such as tuberculosis, influenza A, Ras signaling pathways; inflammation-related pathways such as the TLR, TNF, MAPK, and HIF-1 signaling pathways; and immune-related pathways such as NOD receptor signaling pathways. These pathways play a synergistic role in inhibiting lung inflammation and regulating immunity and antiviral activity. CONCLUSIONS HDHs play a role in the treatment of coronavirus infection by regulating the body's immunity, fighting inflammation, and antiviral activities, suggesting a molecular basis and new strategies for the treatment of COVID-19 and a foundation for the screening of new antiviral drugs.

Symptom management to alleviate thirst and dry mouth in critically ill patients: A randomised controlled trial.

BACKGROUND: Critically ill patients often experience coexisting symptoms. Thirst, in particular, appears to be an important symptom, having the highest prevalence, intensity, and induction of distress, and is significantly correlated with other symptoms. However, thirst and dry mouth are not usually assessed or treated. OBJECTIVES: The aim of the study was to demonstrate the effectiveness of an intervention bundle to relieve thirst and dry mouth. METHODS: The present study was a randomised controlled trial in which critically ill patients were allocated to an experimental or control group. The intervention bundles, including vitamin C sprays, peppermint water mouthwash, and a lip moisturiser, were provided to the experimental group for 3 days, whereas patients in the control group were exposed to the placebo interventions, including saline sprays, 40 °C water mouthwash, and wetting the lips with water. RESULTS: A total of 61 patients were recruited to the study; 65.6% (n = 41) were men, and the average age was 64.2 ± 16.8 years. The average decrease in thirst intensity and oral mucosa situation scores after the interventions was larger in the experimental group patients relative to controls (1.27 and 0.36 vs. 0.19 and 0.1 points, respectively; p < 0.05). Being male, scoring highly on the Acute Physiology and Chronic Health Evaluation II scale, not receiving diuretics, and having higher serum sodium levels were potential predictors of thirst and oral dryness. CONCLUSIONS: The interventional bundle used in this study was shown to be a promising approach that can relieve thirst intensity and dry mouth, which are pervasively distressful to critically ill patients. CLINICAL TRIAL REGISTRATION NUMBERS: The study was registered on the www.Chictr.org.cn under the identification number ChiCTR1900022873.

Tumor-targeted drug delivery and sensitization by MMP2-responsive polymeric micelles.

Low tumor specificity and multidrug resistance (MDR) remain challenging for many anticancer drugs. In this study, the micelles assembled by a matrix metalloproteinase 2 (MMP2)-sensitive self-assembling efflux inhibitor (PEG2k-pp-PE) were developed and evaluated in various cancer models. In vitro, the PEG2k-pp-PE micelles enhanced the cellular uptake and tissue penetration and sensitized the cancers to drug treatments in MDR cancer cells and their three-dimensional multicellular spheroids. Their efflux inhibitory capability was comparable to those of the well-known small-molecule P-glycoprotein (P-gp) inhibitor and polymeric P-gp inhibitor. In vivo, the PEG2k-pp-PE micelles could specifically and effectively deliver the loaded cargoes to the tumor, as evidenced by the enhanced drug accumulation and prolonged drug retention in the tumor tissue, resulting in the improved anticancer activity. Our results suggest that the PEG2k-pp-PE micelles may have great potential to be a simple but multifunctional nanocarrier for concurrent tumor-targeted drug delivery and sensitization of resistant cancers.

Mucor indicus and Rhizopus oryzae co-culture to improve the flavor of Chinese turbid rice wine.

BACKGROUND: One of the most important species used to ferment Chinese turbid rice wine (CTRW) at an industrial-scale level is Rhizopus oryzae, although the flavor of CTRW fermented by pure R. oryzae is inferior to that of traditional CTRW. RESULTS: Mucor indicus was used as a cooperative species to improve the flavor of CTRW presented by R. oryzae. The flavor compounds in different fermentation stages were determined by headspace solid-phase microextraction-gas chromatography-mass spectrometry and high-performance liquid chromatography. It was noted that the M. indicus and R. oryzae co-culture changed the profiles of flavor compounds in CTRW, including esters, higher alcohols, amino acids and organic acids, and also significantly enhanced the concentration of sweet amino acids, fruity and floral esters, and higher alcohols. Sensory evaluation demonstrated that the CTRW fermented by M. indicus and R. oryzae had a more intense aroma, harmonious taste, continuation and full body mouth-feel because of more abundant flavor compounds. CONCLUSION: Mucor indicus is a promising species for co-culture with R. oryzae to improve the flavor of CTRW. © 2019 Society of Chemical Industry.

Mouth and Voice: A Relationship between Visual and Auditory Preference in the Human Superior Temporal Sulcus.

Cortex in and around the human posterior superior temporal sulcus (pSTS) is known to be critical for speech perception. The pSTS responds to both the visual modality (especially biological motion) and the auditory modality (especially human voices). Using fMRI in single subjects with no spatial smoothing, we show that visual and auditory selectivity are linked. Regions of the pSTS were identified that preferred visually presented moving mouths (presented in isolation or as part of a whole face) or moving eyes. Mouth-preferring regions responded strongly to voices and showed a significant preference for vocal compared with nonvocal sounds. In contrast, eye-preferring regions did not respond to either vocal or nonvocal sounds. The converse was also true: regions of the pSTS that showed a significant response to speech or preferred vocal to nonvocal sounds responded more strongly to visually presented mouths than eyes. These findings can be explained by environmental statistics. In natural environments, humans see visual mouth movements at the same time as they hear voices, while there is no auditory accompaniment to visual eye movements. The strength of a voxel's preference for visual mouth movements was strongly correlated with the magnitude of its auditory speech response and its preference for vocal sounds, suggesting that visual and auditory speech features are coded together in small populations of neurons within the pSTS.SIGNIFICANCE STATEMENT Humans interacting face to face make use of auditory cues from the talker's voice and visual cues from the talker's mouth to understand speech. The human posterior superior temporal sulcus (pSTS), a brain region known to be important for speech perception, is complex, with some regions responding to specific visual stimuli and others to specific auditory stimuli. Using BOLD fMRI, we show that the natural statistics of human speech, in which voices co-occur with mouth movements, are reflected in the neural architecture of the pSTS. Different pSTS regions prefer visually presented faces containing either a moving mouth or moving eyes, but only mouth-preferring regions respond strongly to voices.

Oolong tea: A critical review of processing methods, chemical composition, health effects, and risk.

Oolong tea (OT) is a traditional Chinese tea (Camellia sinensis) and is especially popular in south China. This review is to comprehensively summarize the miscellaneous research that has been done towards to the processing, phytochemistry, health benefit, and risk of OT. These literatures were carried out not only from different electronic databases but also from text books written in English, Japanese, and Chinese, including those traditional records tracing back to the Tang Dynasty (A.D. 618-907). The full process OT producing is depicted below in this review. The phytochemistry of OT has been comprehensively investigated. More than 100 chemical compositions have been isolated and identified. In health benefit, OT performs outstandingly in reducing obesity and controlling diabetes explained by modern pharmacological studies. (-)-Epigallocatechin-3-gallate (6) in OT prevention of cancerous cells developing. OT can also improve and reduce on heart and vascular disease, protect teeth and bone, function as anti-oxidative and antibacterial agents. This review also mentioned the risk, summarized briefly on various forms of toxicity and harmful associated with OT. In short, this review can provided a natural product library of OT, gave inspirations for further new garden systems, designed idea on quality, bioactivity-oriented screening. In addition, it is suggested more scientists and education is necessary to guarantee the stability and safety of drinking OT.

[Clinicopathological Analysis of Autoimmune Hepatitis with Sjögren's Syndrome].

OBJECTIVE: To explore the biochemical-immune and pathological characteristics of autoimmune hepatitis (AIH) with Sjögren's syndrome (SS) . METHODS: A total of 76 cases of AIH patients were included from January 2009 to April 2017. Among them,there were 40 cases of AIH with SS and 36 cases without SS. The liver function,immunological index,histological features,length of first diagnosis and treatment costs were compared between the two groups. RESULTS: For AIH+SS group and AIH group,the proportion of women were 97.5% and 77.8%,the proportion of the first diagnosis age less than 60 years were 70% and 47.2%,the median course of disease were 30 months and 9 months,all the difference were statistically significant (P<0.05). The chief complaints in AIH+SS group and AIH group were as follows: cutaneous or scleracterus (52.5% vs. 38.9%),abnormal transaminase (17.5% vs. 44.4%),dryness of mouth and eye (15.0% vs. 2.8%),all the difference were statistically significant (P<0.05). There were no statistically significant difference in hospitalization expenses,and length of stay between the two groups (P>0.05). The median level of total bilirubin (TBIL),direct bilirubin (DBIL) and immunoglobulin (Ig) M of AIH +SS group were higher than those of AIH group,the mean level of albumin (ALB) and complement 3 (C3) of AIH +SS group were lower than those of AIH group,and the positive rate of anti-mitochondrial antibody-M2 (AMA-M2) ,anti-Ro antibody A (SSA),anti-La antibody (SSB) and anti-soluble liver antigen antibody (SLA) of AIH+SS group were higher than those of AIH group (P<0.05). There were no statistically significant difference in histological changes of hepatocytes and bile duct injury rate (P>0.05). CONCLUSION: AIH patients in young and middle-aged women need to be vigilant with SS with main manifestation of skin sclera and high specific autoantibodies positive.