Altered synaptic currents, mitophagy, mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention.

Emerging research suggests a potential association of progression of Alzheimer's disease (AD) with alterations in synaptic currents and mitochondrial dynamics. However, the specific associations between these pathological changes remain unclear. In this study, we utilized Aß42-induced AD rats and primary neural cells as in vivo and in vitro models. The investigations included behavioural tests, brain magnetic resonance imaging (MRI), liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, Nissl staining, thioflavin-S staining, enzyme-linked immunosorbent assay, Golgi-Cox staining, transmission electron microscopy (TEM), immunofluorescence staining, proteomics, adenosine triphosphate (ATP) detection, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) assessment, mitochondrial morphology analysis, electrophysiological studies, Western blotting, and molecular docking. The results revealed changes in synaptic currents, mitophagy, and mitochondrial dynamics in the AD models. Remarkably, intervention with Dengzhan Shengmai (DZSM) capsules emerged as a pivotal element in this investigation. Aß42-induced synaptic dysfunction was significantly mitigated by DZSM intervention, which notably amplified the frequency and amplitude of synaptic transmission. The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions, including the hippocampal CA3, primary cingular cortex, prelimbic system, and dysgranular insular cortex. DZSM intervention led to increased IDE levels, augmented long-term potential (LTP) amplitude, and enhanced dendritic spine density and length. Moreover, DZSM intervention led to favourable changes in mitochondrial parameters, including ROS expression, MMP and ATP contents, and mitochondrial morphology. In conclusion, our findings delved into the realm of altered synaptic currents, mitophagy, and mitochondrial dynamics in AD, concurrently highlighting the therapeutic potential of DZSM intervention.

Characterization of a novel VenusX orthogonal dual-layer multileaf collimator.

PURPOSE: To investigate and characterize the performance of a novel orthogonal dual-layer alpha multileaf collimator (αMLC) mounted on the LinaTech VenusX linac. METHODS: We evaluated leaf positioning accuracy and reproducibility using an electronic portal imaging device through the picket fence test. The average, interleaf, intraleaf, and leaf tip transmissions of the single and dual layers were measured using an ionization chamber. Square and rhombus fields were used to evaluate the leaf penumbra of αMLC. To investigate the advantages of the orthogonal dual-layer multileaf collimator (MLC) in field shaping, right triangular and circular pattern fields were formed using both the dual layers and single layers of the αMLC. RESULTS: The average maximum positioning deviations of the upper and lower αMLC over 1 year were 0.76 ± 0.09 mm and 0.62 ± 0.07 mm, respectively. The average transmissions were 1.87%, 1.83%, and 0.03% for the upper-, lower- and dual-layer αMLC, respectively. The maximum interleaf transmissions of the lower- and dual-layer were 2.43% and 0.17%, respectively. The leaf tip transmissions were 9.34% and 0.25%, respectively. The penumbra of the square field was 6.2 mm in the X direction and 8.0 mm in the Y direction. The average penumbras of the rhombus fields with side lengths of 5 and 10 cm were 3.6 and 4.9 mm, respectively. For the right triangular and circular fields, the fields shaped by the dual-layer leaves were much closer to the set field than those shaped by single-layer leaves. The dose undulation amplitude of the 50% isodose lines and leaf stepping angle change of the dual-layer leaves were smaller than those of the single-layer leaves. CONCLUSIONS: The αMLC benefits from its orthogonal dual-layer design. Leaf transmission, dose undulations at the field edge, and MLC field dependence of the leaf stepping angle of the dual-layer αMLC were remarkably reduced.

Research and application progress of microbial ß-mannanases: a mini-review.

Mannan is a predominant constituent of cork hemicellulose and is widely distributed in various plant tissues. ß-Mannanase is the principal mannan-degrading enzyme, which breaks down the ß-1,4-linked mannosidic bonds in mannans in an endo-acting manner. Microorganisms are a valuable source of ß-mannanase, which exhibits catalytic activity in a wide range of pH and temperature, making it highly versatile and applicable in pharmaceuticals, feed, paper pulping, biorefinery, and other industries. Here, the origin, classification, enzymatic properties, molecular modification, immobilization, and practical applications of microbial ß-mannanases are reviewed, the future research directions for microbial ß-mannanases are also outlined.

Corn straw-saccharification fiber improved the reproductive performance of sows in the late gestation and lactation via lipid metabolism.

With the development of animal husbandry, the shortage of animal feedstuffs has become serious. Dietary fiber plays a crucial role in regulating animal health and production performance. The aim of this study was to investigate the effects of three kinds of corn straw-saccharification fibers (CSSF) such as high-fiber and low-saccharification (HFLS), medium-fiber and medium-saccharification (MFMS), low-fiber and high-saccharification (LFHS) CSSF on the reproductive performance of sows. Thirty-two primiparous Yorkshire sows were randomly assigned to 4 groups, 8 sows for each group. Group A was the basal diet as the control group; groups B - D were added with 6% HFLSCSSF, 6% MFMSCSSF and 6% LFHSCSSF to replace some parts of corn meal and wheat bran in the basal diet, respectively. The experimental period was from day 85 of gestation to the end of lactation (day 25 post-farrowing). The results showed that 6% LFHSCSSF addition significantly increased number of total born (alive) piglets, litter weight at birth (p < 0.05), whereas three kinds of CSSF significantly decreased backfat thickness of sows during gestation (p < 0.001), compared with the control group. Furthermore, CSSF improved the digestibility of crude protein, ether extract and fiber for sows. In addition, the levels of total cholesterol, total triglycerides, and high-density lipoprotein cholesterol in serum of sows were decreased by different kinds of CSSF. Further analysis revealed that CSSF regulated lipid metabolism through adjusting the serum metabolites such as 4-pyridoxic acid, phosphatidyl cholines and L-tyrosine. In summary, CSSF addition to the diets of sows during late gestation and lactation regulated lipid metabolism and improved reproductive performance of sows. This study provided a theoretical basis for the application of corn straw in sow diets.

Seizure as the main presenting manifestation of three patients with acute glufosinate-ammonium poisoning.

Glufosinate-ammonium herbicides are the most widely used broad-spectrum, non-selective herbicides in the world. Glufosinate-ammonium is a structural analogue of glutamate (Glu) which can irreversibly inhibit the activity of glutamine synthetase (GS) and Glu decarboxylase in plants, thereby blocking the synthesis of glutamine (Gln) from Glu and ammonia (Hoerlein, 1994). This causes the plants to die because of the nitrogen metabolism disorder and subsequent intracellular accumulation of ammonia. In humans, the characteristic features of glufosinate-ammonium herbicide poisoning include gastrointestinal symptoms and neurotoxicity (Watanabe and Sano, 1998). Currently, there are no antidotes for glufosinate-ammonium herbicide poisoning, and thus supportive care is the key treatment.

Brain imaging of a gamified cognitive flexibility task in young and older adults.

The study aimed to develop and validate a gamified cognitive flexibility task through brain imaging, and to investigate behavioral and brain activation differences between young and older adults during task performance. Thirty-one young adults (aged 18-35) and 31 older adults (aged 60-80) were included in the present study. All participants underwent fMRI scans while completing the gamified cognitive flexibility task. Results showed that young adults outperformed older adults on the task. The left inferior frontal junction (IFJ), a key region of cognitive flexibility, was significantly activated during the task in both older and young adults. Comparatively, the percent signal change in the left IFJ was stronger in older adults than in young adults. Moreover, older adults demonstrated more precise representations during the task in the left IFJ. Additionally, the left inferior parietal lobule (IPL) and superior parietal lobule in older adults and the left middle frontal gyrus (MFG) and inferior frontal gyrus in young adults were also activated during the task. Psychophysiological interaction analyses showed significant functional connectivity between the left IFJ and the left IPL, as well as the right precuneus in older adults. In young adults, significant functional connectivity was found between the left IFJ and the left MFG, as well as the right angular. The current study provides preliminary evidence for the validity of the gamified cognitive flexibility task through brain imaging. The findings suggest that this task could serve as a reliable tool for assessing cognitive flexibility and for exploring age-related differences of cognitive flexibility in both brain and behavior.

[Application status and challenges of molecular docking in development of traditional Chinese medicine].

Traditional Chinese medicine is precious treasure of ancient Chinese science and a key to unlocking the treasure trove of Chinese civilization. To elucidate the efficacy and mechanism of traditional Chinese medicines, scientists have been engaged in the research on the molecular basis and regulatory targets. Molecular docking is a computer-aided drug design method capable of visualizing the interaction between components and target proteins. With the progress in the modernization of traditional Chinese medicine and the advancement of algorithms and computing power, molecular docking has become an essential approach in the development of new traditional Chinese medicines. This article summarizes the recent research progress in molecular docking in the development of traditional Chinese medicine, aiming to provide valuable references for further screening of active components and offering insights for improving the development of new traditional Chinese medicines.

Hypoxia-Inducible Factor-1α Regulates High Phosphate-Induced Vascular Calcification via Type III Sodium-Dependent Phosphate Cotransporter 1.

Vascular calcification (VC) has a high incidence in patients with chronic kidney disease, which is a worldwide public health problem and presents a heavy burden to society. Hypoxia-inducible factor (HIF)-1α, the active subunit of HIF-1, has been reported to play a vital role in high phosphate-induced VC. However, the underlying mechanism is still undetermined, and effective treatment is unavailable. In the present study, human aortic smooth muscle cells (HASMCs) were cultured under normal or high phosphate media conditions. HIF-1α small interfering RNA and overexpression plasmids were employed to regulate HIF-1α expression. Phosphonoformic acid was employed to restrain the function of type III sodium-dependent phosphate cotransporter 1 (Pit-1). The expression levels of HIF-1α, Pit-1, runt-related transcription factor 2 (Runx2), and smooth muscle 22 alpha (SM22α) were evaluated, and the calcium contents were also examined. Cell growth was assessed using an MTT assay. High phosphate stimulation caused an upregulation in HIF-1α and Pit-1 expression levels and induced calcium depositions in HASMCs. Upregulation of Runx2 expression accompanied by downregulation of SM22α expression was observed in the high phosphate group. Following the suppression of HIF-1α expression, there was a concomitant attenuation in Pit-1 expression, calcium deposition, the alteration of phenotypic transition marker genes, and vice versa. The most serious calcium deposition was noted in HASMCs cultured under high phosphate conditions which were pretreated with a HIF-1α overexpression plasmid. However, when the biological functions of Pit-1 were restrained, the putative serious calcium deposition was not formed even in HASMCs transfected with a HIF-1α overexpression plasmid. The findings confirmed that HIF-1α regulated Pit-1 expression and exerted its pro-calcifying effect through Pit-1, which identified HIF-1α and Pit-1 as therapeutic targets for high phosphate-induced VC.

Confinement of Sustainable Carbon Dots Results in Long Afterglow Emitters and Photocatalyst for Radical Photopolymerization.

Sustainable carbon dots based on cellulose, particularly carboxymethyl cellulose (CMCCDs), were confined in an inorganic network resulting in CMCCDs@SiO2. This resulted in a material exhibiting long afterglow covering a time frame of several seconds also under air. Temperature-dependent emission spectra gave information on temperature-assisted delayed fluorescence (TADF) and room temperature phosphorescence (RTP) while photocurrent experiments provided a deeper understanding of charge availability in the dark period, and therefore, its availability on the photocatalyst surface. The photo-ATRP initiator, ethyl(bromo)phenyl acetate (EBPA), quenched the emission from the millisecond to the nanosecond time frame indicating participation of the triplet state in photoinduced electron transfer (PET). Both free radical and living radical polymerization based on photo-ATRP protocol worked successfully. Metal-free photo-ATRP resulted in chain extendable macroinitiators based on a reductive mechanism with either MMA or in combination with styrene. Addition of 9 ppm Cu2+ resulted in Mw/Mn of 1.4 while an increase to 72 ppm improved uniformity of the polymers; that is Mw/Mn=1.03. Complementary experiments with kerria laca confined materials, namely KCDs@SiO2, provided similar results. Deposition of Cu2+ (9 ppm) on the photocatalyst surface explains better uniformity of the polymers formed in the ATRP protocol.

Theoretical and experimental studies on channel impulse response of short-range non-line-of-sight ultraviolet communications.

A theoretical channel impulse response (CIR) model of short-range non-line-of-sight (NLOS) ultraviolet communications (UVC) in noncoplanar geometry under the single-scatter condition is proposed. Simulation results obtained from the widely accepted Monte-Carlo (MC)-based channel model of NLOS UVC are provided to verify corresponding theoretical results obtained from the proposed theoretical single-scatter CIR model. Additionally, an outdoor experiment with a light-emitting diode (LED) as the light source is first designed to measure the channel step response of NLOS UVC and to further validate the proposed theoretical single-scatter CIR model. By varying the different parameters of the transmitter and the receiver, such as the baseline range, the inclination angle, the azimuth angle, the beam divergence angle, and the field-of-view angle, the results of the proposed theoretical single-scatter CIR model and the MC-based channel model are exhibited and further analyzed in detail. Results indicate that the computational time cost by the proposed theoretical single-scatter CIR model is decreased to less than 0.6% of the MC-based one with comparable accuracy in assessing the temporal characteristics of NLOS UVC channels. Additionally, theoretical results obtained from the proposed theoretical single-scatter CIR model manifest satisfactory agreement with corresponding experimental measurements.

U-shaped relationship between fasting blood glucose and urinary albumin-to-creatinine ratio in the general United States population.

Objective: The current controversy surrounding the association between fasting blood glucose (FBG) and albuminuria necessitates further investigation. Hence, the primary objective of this study was to examine the relationship between FBG and urinary albumin-to-creatinine ratio (UACR). Methods: A cohort of complete data from National Health and Nutrition Examination Survey (NHANES) participants (1999-2020) was analyzed. Linear regression analyses and a generalized additive model explored the association between FBG and UACR. Furthermore, the stability of this relationship across different populations was assessed. Results: The study involved a total of 20,264 participants who were identified as U.S. citizens. By employing linear regression analysis, a statistically significant relationship was observed between elevated FBG levels and an increase in UACR (P<0.0001). Additionally, using a generalized additive model analysis, a U-shaped correlation between FBG and UACR was identified. Further examination using threshold effect analysis indicated a turning point for FBG at 5.44 mmol/L. A noteworthy finding in multiple populations is the consistent U-shaped association between FBG and UACR, except for individuals with serum uric acid levels ≥420 µmol/L and those who refrain from alcohol consumption. Conclusion: The general U.S. population has a U-shaped nonlinear relationship between FBG and UACR.

Temporal patterns of organ dysfunction in COVID-19 patients hospitalized in the intensive care unit: A group-based multitrajectory modelling analysis.

BACKGROUND: The course of organ dysfunction (OD) in Corona Virus Disease 2019 (COVID-19) patients is unknown. Herein, we analyse the temporal patterns of OD in intensive care unit-admitted COVID-19 patients. METHODS: Sequential organ failure assessment scores were evaluated daily within 2 weeks of admission to determine the temporal trajectory of OD using group-based multitrajectory modelling (GBMTM). RESULTS: 392 patients were enrolled with a 28-day mortality rate of 53.6%. GBMTM identified four distinct trajectories. Group 1 (mild OD, n=64), with a median APACHE II score of 13 (IQR 9-21), had an early resolution of OD and a low mortality rate. Group 2 (moderate OD, n=140), with a median APACHE II score of 18 (IQR 13-22), had a 28-day mortality rate of 30.0%. Group 3 (severe OD, n=117), with a median APACHR II score of 20 (IQR 13-27), had a deterioration trend of respiratory dysfunction and a 28-day mortality rate of 69.2%. Group 4 (extremely severe OD, n=71), with a median APACHE II score of 20 (IQR 17-27), had a significant and sustained OD affecting all organ systems and a 28-day mortality rate of 97.2%. CONCLUSIONS: Four distinct trajectories of OD were identified, and respiratory dysfunction trajectory could predict nonpulmonary OD trajectories and patient prognosis.

Visualized Enzyme-Activated Fluorescence Probe for Accurately Detecting ß-Gal in Living Cells and BALB/c Nude Mice.

Colorectal cancer was one of the major malignant tumors threatening human health and ß-Gal was recognized as a principal biomarker for primary colorectal cancer. Thus, designing specific and efficient quantitative detection methods for measuring ß-Gal enzyme activity was of great clinical test significance. Herein, an ultrasensitive detection method based on Turn-on fluorescence probe (CS-ßGal) was reported for visualizing the detection of exogenous and endogenous ß-galactosidase enzyme activity. The test method possessed a series of excellent performances, such as a significant fluorescence enhancement (about 11.3-fold), high selectivity as well as superior sensitivity. Furthermore, under the optimal experimental conditions, a relatively low limit of detection down to 0.024 U/mL was achieved for fluorescence titration experiment. It was thanks to the better biocompatibility and low cytotoxicity, CS-ßGal had been triumphantly employed to visual detect endogenous and exogenous ß-Gal concentration variations in living cells with noteworthy anti-interference performance. More biologically significant was the fact that the application of CS-ßGal in BALB/c nude mice was also achieved successfully for monitoring endogenous ß-Gal enzyme activity.

A facile cellulose finishing strategy through in-situ growth of sliver-doped manganese dioxide assisted by amine-quinone for improving indoor living quality.

Nowadays, various harmful indoor pollutants especially including bacteria and residual formaldehyde (HCHO) seriously threaten human health and reduce the quality of public life. Herein, a universal substrate-independence finishing approach for efficiently solving these hybrid indoor threats is demonstrated, in which amine-quinone network (AQN) was employed as reduction agent to guide in-situ growth of Ag@MnO2 particles, and also acted as an adhesion interlayer to firmly anchor nanoparticles onto diverse textiles, especially for cotton fabrics. In contrast with traditional hydrothermal or calcine methods, the highly reactive AQN ensures the efficient generation of functional nanoparticles under mild conditions without any additional catalysts. During the AQN-guided reduction, the doping of Ag atoms onto cellulose fiber surface optimized the crystallinity and oxygen vacancy of MnO2, providing cotton efficient antibacterial efficiency over 90 % after 30 min of contact, companying with encouraging UV-shielding and indoor HCHO purification properties. Besides, even after 30 cycles of standard washing, the Ag@MnO2-decorated textiles can effectively degrade HCHO while well-maintaining their inherent properties. In summary, the presented AQN-mediated strategy of efficiently guiding the deposition of functional particles on fibers has broad application prospects in the green and sustainable functionalization of textiles.

Trimethylamine-N-oxide aggravated the sympathetic excitation in D-galactose induced aging rats by down-regulating P2Y12 receptor in microglia.

This study aimed to determine whether trimethylamine N-oxide (TMAO) was involved in sympathetic activation in aging and the underlying mechanisms. Our hypothesis is TMAO reduces P2Y12 receptor (P2Y12R) and induces microglia-mediated inflammation in the paraventricular nucleus (PVN), then leading to sympathetic activation in aging. This study involved 18 young adults and 16 old adults. Aging rats were established by injecting D-galactose (D-gal, 200 mg/kg/d) subcutaneously for 12 weeks. TMAO (120 mg/kg/d) or 1% 3, 3-dimethyl-l-butanol (DMB) was administrated via drinking water for 12 weeks to investigate their effects on neuroinflammation and sympathetic activation in aging rats. Plasma TMAO, NE and IL-1ß levels were higher in old adults than in young adults. In addition, standard deviation of all normal to normal intervals (SDNN) and standard deviation of the average of normal to normal intervals (SDANN) were lower in old adults and negatively correlated with TMAO, indicating sympathetic activation in old adults, which is associated with an increase in TMAO levels. Treatment of rats with D-gal showed increased senescence-associated protein levels and microglia-mediated inflammation, as well as decreased P2Y12R protein levels in PVN. Plasma TMAO, NE and IL-1ß levels were increased, accompanied by enhanced renal sympathetic nerve activity (RSNA). While TMAO treatment exacerbated the above phenomenon, DMB mitigated it. These findings suggest that TMAO contributes to sympathetic hyperactivity in aging by downregulating P2Y12R in microglia and increasing inflammation in the PVN. These results may provide promising new target for the prevention and treatment of aging and aging-related diseases.

Revisiting the association between vitamin D deficiency and active tuberculosis: A prospective case-control study in Taiwan.

BACKGROUND: To revisit the association between vitamin D deficiency (VDD, defined as serum 25(OH)D < 20 ng/ml) and incident active tuberculosis (TB), after two potentially underpowered randomized trials showed statistically non-significant 13%-22% decrease in TB incidence in vitamin D supplementation groups. METHODS: We prospectively conducted an age/sex-matched case-control study that accounting for body-mass index (BMI), smoking, and other confounding factors to examine the association between VDD and active TB among non-HIV people in Taiwan (latitude 24°N), a high-income society which continues to have moderate TB burden. RESULTS: We enrolled 62 people with incident active TB and 248 people in control group. The TB case patients had a significantly higher proportion of VDD compared to the control group (51.6% vs 29.8%, p = 0.001). The 25(OH)D level was also significantly lower in TB patients compared to control group (21.25 ± 8.93 ng/ml vs 24.45 ± 8.36 ng/ml, p = 0.008). In multivariable analysis, VDD (adjusted odds ratio [aOR]: 3.03, p = 0.002), lower BMI (aOR: 0.81, p < 0.001), liver cirrhosis (aOR: 8.99, p = 0.042), and smoking (aOR: 4.52, p = 0.001) were independent risk factors for incident active TB. CONCLUSIONS: VDD is an independent risk factor for incident active TB. Future randomized trials examining the effect of vitamin D supplementation on TB incidence should focus on people with a low BMI or other risk factors to maximize the statistical power.

Synthesis, Plant Growth Regulatory Activity, and Transcriptome Analysis of Novel Opabactin Analogs.

Abscisic acid (ABA), a phytohormone, and its analogs have been found to enhance plant resistance to various biotic and abiotic stresses, particularly drought, by activating the ABA signaling pathway. This study used a combination of structure-directed design and molecular docking screening methods to synthesize a novel series of opabactin (OP) analogs. Among them, compounds 4a-4d and 5a showed comparable or superior activity to OP in bioassays, including seed germination and seedling growth inhibition in A. thaliana and rice, stomatal closure, and drought resistance in wheat and soybean. Further transcriptome analysis revealed distinct mechanisms of action between compound 4c and iso-PhABA in enhancing drought tolerance in A. thaliana. These findings highlight the application prospect of 4c and its analogs in agricultural cultivation, particularly in drought resistance. Additionally, they provide new insights into the mechanisms by which different ABA receptor agonists enhance drought resistance.

Anti-cancer mechanisms of natural isoflavones against melanoma.

The incidence of skin-related neoplasms has generally increased in recent years. Melanoma arises from malignant mutations in melanocytes in the basal layer of the epidermis and is a fatal skin cancer that seriously threatens human health. Isoflavones are polyphenolic compounds widely present in legumes and have drawn scientists' attention, because they have good efficacy against a variety of cancers, including melanoma, without significant toxic side effects and resistance. In this review article, we summarize the research progress of isoflavones in melanoma, including anti-melanoma roles and mechanisms of isoflavones via inhibition of tyrosinase activity, melanogenesis, melanoma cell growth, invasion of melanoma cells, and induction of apoptosis in melanoma cells. This information is important for the prevention, clinical treatment, and prognosis and survival of melanoma.

Microorganisms and bacterial cellulose stability of Kombucha under different manufacture and storage conditions.

It is crucial to clarify the stability of Kombucha in the manufacture and storage stages due to the extensive study on the fermented products of Kombucha and the increase in the use of bacterial cellulose (BC). This study aimed to evaluate the stability of Kombucha in different manufacturing and storage temperatures within a certain time period. The stability of microorganisms and BC in Kombucha was investigated through regular replacement with the tea media at 28 and 25°C for manufacture, and the storage temperature of Kombucha was at 25, 4, and -20°C. Morphological observations of the BC in Kombucha ended at 28 and 25°C for manufacture and storage were performed using atomic force microscopy (AFM) before inoculation. The viable cell counts and AFM results showed that the stability of Kombucha during manufacture was better at 28°C than at 25°C, with higher microbial viability and BC productivity in the former at the time of manufacture, whereas 25°C was more favorable for the stability of Kombucha during storage. At the same temperature of 25°C, the manufacturing practice improved the microbial viability and BC stability compared with storage; the pH value of Kombucha was lower, and the dry weight of BC was higher during storage compared with manufacture. The maximum BC water holding capacity (97.16%) was maintained by storage at 4°C on day 63, and the maximum BC swelling rate (56.92%) was observed after storage at -20°C on day 7. The research was conducted to provide reference information for applying Kombucha and its BC in food and development in other industries.