Maternal exposure to Di-n-butyl phthalate (DBP) inhibit orexin receptor 1 (OX1R) expression to prevent Sertoli cells proliferation through the AKT signaling pathway.

BACKGROUND: Studies have demonstrated that Sertoli cells are the direct target of Dibutyl phthalate (DBP). However, the role of neurotransmitter receptors is not elucidated. METHODS: Based on our previous studies, maternal Sprague-Dawley (SD) rats in Gestation Day (GD) 14-18 and TM4 cells exposure to 750 mg/kg/day and 100 µM DBP were regarded as treated groups. Firstly, qRT-PCR array was used to determine the different expression of neurotransmitter receptors. We examined the OX1R expression on Rats in Control and DBP groups by immunohistochemistry. Real-time PCR and Western Blot were used to detect the protein and mRNA expression levels of OX1R in vivo and in vitro. The potential downstream signaling pathways were explored by analyzing the GSE99690 cohort. In addition, we extracted Primary Sertoli Cells (PSCs) from the testis of control group. The apoptosis-related proteins, AKT signaling pathway-related proteins and mRNA expressions were detected by Western Blot and Real-time PCR in PSCs. The validity of PSCs was measured by CCK-8 assay and flow cytometric analysis was used to demonstrate the apoptotic rates of PSCs after DBP exposure. RESULTS: The Orexin receptor 1 (OX1R) was screened out by qRT-PCR array. Our results showed that DBP could significantly suppress the OX1R expression of Sertoli cells in vivo and in vitro. Functional analysis showed the AKT signaling pathway was mediated by OX1R. The highly expressed apoptosis level and impaired cell activity were observed in PSCs, which can be reversed by Orexin A. Meanwhile, the p-AKT signaling pathway were hindered after DBP exposure while rescued in DBP + Orexin-A group. CONCLUSIONS: DBP can induce Sertoli cell apoptosis through its toxicological effect by suppressing OX1R and p-AKT expression, which provide a novel insight on the role of neurotransmitter receptors.

Chemical Constituents from the Whole Plants of Limonium sinense and Their in vitro Anti-inflammatory Activity.

The Yellow River Delta possesses lots of characteristic medicinal plants due to its high salinity and high alkaline environment and Limonium sinense is an iconic plant. However, there are very few studies on L. sinense and its chemical constituents have not been investigated in recent ten years. In the present study, the chemical constituents and bioactivities of L. sinense were fully studied for the first time. UPLC-MS/MS method combined with database comparison identified 109 compounds mainly including flavonoids, alkaloids and polyphenols. In addition, the potential bioactivities of L. sinense were considerated as anti-inflammatory, anti-oxidative, anti-tumor, hepatoprotective and hpyerglycemic activities based on these identified compounds and their related literature. Furthermore, four derivatives of 12-oxo-phytodienoic acid and butenolide including two new ones (1 and 2) were isolated from the whole plants of L. sinense. Their structures, including the absolute configurations, were determined by the analysis of comprehensive spectroscopic data. All isolates were evaluated for their anti-inflammatory activity. Compound 1 exhibited moderate anti-inflammatory activity with IC50 value of 37.5 ± 1.2 µM on NO production level.

Genetic diseases are not necessarily inherited: suggestion on its Chinese translation.

From Mendel's discovery of the basic laws of genetics in 1865 to the widespread application of genomics in medicine today, medical genetics has made enormous progress, and the concept of genetic diseases has also been evolved. In 1972, the World Health Organization (WHO) expert group began to use "Genetic Disease" to define hereditary diseases, while early Chinese genetics textbooks used "inferior inheritance", and later introduced terms such as "Genetic Disease" and "Inherited Disease". In the early days, it was generally believed that genetic diseases were inherited from ancestors. However, research in recent years has found that genetic diseases are not necessarily inherited, and some diseases are actually caused by de novo mutations in the offspring. Although the occurrence of this type of genetic disease is related to genetic factors, it is not inherited from ancestors. If we still use "Inherited Disease" or "Hereditary Disease" to describe it, it is not accurate enough. In order to further standardize the translation and use of the concept of "Genetic Disease", this article briefly reviews its development process in both English and Chinese literature, discusses the difference between different Chinese translations, and provides guidance and suggestions for scientifically and accurately describing genetic diseases in Chinese, with a view to promote efficient exchange and cooperation in the field of medical genetics.

New CDDO Arylboronate Ester Derivatives with High Selectivity and Low Toxicity.

As an oleanolic acid derivative, CDDO-Me lacks selectivity for tumors. Based on the high reactive oxygen species (ROS) level in cancer cells, compound 4 was selected from 17 new CDDO arylboronate ester derivatives. A preliminary study revealed that 4 displayed the highest selectivity for cancer cells. Furthermore, 4 could be transformed to 4H by ROS to increase its covalent binding ability and antiproliferation effect (IC50 of 2.11 vs 0.37 µM) in BGC-823 cells. Interestingly, 4 increased ROS levels to induce apoptosis in BGC-823 cells. Moreover, the LD50 of 4 (91.2 mg/kg) was much greater than that of CDDO-Me (61.7 mg/kg) in ICR mice. A pharmacokinetic study indicated that 4 could be transformed to 4H in vivo. In addition, 4 exhibited a greater tumor inhibition rate (86.2%) than CDDO-Me (51.7%). Overall, the design of 4 provided an effective modification strategy for CDDO to increase the selectivity for cancer cells.

Exploring alkali-treated corn cob for high-rate removal of NOX and SO2 from flue gas: Focus on carbon release capacity, removal performance, and comparison with conventional carbon sources.

This investigation explored the potential of utilizing alkali-treated corn cob (CC) as a solid carbon source to improve NOX and SO2 removal from flue gas. Leaching experiments unveiled a hierarchy of chemical oxygen demand release capacity: 0.03 mol/L alkali-treated CC > 0.02 mol/L > 0.01 mol/L > 0.005 mol/L > control. In NOX and SO2 removal experiments, as the inlet NOX concentration rose from 300 to 1000 mg/m3, the average NOX removal efficiency increased from 58.56 % to 80.00 %. Conversely, SO2 removal efficiency decreased from 99.96 % to 91.05 %, but swiftly rebounded to 98.56 % by day 18. The accumulation of N intermediates (NH4+, NO3-, NO2-) increased with escalating inlet NOX concentration, while the accumulation of S intermediates (SO42-, SO32-, S0) varied based on shifts in the population of functional bacteria. The elevation in inlet NOX concentration stimulated the growth of denitrifying bacteria, enhancing NOX removal efficiency. Concurrently, the population of nitrate-reducing sulfur-oxidizing bacteria and sulfate-reducing bacteria expanded, aiding in the accumulation of S0 and the removal of SO2. The comparison experiments on carbon sources confirmed the comparable NOX and SO2 removal efficiencies of alkali-treated CC and glucose, yet underscored differences in intermediates accumulation due to distinct genus structures.

NAD+ Metabolism Reprogramming Mediates Irradiation-Induced Immunosuppressive Polarization of Macrophages.

PURPOSE: Radiation therapy stands as an important complementary treatment for head and neck squamous cell carcinoma (HNSCC), yet it does not invariably result in complete tumor regression. The infiltration of immunosuppressive macrophages is believed to mediate the radiation therapy resistance, whose mechanism remains largely unexplored. This study aimed to elucidate the role of immunosuppressive macrophages during radiation therapy and the associated underlying mechanisms. METHODS AND MATERIALS: Male C3H mice bearing syngeneic SCC-VII tumor received irradiation (2 × 8 Gy). The impact of irradiation on tumor-infiltrating macrophages was assessed. Bone marrow-derived macrophages were evaluated in differentiation, proliferation, migration, and inflammatory cytokines after treatment of irradiated tumor culture medium and irradiated tumor-derived extracellular vesicles (irTEVs). A comprehensive metabolomics profiling of the irTEVs was conducted using liquid chromatography-mass spectrometry, whereas key metabolites were investigated for their role in the mechanism of immunosuppression of macrophages in vitro and in vivo. RESULTS: Radiation therapy on SCC-VII syngeneic graft tumors increased polarization of both M1 and M2 macrophages in the tumor microenvironment and drove infiltrated macrophages toward an immunosuppressive phenotype. Irradiation-induced polarization and immunosuppression of macrophages were dependent on irTEVs which delivered an increased amount of niacinamide (NAM) to macrophages. NAM directly bound to the nuclear factor kappa-B transcriptional activity regulator USP7, through which NAM reduced translocation of nuclear factor kappa-B into the nucleus, thereby decreasing the release of cytokines interleukin 6 and interleukin 8. Increased enzyme activity of NAM phosphoribosyl transferase which is the rate-limiting enzyme of NAD+ metabolism, contributed to the irradiation-induced accumulation levels of NAM in irradiated HNSCC and irTEVs. Inhibition of NAM phosphoribosyl transferase decreased NAM levels in irTEVs and increased radiation therapy sensitivity by alleviating the immunosuppressive function of macrophages. CONCLUSIONS: Radiation therapy could induce NAD+ metabolic reprogramming of HNSCC cells, which regulate macrophages toward an immunosuppressive phenotype. Pharmacologic targeting of NAD+ metabolism might be a promising strategy for radiation therapy sensitization of HNSCC.

Comparative study on chemical constituents of different medicinal parts of Lonicera japonica Thunb. Based on LC-MS combined with multivariate statistical analysis.

Lonicerae japonicae flos (LJF), Lonicerae japonicae caulis (LJC), Lonicerae folium (LF) and Lonicerae fructus (LFR) are derived from Lonicera japonica Thunb., which are formed due to different medicinal parts. The efficacy of the 4 medicinal materials has similarities and differences. However, little attention has been paid to illustrate the differences in efficacy from the perspective of phytochemistry. In this study, ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry (UPLC-Q-Exactive-Orbitrap-MS) was used to qualitatively analyze the ingredients in 4 herbs. A total of 86 compounds were plausibly or unambiguously identified, there were 54 common components among the 4 medicinal materials, and each kind of medicinal materials had its own unique components. On the basis of qualitative analysis, ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UPLC-QQQ-MS/MS) was used to quantitatively analyze 31 components contained in 4 medicinal materials, and principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA) and other multivariate statistical analysis were furtherly performed for comparing the component contents. The results showed that the samples from the same parts were clustered into one group, and the samples from different medicinal parts were significantly different. The analysis of variable importance projection (VIP) value of the OPLS-DA model showed that 10 components including chlorogenic acid, secologanic acid, isochlorogenic acid A, loganin, lonicerin, loganic acid, secoxyloganin, sweroside, luteolin and rhoifolin were the main difference components among the 4 medicinal materials. The study not only lays a solid foundation for the intrinsic quality control of 4 medicinal materials and the study of different effects of the 4 medicinal materials at the phytochemical level, but also provides a basis for more rational utilization of various parts of L. japonica and expansion of medicinal resources.

A metagenomic next-generation sequencing (mNGS)-based analysis of bronchoalveolar lavage samples in patients with an acute exacerbation of chronic obstructive pulmonary disease.

The role of the bronchoalveolar lavage fluid (BALF) microbiome in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) remains unclear. The advent of the metagenomic next-generation sequencing (mNGS) has made it possible to reveal the complex microbiome composition of the respiratory tract. This study aimed to explore whether there are differences in the BALF microbiome of AECOPD patients with different lung functions. We enrolled 55 AECOPD patients and divided them into a mild group (n = 31) and a severe group (n = 24) according to their lung function. We collected BALF and submitted it to mNGS and bioinformatics analysis. At the species level, mNGS identified 264 bacteria, 13 fungi and 12 viruses in the mild group, and 174 bacteria, 6 fungi and 6 viruses in the severe group. Mixed bacterial and viral infection occurred in both groups. At the genus level, Rothia and Veillonella were more abundant in the mild group, while Pseudomonas and Staphylococcus were more abundant in the severe group. At the species level, compared with the mild group, the relative abundance of Haemophilus influenzae and Pseudomonas aeruginosa was increased in the severe group. Besides, the BALF microbiome composition was similar between the two groups, and there was no significant difference in α and ß diversity. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) (%) showed no significant correlation with the Shannon or Simpson index. The microbiome abundance was different between the mild and severe groups; however, microbiome diversity was similar between the two groups. Based on our findings, Haemophilus influenzae and Pseudomonas aeruginosa may be the pathogenic bacteria that cause the difference in lung function in patients with AECOPD.

Evaluation of acetic acid treatment of fresh-cut water chestnuts using gray-correlation analysis based on the variation-coefficient weight.

Introduction: The demand for fresh-cut water chestnuts, a convenient and nutritive vegetable, is increasing in market. However, the slicing of water chestnuts can cause mechanical damage to tissue, which results in quality deterioration. We aimed to select the optimal treatment through a comprehensive comparison of the preservation effect of acetic acid, which could prolong the shelf life of fresh-cut water chestnuts and improve their storage quality. Methods: A comprehensive evaluation was conducted using the gray-correlation method based on the variation-coefficient weight to observe the treatment of 0, 2 and 5% acetic acid. Their effects on color, weight loss rate, and the content of ascorbic acid, total sugar, reducing sugar, soluble protein, and free amino acid were determined. Results: The color, weight loss rate, and nutritional content of fresh-cut chestnuts varied under different processing and storage times. When stored for more than 4 days, the b* value, and the content of total sugar and soluble protein in CK were higher than those in 2% or 5% acetic acid, but the weight loss rate, and the content of ascorbic acid and free amino acid in CK were less than those in acetic acid treatments. Considering various indicators, it was difficult to determine which treatment to choose for fresh-cut water chestnut preservation. The gray-correlation analysis results indicated that when stored for 8, 12, or 16 days, the gray-correlation degree of 5% acetic acid was the highest, while that of the control was the lowest. It could be directly concluded by the gray-correlation degree that when the storage time exceeded 4 days, acetic acid could be used to improve storage quality, and 5% acetic acid had a better preservation effect than 2%. Fresh-cut water chestnuts can be stored for 4 days without the need for acetic acid treatment. Conclusion: These findings could provide information and comprehensive evaluation methods for the preservation of fresh-cut fruits and vegetables. The next step is to evaluate the preservation effect of acetic acid by measuring its effects on other indicators of fresh-cut water chestnuts (e.g., flavonoids, and microorganisms), providing ideas for the research of preservatives.

Influence of entropy on catalytic performance of high-entropy oxides (NiMgZnCuCoOx) in peroxymonosulfate-mediated acetaminophen degradation.

Developing a high-performance activator is crucial for the practical application of peroxymonosulfate-based advanced oxidation processes (PMS-AOPs). High-entropy oxides (HEOs) have attracted increasing attention due to their stable crystal structure, flexible composition and unique functionality. However, research into the mechanisms by which HEOs function as PMS activators for degrading organic pollutants remains insufficient, and the relationship between entropy and the catalytic performance of HEOs has yet to be clarified. In this study, we synthesized NiMgZnCuCoOx with different levels of entropy as PMS activators for acetaminophen (APAP) degradation, and observed a significant effect for entropy on the catalytic performance. Sulfate radicals (SO4•‒) were identified as the primary reactive oxygen species (ROS), while hydroxyl radicals (•OH) and singlet oxygen (1O2) act as secondary ROS during APAP degradation. Both the Co2+ contents and the oxygen vacancy concentration in NiMgZnCuCoOx are found to increase with the entropy. An increase in the Co2+ sites leads to more activation sites for PMS activation, while excessive oxygen vacancies consume PMS, producing weak oxidation species, and affect the electron-donating ability of Co2+. Consequently, the NiMgZnCuCoOx with middle level of entropy exhibits the optimal performance with APAP degradation rate and mineralization rate reaching 100% and 74.22%, respectively. Furthermore, the degradation intermediates and their toxicities were assessed through liquid chromatography-mass spectrometry and quantitative structure-activity relationship analysis. This work is expected to provide critical insight into the impact of the HEOs entropy on the PMS activation and guide the rational design of highly efficient peroxymonosulfate activators for environmental applications.

Revealing the material basis and mechanism for the inhibition of intestinal peristalsis by Zingiber officinale Roscoe through integrated metabolomics, serum pharmacochemistry, and network pharmacology.

Abnormal relaxation and contraction of intestinal smooth muscle can cause various intestinal diseases. Diarrhea is a common and important public health problem worldwide in epidemiology. Zingiber officinale Roscoe (fresh ginger) has been found to treat diarrhea, but the material basis and mechanism of action that inhibits intestinal peristalsis remain unclear. Metabolomics and serum pharmacology were used to identify differential metabolites, metabolic pathways, and pharmacodynamic substances, and were then combined with network pharmacology to explore the potential targets of ginger that inhibit intestinal peristalsis during diarrhea treatment, and the targets identified were verified using molecular docking and molecular dynamic simulation. We found that 25 active components of ginger (the six most relevant components), 35 potential key targets (three core targets), 40 differential metabolites (four key metabolites), and four major metabolic pathways were involved in the process by which ginger inhibits intestinal peristalsis during diarrhea treatment. This study reveals the complex mechanism of action and pharmacodynamic material basis of ginger in the inhibition of intestinal peristalsis, and this information helps in the development of new Chinese medicine to treat diarrhea and lays the foundation for the clinical application of ginger.

First Report of Leaf Spot Disease on Lonicera japonica Caused by Nigrospora oryzae in China.

Lonicera japonica Thunb. is a traditional Chinese medicinal plant, which widely cultivated in China, Japan and Korea. From August to October in 2021 and 2022, severe leaf spots symptoms were observed on L. japonica in medicinal botanical garden of Shandong University of Traditional Chinese Medicine (36°55'89"N, 116°79'91"E), Jinan, Shandong Province, China. The disease incidence was above 80% in the 25 acre cultivation area. Early symptoms were small brown spots on the leaves. Then the number of small spots gradually increased and spread over the entire leaves. The small brown spots seldom merge together to form larger lesions. Leaves with typical symptoms were collected from twenty individual plants, and cut into small 5×5 mm fragments in the junction of infected and healthy tissues. The fragments were sterilized in 75% ethanol for 30 s and 1% NaClO for 60 s, rinsed three times in sterile water, and then placed on potato dextrose agar (PDA). After 3 days of incubation at 25°C, fungal plugs along the edge of the colony were cut and transferred to new PDA for purification. A total number of 23 colonies with similar morphological characteristics were obtained, and three representative strains (Lj14, Lj18 and Lj20) were selected for subsequent study. The colonies grew rapidly on PDA and covered the entire petri dish in 4 days. Colonies had abundant aerial hyphae, initially white, round, later turning gray and black. Conidia were oblate or nearly spherical, single-celled, black, and measured in size from 9.6 to 13.2 µm × 7.9 to 16.1 µm in diameter (n=150) (Figure S1). The observed characteristics were close to those of Nigrospora spp. ( Wang et al. 2017). The genomic DNA was extracted, and PCR amplification of the rDNA internal transcribed spacer (ITS), ß-tubulin gene (TUB), and translation elongation factor 1-alpha gene (TEF1) were completed by primers ITS1/ITS4, Bt2a/Bt2b and EF1-728F/EF1-986R (Carbone and Kohn, 1999). Sequences were deposited in GenBank (accession nos. OR936661, OR936662, OR936671 for ITS, OR947626, OR947627, OR947628 for TUB, and OR947629, OR947630, OR947631 for TEF1 sequences, respectively). BLAST analyses of ITS (OR936661), TUB(OR947626) and TEF1 (OR947629) sequences exhibited 100% (487 bp out of 487 bp), 99.48% (380 bp out of 382 bp), and 99.6% (248 bp out of 249 bp) similarity to the sequences of N. oryzae strains KoLRI_053384 (MZ855426), LC2991 (KY019496) and LC7307 (KY019409), respectively. Lj14, Lj18 and Lj20 formed a clade with N. oryzae LC6763 and LC2991 in phylogenetic tree (Figure S2). Based on morphological and molecular evidence, the pathogen was identified as N. oryzae (Berk. &Broome) Petch. To fulfill Koch's postulates, the pathogenicity was tested in vivo experiments. Thirty non-wounded healthy leaves of ten intact plants were inoculated with 10 µl spore suspension (106 spores/ml) of three strains, respectively. As negative control, thirty leaves of ten healthy plants were inoculated with sterile water. The inoculated plants were placed at 28°C in the growth chamber with high relative humidity. The pathogenicity tests were repeated three times. Distinct symptoms similar to that of natural conditions were observed on the leaves of inoculated plants after 4 to 7 days. The strain was reisolated from the lesions and identified as N. oryzae by morphological features and ITS sequence. The pathogen has been reported to cause leaf spot disease on tobacco (Wang et al. 2022) and asiatic dayflower (Qiu et al. 2022). To our knowledge, this is the first report of leaf spot caused by N. oryzae on Lonicera japonica in China. The research will be helpful for leaf spot disease control.

The fertility research of "Huajin 6", a new variety of honeysuckle.

The aim of this study was to investigate the fertility of "Huajin 6" and the effect of exogenous methyl jasmonate on its fertility. In this study, "Huajin 6", "Huajin 6" treated with methyl jasmonate and "Damaohua" were used as the research objects, the stamen phenotypes and the shape of pollen grains were observed, pollen viability and stigma receptivity were measured. The results showed that the pistil structure and function were normal, and although the stamen anthers did not dehisce, they were still capable of producing pollen with a certain amount of vigor. Methyl jasmonate could promote the opening of the flowers of "Huajin 6" and improve the development of pollen grains to a certain extent, but it could not promote anthers dehiscence of "Huajin 6". This study can provide theoretical guidance for the cultivation of new honeysuckle varieties using "Huajin 6".

Modified Hongteng Baijiang decoction enema improves sequelae of pelvic inflammatory disease by regulating the LIF/JAK2/STAT3 pathway and gut microbiota.

OBJECTIVE: The sequelae of pelvic inflammatory disease (SPID) are major causes of secondary infertility. Modified Hongteng Baijiang decoction (MHTBD) has produced positive results in the treatment of patients with chronic pelvic inflammatory disease; however, its role in SPID remains elusive. Therefore, this study clarified the role of MHTBD in SPID pathogenesis. METHODS: The main components in MHTBD were analyzed by using liquid chromatography‒mass spectrometry (LC/MS). An SPID rat model was established, and the rats were treated with different doses of MHTBD (0.504 g of raw drug/kg, 1.008 g of raw drug/kg, and 2.016 g of raw drug/kg). Endometrial pinopodes were observed via scanning electron microscopy, endometrial thickness and inflammatory cell infiltration were assessed via HE staining, and the expression of estrogen receptor (ER), progesterone receptor (PR), integrin ß3 (ITGB3), and CD31 in the endometrium was detected by using immunohistochemistry. Western blot analysis was used to detect the protein expression of LIF, JAK2, p-JAK2, STAT3, and p-STAT3 in the endometrium. Moreover, the changes in the gut microbiota were analyzed via 16S rRNA sequencing. RESULTS: MHTBD improved endometrial receptivity, attenuated endometrial pathologic damage, reduced inflammatory cell infiltration, decreased ER and PR expression in the endometrium, and promoted the expression of LIF, p-JAK2, and p-STAT3 in the endometrium (p < .05) in SPID rats. Additionally, MHTBD treatment affected the composition of the gut microbiota in SPID rats. Furthermore, MHTBD attenuated endometrial receptivity and pathological damage in SPID rats by promoting the LIF/JAK2/STAT3 pathway. CONCLUSION: MHTBD attenuates SPID in rats by promoting the LIF/JAK2/STAT3 pathway and improving the composition of the gut microbiota. MHTBD may be a valuable drug for SPID therapy.

CT-Net: an interpretable CNN-Transformer fusion network for fNIRS classification.

Functional near-infrared spectroscopy (fNIRS), an optical neuroimaging technique, has been widely used in the field of brain activity recognition and brain-computer interface. Existing works have proposed deep learning-based algorithms for the fNIRS classification problem. In this paper, a novel approach based on convolutional neural network and Transformer, named CT-Net, is established to guide the deep modeling for the classification of mental arithmetic (MA) tasks. We explore the effect of data representations, and design a temporal-level combination of two raw chromophore signals to improve the data utilization and enrich the feature learning of the model. We evaluate our model on two open-access datasets and achieve the classification accuracy of 98.05% and 77.61%, respectively. Moreover, we explain our model by the gradient-weighted class activation mapping, which presents a high consistent between the contributing value of features learned by the model and the mapping of brain activity in the MA task. The results suggest the feasibility and interpretability of CT-Net for decoding MA tasks.

The protective effect of Lonicera japonica Thunb. against lipopolysaccharide-induced acute lung injury in mice: Modulation of inflammation, oxidative stress, and ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Various components of Lonicera japonica Thunb. (LJT) exhibit pharmacological activities, including anti-inflammatory and antioxidant effects. Nevertheless, the relationship between LJT and ferroptosis remains largely unexplored. AIM OF THE STUDY: The purpose of this research was to look into the role of LJT in regulating LPS-induced ferroptosis in ALI and to compare the effects of different parts of LJT. MATERIALS AND METHODS: We established a mice ALI model by treating with LPS. Administered mice with different doses of Lonicerae Japonicae Flos (LJF), Lonicera Japonica Leaves (LJL) and Lonicerae Caulis (LRC) extracts, respectively. The levels of IL-6, IL-1ß, TNF-α, IL-4, IL-10, and PGE2 in bronchoalveolar lavage fluid (BALF) were measured using enzyme-linked immunosorbent assay. Furthermore, the concentrations of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), and total ferrous ions (Fe2+) in lung tissues were evaluated. Hematoxylin and eosin staining was conducted to examine the morphological structure of lung tissues. Transmission electron microscopy was used to investigate the ultrastructural morphology of mitochondria. Furthermore, the effects of LJT were evaluated via immunohistochemical staining, western blotting, and quantitative real-time polymerase chain reaction analyses. Finally, employing molecular docking and molecular dynamics research techniques, we aimed to identify crucial components in LJT that might inhibit ferroptosis by targeting nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4). RESULTS: We observed that pretreatment with LJT significantly mitigated LPS-induced lung injury and suppressed ferroptosis. This was supported by reduced accumulation of pro-inflammatory cytokines, ROS, MDA, and Fe2+, along with increased levels of anti-inflammatory cytokines, SOD, GSH, Nrf2, and GPX4 in the lung tissues of ALI mice. Luteolin-7-O-rutinoside, apigenin-7-O-rutinoside, and amentoflavone in LJT exhibit excellent docking effects with key targets of ferroptosis, Nrf2 and GPX4. CONCLUSIONS: Pretreatment with LJT may alleviate LPS-induced ALI, possibly by suppressing ferroptosis. Our initial results indicate that LJT activates the Nrf2/GPX4 axis, providing protection against ferroptosis in ALI. This finding offers a promising therapeutic candidate for ALI treatment.

Transcriptome sequencing and metabolome analysis reveal the molecular mechanism of Salvia miltiorrhiza in response to drought stress.

Salvia miltiorrhiza is commonly used as a Chinese herbal medicine to treat different cardiovascular and cerebrovascular illnesses due to its active ingredients. Environmental conditions, especially drought stress, can affect the yield and quality of S. miltiorrhiza. However, moderate drought stress could improve the quality of S. miltiorrhiza without significantly reducing the yield, and the mechanism of this initial drought resistance is still unclear. In our study, transcriptome and metabolome analyses of S. miltiorrhiza under different drought treatment groups (CK, A, B, and C groups) were conducted to reveal the basis for its drought tolerance. We discovered that the leaves of S. miltiorrhiza under different drought treatment groups had no obvious shrinkage, and the malondialdehyde (MDA) contents as well as superoxide dismutase (SOD) and peroxidase (POD) activities dramatically increased, indicating that our drought treatment methods were moderate, and the leaves of S. miltiorrhiza began to initiate drought resistance. The morphology of root tissue had no significant change under different drought treatment groups, and the contents of four tanshinones significantly enhanced. In all, 5213, 6611, and 5241 differentially expressed genes (DEGs) were shared in the A, B, and C groups compared with the CK group, respectively. The results of KEGG and co-expression analysis showed that the DEGs involved in plant-pathogen interactions, the MAPK signaling pathway, phenylpropanoid biosynthesis, flavonoid biosynthesis, and plant hormone signal transduction responded to drought stress and were strongly correlated with tanshinone biosynthesis. Furthermore, the results of metabolism analysis indicated that 67, 72, and 92 differentially accumulated metabolites (DAMs), including fumarate, ferulic acid, xanthohumol, and phytocassanes, which were primarily involved in phenylpropanoid biosynthesis, flavonoid biosynthesis, and diterpenoid biosynthesis pathways, were detected in these groups. These discoveries provide valuable information on the molecular mechanisms by which S. miltiorrhiza responds to drought stress and will facilitate the development of drought-resistant and high-quality S. miltiorrhiza production.

Assessing parameter efficient methods for pre-trained language model in annotating scRNA-seq data.

Annotating cell types of single-cell RNA sequencing (scRNA-seq) data is crucial for studying cellular heterogeneity in the tumor microenvironment. Recently, large-scale pre-trained language models (PLMs) have achieved significant progress in cell-type annotation of scRNA-seq data. This approach effectively addresses previous methods' shortcomings in performance and generalization. However, fine-tuning PLMs for different downstream tasks demands considerable computational resources, rendering it impractical. Hence, a new research branch introduces parameter-efficient fine-tuning (PEFT). This involves optimizing a few parameters while leaving the majority unchanged, leading to substantial reductions in computational expenses. Here, we utilize scBERT, a large-scale pre-trained model, to explore the capabilities of three PEFT methods in scRNA-seq cell type annotation. Extensive benchmark studies across several datasets demonstrate the superior applicability of PEFT methods. Furthermore, downstream analysis using models obtained through PEFT showcases their utility in novel cell type discovery and model interpretability for potential marker genes. Our findings underscore the considerable potential of PEFT in PLM-based cell type annotation, presenting novel perspectives for the analysis of scRNA-seq data.

Expectant management for umbilical artery thrombosis in the third trimester of pregnancy: a case report.

Background: Umbilical artery thrombosis (UAT) is a rare complication of pregnancy and is associated with adverse pregnancy outcomes, including fetal intrauterine distress, intrauterine growth restriction, and still birth. UAT is unpredictable, and prenatal diagnosis is challenging. There is no consensus on the treatment strategy of UAT, especially for patients with prenatal detection of one of the umbilical artery embolisms. In most previous cases, an emergency cesarean section was performed, or intrauterine fetal death occurred at the time of UAT diagnosis. Case presentation: In this report, we describe a case of thrombosis in one of the umbilical arteries detected by routine ultrasonography at 31+3 weeks of gestation in a 34-year-old woman. Following expectant management with intensive monitoring for 4 four days, an emergency cesarean section was performed because of abnormal fetal umbilical cord blood flow and middle cerebral artery blood flow; the newborn was in good condition at birth. The final umbilical cord histopathology revealed thrombosis in one of the umbilical arteries. Both mother and newborn described in this case underwent long-term follow-up for nearly 2 two years and are currently in good health without any complications. Conclusions: Based on our experience, obstetricians should comprehensively consider the current gestational age and fetal intrauterine status when UAT is suspected to determine the best delivery time. The appropriate gestational age should be prolonged as long as the mother and fetus are stable when the fetus is immature, trying our best to complete the corticosteroid treatment to promote fetal lung maturity and magnesium sulfate to protect fetal brain. During expectant management, ultrasound monitoring, electronic fetal heart monitoring, and fetal movement counting should be strengthened. Clinicians should ensure that the patients and their families are informed about all potential risks of expectant management for UAT.