Metabolism and distribution of two major constituents of 'Xing-Nao-Jing Injection'-germacrone and curdione in rats.

Germacrone and curdione are germacrane-type sesquiterpenoids that are widely distributed and have extensive pharmacological activities; they are the main constituents of 'Xing-Nao-Jing Injection' (XNJ). Studies on the metabolic features of germacrane-type sesquiterpenoids are limited. In this study, the metabolites of germacrone and curdione were characterized by UHPLC-Q-Exactive Oribitrap mass spectrometry after they were orally administered to rats. In total, 60 and 76 metabolites were found and preliminarily identified in rats administered germacrone and curdione, respectively, among which at least 123 potential new compounds were included. New metabolic reactions of germacrane-type sesquiterpenoids were identified, which included oxidation (+4 O and +5 O), ethylation, methyl-sulfinylation, vitamin C conjugation, and cysteine conjugation reactions. Among the 136 metabolites (including 113 oxidation metabolites, two glucuronidation, two methylation, nine methyl-sulfinylation, three ethylation, six cysteine conjugation, and one Vitamin C conjugation metabolites), 32 metabolites were detected in nine organs, and the stomach, intestine, liver, kidneys, and small intestine were the main organs for the distribution of these metabolites. All 136 metabolites were detected in urine and 64 of them were found in feces. The results of this study not only contribute to research on in vivo processes related to germacrane-type sesquiterpenoids but also provide a strong foundation for a better understanding of in vivo processes and the effective forms of germacrone, curdione, and XNJ.

Benzothiadiazole-Based Ordered Mesoporous Polymer as a Versatile, Metal-Free Heterogeneous Photocatalyst.

Visible-light active heterogeneous organophotocatalysts have recently gained considerable interest in organic synthetic community. Ordered mesoporous polymers (OMPs) are highly promising as heterogeneous alternative to traditional precious metal/organic dyes-based photocatalysts. Herein, we report the preparation of a benzothiadiazole functionalized OMPs (BT-MPs) through a "bottom-up" strategy. High ordered periodic porosity, large surface area, excellent stability and rational energy-band structures guarantee the high catalytic activity of BT-MPs. As a result, at least six conversions, e.g., the [3+2] cycloaddition of phenols with olefins, the selective oxidation of sulfides, the C-3 thiocyanation of indole and the aminothiocyanation of ß-keto ester, could be promoted smoothly by BT-MPs. In addition, BT-MPs was readily recovered with well maintaining its photocatalytic activity and could be reused for at least eight times. This study highlights the potential of exploiting photoactive OMPs as recyclable, robust and metal-free heterogeneous photocatalysts.

USP19 Stabilizes TAK1 to Regulate High Glucose/Free Fatty Acid-induced Dysfunction in HK-2 Cells.

OBJECTIVE: Obesity-induced kidney injury contributes to the development of diabetic nephropathy (DN). Here, we identified the functions of ubiquitin-specific peptidase 19 (USP19) in HK-2 cells exposed to a combination of high glucose (HG) and free fatty acid (FFA) and determined its association with TGF-beta-activated kinase 1 (TAK1). METHODS: HK-2 cells were exposed to a combination of HG and FFA. USP19 mRNA expression was detected by quantitative RT-PCR (qRT-PCR), and protein analysis was performed by immunoblotting (IB). Cell growth was assessed by Cell Counting Kit-8 (CCK-8) viability and 5-ethynyl-2'-deoxyuridine (EdU) proliferation assays. Cell cycle distribution and apoptosis were detected by flow cytometry. The USP19/TAK1 interaction and ubiquitinated TAK1 levels were assayed by coimmunoprecipitation (Co-IP) assays and IB. RESULTS: In HG+FFA-challenged HK-2 cells, USP19 was highly expressed. USP19 knockdown attenuated HG+FFA-triggered growth inhibition and apoptosis promotion in HK-2 cells. Moreover, USP19 knockdown alleviated HG+FFA-mediated PTEN-induced putative kinase 1 (PINK1)/Parkin pathway inactivation and increased mitochondrial reactive oxygen species (ROS) generation in HK-2 cells. Mechanistically, USP19 stabilized the TAK1 protein through deubiquitination. Importantly, increased TAK1 expression reversed the USP19 knockdown-mediated phenotypic changes and PINK1/Parkin pathway activation in HG+FFA-challenged HK-2 cells. CONCLUSION: The findings revealed that USP19 plays a crucial role in promoting HK-2 cell dysfunction induced by combined stimulation with HG and FFAs by stabilizing TAK1, providing a potential therapeutic strategy for combating DN.

Effect of polyethylene terephthalate plastics on nitrogen, sulphur and chlorine contaminants via sludge pyrolysis and Pb/Cu adsorption properties of biochar.

Pyrolysis is an effective process for disposing of municipal sewage sludge (SS). Plastics can affect the SS pyrolysis behaviour and pyrolysis products due to their low ash and high hydrocarbon ratio. The secondary pollutants from the pyrolysis process may also be affected. Therefore, polyethylene terephthalate (PET), a typical plastic, was chosen to investigate the release characteristics of pollutants containing nitrogen, sulphur, and chlorine via SS pyrolysis, and the changes of biochar to adsorb two typical heavy metals, Pb and Cu. The pyrolysis of PET plastics facilitates the migration of N toward solid and liquid-phase products, S and Cl to the gas-phase products via pyrolysis. Oxygenated compounds of pyrolytic volatiles decreased from 38.18% to 28.43%, concurrently promoting the formation of phenolic compounds. The co-pyrolysis improved the quality of biochar and the ability to adsorb Pb and Cu. This systematic study can provide some support for the further improvement of SS pyrolysis technology, and will also be beneficial for subsequent applications.

Pore Environmental Modification by Amino Groups in Robust Microporous MOFs for SF6 Capturing and SF6/N2 Separation.

Capturing and separating the greenhouse gas SF6 from nitrogen N2 have significant greenhouse mitigation potential and economic benefits. We used a pore engineering strategy to manipulate the pore environment of the metal-organic framework (MOF) by incorporating organic functional groups (-NH2). This resulted in an enhanced adsorption of SF6 and separation of the SF6/N2 mixture in the MOF. The introduction of amino (-NH2) groups into YTU-29 resulted in a reduction of the Brunauer-Emmett-Teller surface but an increase in interactions with SF6 within the confined pores. Water-stable YTU-29-NH2 showed a significantly higher SF6 uptake (95.5 cm3/g) than YTU-29 (77.4 cm3/g). The results of the breakthrough experiments show that YTU-29-NH2 has a significantly improved separation performance for SF6/N2 mixtures, with a high SF6 capture of 0.88 mmol/g compared to 0.56 mmol/g by YTU-29. This improvement is due to the suitable pore confinement and accessible -NH2 groups on pore surfaces. Considering its excellent regeneration ability and cycling performance, ultrastable YTU-29-NH2 demonstrates great potential for SF6 capturing and SF6/N2 separation.

Moiré fringe imaging of heterostructures by scanning transmission electron microscopy.

A heterostructured crystalline bilayer specimen is known to produce moiré fringes (MFs) in the conventional transmission electron microscopy (TEM). However, the understanding of how these patterns form in scanning transmission electron microscopy (STEM) remains limited. Here, we extended the double-scattering model to establish the imaging theory of MFs in STEM for a bilayer sample and applied this theory to successfully explain both experimental and simulated STEM images of a perovskite PbZrO3/SrTiO3 system. Our findings demonstrated that the wave vectors of electrons exiting from Layer-1 and their relative positions with the atomic columns of Layer-2 should be taken into account. The atomic column misalignment leads to a faster reduction in the intensity of the secondary scattering beam compared to the single scattering beam as the scattering angle increases. Consequently, the intensity distribution of MFs in the bright field (BF)-STEM can be still described as the product of two single atomic images. However, in high angle annular dark field (HAADF)-STEM, it is approximately described as the superposition of the two images. Our work not only fills a knowledge gap of MFs in incoherent imaging, but also emphasizes the importance of the coherent scattering restricted by the real space when analyzing the HAADF-STEM imaging.

Traditional Chinese exercise in chronic obstructive pulmonary disease: An overview of systematic reviews.

This study aims to critically reassess existing systematic reviews (SR) on Traditional Chinese Exercises (TCE) for treating Chronic Obstructive Pulmonary Disease (COPD). The primary objectives include synthesizing available evidence, evaluating the methodological quality of reviews and overall evidence, and providing comprehensive insights into the effectiveness of different TCE types in managing COPD. Sinomed, CNKI, VIP, Wanfang, PubMed, Cochrane Library, and Web of Science were searched from inception to April 2023 for SR literature on the treatment of COPD with TCE. The extracted data from the included SRs encompassed various aspects such as general information, study population, intervention measures, meta-analysis results, and conclusions. The methodological quality of the included SRs was assessed using the AMSTAR II tool. Additionally, the GRADE tool was used to determine the evidence level of outcome indicators. This study included 17 SRs and 4 types of TCE. The CCA was 0.041, indicating a slight overlap between the primary studies. Notably, one study was rated as low quality on the AMSTAR II scale, while the rest were classified as critically low quality. The results from the GRADE evaluation revealed 26 pieces of very low-quality evidence, 55 pieces of low-quality evidence, and 17 pieces of moderate-quality evidence. The moderate-quality evidence suggests that Liuzijue effectively improves TCM syndrome scores in patients with COPD. Additionally, low-quality evidence suggests that Liuzijue improves patients' lung function (FEV1, FVC) and quality of life (CAT, MRC/mMRC). Similarly, low-quality evidence suggests that Baduanjin can improve patients' lung function (FEV1%, FVC) and quality of life (SGRQ). Low-quality evidence also suggests that Health Qigong can significantly improve patients' exercise endurance (6MWD). No SR reported TCE-related adverse reactions. TCE interventions are effective and safe in the treatment of COPD. Different types of TCE have varying effects on outcomes in COPD patients. However, these findings are limited by the generally low methodological and evidence quality of the included SRs. Therefore, it is strongly recommended to improve study designs to obtain higher-quality clinical evidence and to strictly follow SR protocols.

Lipid-Laden Macrophages in Pulmonary Diseases.

Pulmonary surfactants play a crucial role in managing lung lipid metabolism, and dysregulation of this process is evident in various lung diseases. Alternations in lipid metabolism lead to pulmonary surfactant damage, resulting in hyperlipidemia in response to lung injury. Lung macrophages are responsible for recycling damaged lipid droplets to maintain lipid homeostasis. The inflammatory response triggered by external stimuli such as cigarette smoke, bleomycin, and bacteria can interfere with this process, resulting in the formation of lipid-laden macrophages (LLMs), also known as foamy macrophages. Recent studies have highlighted the potential significance of LLM formation in a range of pulmonary diseases. Furthermore, growing evidence suggests that LLMs are present in patients suffering from various pulmonary conditions. In this review, we summarize the essential metabolic and signaling pathways driving the LLM formation in chronic obstructive pulmonary disease, pulmonary fibrosis, tuberculosis, and acute lung injury.

Dynamic changes and the effects of key procedures on the characteristic aroma compounds of Lu'an Guapian green tea during the manufacturing process.

As a kind of green tea with unique multiple baking processes, the flavor code of Lu'an Guapian (LAGP) has recently been revealed. To improve and stabilize the quality of LAGP, further insight into the dynamic changes in odorants during the whole processing is required. In this study, 50 odorants were identified in processing tea leaves, 14 of which were selected for absolute quantification to profile the effect of processes. The results showed that spreading is crucial for key aroma generation and accumulation, while these odorants undergo significant changes at the deep baking stage. By adjusting the conditions of the spreading and deep baking, it was found that low-temperature (4 °C) spreading for 6 h and low-temperature with long-time baking (final leaf temperature: 102 °C, 45 min) could improve the overall aroma quality. These results provide a new direction for enhancing the quality of LAGP green tea.

Differentiation of three commercial tuna species through GC-Q-TOF and UPLC-Q/Orbitrap mass spectrometry-based metabolomics and chemometrics.

Food fraud is common in the tuna industry because of the economic benefits involved. Ensuring the authenticity of tuna species is crucial for protecting both consumers and tuna stocks. In this study, GC-Q-TOF and UPLC-Q/Orbitrap mass spectrometry-based metabolomics were used to investigate the metabolite profiles of three commercial tuna species (skipjack tuna, bigeye tuna and yellowfin tuna). A total of 22 and 77 metabolites were identified with high confidence using GC-Q-TOF and UPLC-Q/Orbitrap mass spectrometry, respectively. Further screening via chemometrics revealed that 38 metabolites could potentially serve as potential biomarkers. Hierarchical cluster analysis showed that the screened metabolite biomarkers successfully distinguished the three tested tuna species. Furthermore, a total of 27 metabolic pathways were identified through enrichment analysis based on the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways.

Unraveling the Molecular Regulation of Ferroptosis in Respiratory Diseases.

Ferroptosis, a type of programmed cell death that relies on iron, is distinct in terms of its morphological, biochemical and genetic features. Unlike other forms of cell death, such as autophagy, apoptosis, necrosis, and pyroptosis, ferroptosis is primarily caused by lipid peroxidation. Cells that die due to iron can potentially trigger an immune response which intensifies inflammation and causes severe inflammatory reactions that eventually lead to multiple organ failure. In recent years, ferroptosis has been identified in an increasing number of medical fields, including neurological pathologies, chronic liver diseases and sepsis. Ferroptosis has the potential to cause an inflammatory tempest, with many of the catalysts and pathological indications of respiratory ailments being linked to inflammatory reactions. The growing investigation into ferroptosis in respiratory disorders has also garnered significant interest to better understand the mechanism of ferroptosis in these diseases. In this review, the recent progress in understanding the molecular control of ferroptosis and its mechanism in different respiratory disorders is examined. In addition, this review discusses current challenges and prospects for understanding the link between respiratory diseases and ferroptosis.

Copper-Bearing Metal-Organic Framework with Mucus-Penetrating Function for the Multi-Effective Clearance of Mucosal Colonized Helicobacter pylori.

Helicobacter pylori colonizes over 50% of people worldwide. Biofilm formation through penetrating gastric mucus and resistance acquired by H. pylori markedly reduces the efficacy of traditional antibiotics. The present triple therapy and bismuth-based quadruple therapy inevitably causes intestinal flora disturbance and fails to address the excessive H. pylori-triggered inflammatory response. Herein, a mucus-permeable therapeutic platform (Cu-MOF@NF) that consists of copper-bearing metal-organic framework (Cu-MOF) loaded with nitrogen-doped carbon dots and naturally active polysaccharide fucoidan is developed. The experimental results demonstrate that Cu-MOF@NF can penetrate the mucus layer and hinder H. pylori from adhering on gastric epithelial cells of the stomach. Notably, released Cu2+ can degrade the polysaccharides in the biofilm and interfere with the cyclic growing mode of "bacterioplankton ↔ biofilm", thereby preventing recurrent and persistent infection. Compared with traditional triple therapy, the Cu-MOF@NF not only possesses impressive antibacterial effect (even include multidrug-resistant strains), but also improves the inflammatory microenvironment without disrupting the balance of intestinal flora, providing a more efficient, safe, and antibiotic-free new approach to eradicating H. pylori.

Constructing Ru-O-TM Bridge in NiFe-LDH Enables High Current Hydrazine-assisted H2 Production.

Hydrazine oxidation-assisted water splitting is a critical technology to tackle the high energy consumption in large-scale H2 production. Ru-based electrocatalysts hold promise for synergetic hydrogen reduction (HER) and hydrazine oxidation (HzOR) catalysis but are hindered by excessive superficial adsorption of reactant intermediate. Herein, this work designs Ru cluster anchoring on NiFe-LDH (denoted as Ruc/NiFe-LDH), which effectively enhances the intermediate adsorption capacity of Ru by constructing Ru─O─Ni/Fe bridges. Notably, it achieves an industrial current density of 1 A cm-2 at an unprecedentedly low voltage of 0.43 V, saving 3.94 kWh m-3 H2 in energy, and exhibits remarkable stability over 120 h at a high current density of 5 A cm-2. Advanced characterizations and theoretical calculation reveal that the presence of Ru─O─Ni/Fe bridges widens the d-band width (Wd) of the Ru cluster, leading to a lower d-band center and higher electron occupation on antibonding orbitals, thereby facilitating moderate adsorption energy and enhanced catalytic activity of Ru.

Discrimination of three commercial tuna species through species-specific peptides: From high-resolution mass spectrometry discovery to MRM validation.

The risk of tuna adulteration is high driven by economic benefits. The authenticity of tuna is required to protect both consumers and tuna stocks. Given this, the study is designed to identify species-specific peptides for distinguishing three commercial tropical tuna species. The peptides derived from trypsin digestion were separated and detected using ultrahigh-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF/MS) in data-dependent acquisition (DDA) mode. Venn analysis showed that there were differences in peptide composition among the three tested tuna species. The biological specificity screening through the National Center for Biotechnology Information's Basic Local Alignment Search Tool (NCBI BLAST) revealed that 93 peptides could serve as potential species-specific peptides. Finally, the detection specificity of species-specific peptides of raw meats and processed products was carried out by multiple reaction monitoring (MRM) mode based on a Q-Trap mass spectrometer. The results showed that three, one and two peptides of Katsuwonus pelamis, Thunnus obesus and Thunnus albacores, respectively could serve as species-specific peptides.

Polar Bloch points in strained ferroelectric films.

Topological domain structures have drawn great attention as they have potential applications in future electronic devices. As an important concept linking the quantum and classical magnetism, a magnetic Bloch point, predicted in 1960s but not observed directly so far, is a singular point around which magnetization vectors orient to nearly all directions. Here we show polar Bloch points in tensile-strained ultrathin ferroelectric PbTiO3 films, which are alternatively visualized by phase-field simulations and aberration-corrected scanning transmission electron microscopic imaging. The phase-field simulations indicate local steady-state negative capacitance around the Bloch points. The observation of polar Bloch points and their emergent properties consequently implies novel applications in future integrated circuits and low power electronic devices.

Future proofing of chondroitin sulphate production: Importance of sustainability and quality for the end-applications.

Chondroitin sulphates (CSs) are the most well-known glycosaminoglycans (GAGs) found in any living organism, from microorganisms to invertebrates and vertebrates (including humans), and provide several health benefits. The applications of CSs are numerous including tissue engineering, osteoarthritis treatment, antiviral, cosmetics, and skincare applications. The current commercial production of CSs mostly uses animal, bovine, porcine, and avian tissues as well as marine organisms, marine mammals, sharks, and other fish. The production process consists of tissue hydrolysis, protein removal, and purification using various methods. Mostly, these are chemical-dependent and are complex, multi-step processes. There is a developing trend for abandonment of harsh extraction chemicals and their substitution with different green-extraction technologies, however, these are still in their infancy. The quality of CSs is the first and foremost requirement for end-applications and is dependent on the extraction and purification methodologies used. The final products will show different bio-functional properties, depending on their origin and production methodology. This is a comprehensive review of the characteristics, properties, uses, sources, and extraction methods of CSs. This review emphasises the need for extraction and purification processes to be environmentally friendly and gentle, followed by product analysis and quality control to ensure the expected bioactivity of CSs.

Asparaginase-specific basophil recognition and activation predict Asparaginase hypersensitivity in mice.

Background: Asparaginase (ASNase) is a crucial part of acute leukemia treatment, but immune responses to the agent can reduce its effectiveness and increase the risk of relapse. Currently, no reliable and validated biomarker predicts ASNase-induced hypersensitivity reactions during therapy. We aimed to identify predictive biomarkers and determine immune cells responsible for anaphylaxis using a murine model of ASNase hypersensitivity. Methods: Our preclinical study uses a murine model to investigate predictive biomarkers of ASNase anaphylaxis, including anti-ASNase antibody responses, immune complex (IC) levels, ASNase-specific binding to leukocytes or basophils, and basophil activation. Results: Our results indicate that mice immunized to ASNase exhibited dynamic IgM, IgG, and IgE antibody responses. The severity of ASNase-induced anaphylaxis was found to be correlated with levels of IgG and IgE, but not IgM. Basophils from immunized mice were able to recognize and activate in response to ASNase ex vivo, and the extent of recognition and activation also correlated with the severity of anaphylaxis observed. Using a multivariable model that included all biomarkers significantly associated with anaphylaxis, independent predictors of ASNase-induced hypersensitivity reactions were found to be ASNase IC levels and ASNase-specific binding to leukocytes or basophils. Consistent with our multivariable analysis, we found that basophil depletion significantly protected mice from ASNase-induced hypersensitivity reactions, supporting that basophils are essential and can be used as a predictive marker of ASNase-induced anaphylaxis. Conclusions: Our study demonstrates the need for using tools that can detect both IC- and IgE-mediated hypersensitivity reactions to mitigate the risk of ASNase-induced hypersensitivity reactions during treatment.

Comparative transcriptomic analysis reveals the molecular changes of acute pancreatitis in experimental models.

BACKGROUND: Acute pancreatitis (AP) encompasses a spectrum of pancreatic inflammatory conditions, ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure. Given the challenges associated with obtaining human pancreatic samples, research on AP predominantly relies on animal models. In this study, we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models. AIM: To investigate the shared molecular changes underlying the development of AP across varying severity levels. METHODS: AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide (LPS). Additionally, using Ptf1α to drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J- hM3/Ptf1α(cre) mice were administered Clozapine N-oxide to induce AP. Subsequently, we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus (GEO) database. RESULTS: Caerulein-induced AP showed severe inflammation and edema, which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis. Compared with the control group, RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model. Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway, TLR signaling pathway, and NF-κB signaling pathway, alongside elevated levels of apoptosis-related pathways, such as apoptosis, P53 pathway, and phagosome pathway. The significantly elevated genes in the TLR and NOD-like receptor signaling pathways, as well as in the apoptosis pathway, were validated through quantitative real-time PCR experiments in animal models. Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood, while TLR1, TLR7, RIPK3, and OAS2 genes exhibited marked elevation in human AP. The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP. The transgenic mouse model hM3/Ptf1α(cre) successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway, indicating that these pathways represent shared pathological processes in AP across different models. CONCLUSION: The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP, notably the MYD88 gene. Apoptosis holds a central position in the necrotic processes of AP, with TUBA1A and GADD45A genes exhibiting prominence in human AP.

Unraveling the Enantiomeric Distribution of Glycosidically Bound Linalool in Teas (Camellia sinensis) and Their Acidolysis Characteristics and Pyrolysis Mechanism.

Glycosidically bound linalool plays important roles in the formation of excellent tea flavor, while their enantiomeric distribution in teas and the actual transformations with free linalool are still unclear. In this study, a novel chiral ultrahigh performance liquid chromatography-mass spectrometry/mass spectrometry approach to directly analyze linalyl-ß-primeveroside and linalyl-ß-d-glucopyranoside enantiomers in teas was established and then applied in 30 tea samples. A close transformation relationship existed between the two states of linalool for their consistent dominant configurations (most S-form) and corresponding distribution trend in most teas (r up to 0.81). The acidolysis characterization indicated that free linalool might be slowly released from linalyl-ß-primeveroside with stable enantiomeric ratios during long-term withering of white tea in a weakly acidic environment, along with other isomerized products, e.g., geraniol, nerol, α-terpineol, etc. Furthermore, a novel online thermal desorption-gas chromatography-mass spectrometry approach was established to simulate the pyrolysis releasing of linalyl-ß-primeveroside during tea processing. Interestingly, free linalool was not the selected pyrolysis product of linalyl-ß-primeveroside but rather trans/cis-2,6-dimethyl-2,6-octadiene during the high-fire roasting or baking step of oolong and green teas. The identification of above high-fire chemical marks presented great potential to scientifically evaluate the proper thermal conditions in the practical production of tea.