A new loach species of the genus Oreonectes (Teleostei, Cypriniformes, Nemacheilidae) from Guangxi, China.

A new loach species, Oreonectesandongensissp. nov. is described from the Guangxi Zhuang Autonomous Region, China. The new species can be differentiated from other members of the genus by combinations of characters: a developed posterior chamber of the swim bladder, 13-14 branched caudal-fin rays, 8-16 lateral-line pores, body width 12-15% of standard length (SL), interorbital width 42-47% of head length (HL), and caudal peduncle length 11-16% of SL. Bayesian inference phylogenetic analysis based on mitochondrial Cyt b provided strong support for validity of O.andongensissp. nov. (uncorrected p-distance 6.0-7.5%).

Targeting the organelle for radiosensitization in cancer radiotherapy.

Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.

A New Species of the Blind Cave Loach Genus Protocobitis (Cypriniformes: Cobitidae), Protocobitis longicostatus sp. nov., from Guangxi, China.

Protocobitis species are typical cave-dwelling fish, exhibiting distinctive morphological adaptations such as colorless body, lack of eyes, and reduced scales and ribs in response to their extreme cave habitats. Distinct from the recorded species, P. anteroventris, P. polylepis, and P. typhlops, a new species, Protocobitis longicostatus sp. nov., is described from Guangxi Zhuang Autonomous Region, China. Protocobitis longicostatus sp. nov. can easily be distinguished from all known congeners by the following characteristics: whole body covered by scales except head, 12 branched caudal fin rays, and long ribs. These species face threats from habitat degradation, hydrological changes, and environmental pollution. Thus, the conservation of cavefish in China has become an urgent issue.

The Machine Learning Model for Predicting Inadequate Bowel Preparation before Colonoscopy: a Multicenter Prospective Study.

BACKGROUND AND AIMS: Colonoscopy is a critical diagnostic tool for colorectal diseases; however, its effectiveness depends on adequate bowel preparation (BP). This study aimed to develop a machine learning predictive model based on Chinese adults for inadequate BP . METHODS: A multicenter, prospective study was conducted on adult outpatients undergoing colonoscopy from January 2021 to May 2023. Data on patient characteristics, comorbidities, medication use, and BP quality were collected. Logistic regression and four machine learning models (support vector machines, decision trees, extreme gradient boosting, and bidirectional projection network) were used to identify risk factors and predict inadequate BP. RESULTS: Of 3217 patients, 21.14% had inadequate BP. The decision trees model demonstrated the best predictive capacity with an area under the receiver operating characteristic curve of 0.80 in the validation cohort. The risk factors at the nodes included body mass index, education grade, use of simethicone, diabetes, age, history of inadequate BP, and longer interval. CONCLUSION: The decision trees model we created and the identified risk factors can be used to identify patients at higher risk for inadequate BP before colonoscopy, for whom more PEG or auxiliary medication should be used.

Size-resolved distribution of trace elements in lysimeter soil solutions under contrasting long-term agricultural management to assess their bioavailability.

The chemical species of trace elements (TEs) in agricultural soils is highly variable under diverse conditions, requiring tools with clear resolution and minimal disturbance for exploration. A novel surgical (316L) stainless steel (SS) lysimeter with a 5 µm pore size was developed to collect field soil solutions. The size-resolved distribution of TEs were characterized into total (nitric acid digestion), particulate (0.45-5 µm), dissolved (<0.45 µm), colloidal (1 kDa to 0.45 µm), and mainly ionic (<1 kDa) fractions in the lysimeter soil solutions. Total concentrations of TEs (dry weight basis) in acid digested Gray Luvisolic soils were analyzed. Most TEs in lysimeter soil solutions were present in particulate phases, relevant to their geochemical affinities and occurrences in soil minerals. Among dissolved fractions, As, Ba, Co, Li, Mn, Tl, and V existed as mainly ionic species in the soil solutions. Copper, Pb, Al, Th, and U showed variable associations with dissolved organic matter (DOM) and/or inorganic colloids among agricultural treatments. Inorganic NPKS or NKS fertilizer applications with lower pH (5.25-5.74) enhanced mobility and potential bioavailability of Ba, Co, Li, Mn, and Pb present in mainly ionic species, compared with other locations (pH 5.82-6.37). Manure application exhibited a dual effect, potentially increasing bioavailability for As, Tl, and V due to probably enhanced cation exchange capacity (CEC), while also facilitating specific adsorption of Cu and U on DOM, potentially reducing their bioavailability depending on DOM molecular weight. Colloidal and ionic Al and Th concentrations were higher in forest soils than agricultural soils, with extremely low potential bioavailability of Th attributed to strong precipitation with inorganic colloids and adsorption on DOM. The lysimeter sampling and size fractionation method provided a clear insight into agricultural effects on TE distributions and enhancing understanding of agricultural soil health in terms of TE bioavailability in situ.

Immunoglobulin A Vasculitis With Intussusception in Children.

BACKGROUND: Immunoglobulin A (IgA) vasculitis with intussusception is acute and severe vasculitis combined with acute abdomen in children. The diagnosis of the disease depends on the results of imaging examinations, and its treatment mainly includes enema and surgery. The literature summarized the detailed diagnosis and treatment data in previous literature reports. METHODS: We described the clinical manifestations, ultrasonic features, and treatment of patients admitted to a single center and reviewed previous literature regarding cases with detailed clinical data in the PubMed database within the past 20 years. RESULTS: The review included 36 patients, including 22 boys and 14 girls. A total of 32 patients were diagnosed using ultrasound (88.9%). The main sites of intussusception were the ileum and ileocolon in 16 (44.4%) and 11 (30.6%) cases, respectively. Thirteen patients (36.1%) were treated with enema, with 6 responding to the treatment. 26 patients (72.2%) underwent surgical treatment. Patients with ileal intussusception were more likely to be treated with surgery than those with colonic intussusception (P < .05). The single-center clinical data of 23 patients showed that there was no significant difference in laboratory test findings between patients with and without surgical treatment (P > .05). Patients with long insertion lengths were more likely to require surgery and resection (P < .05). CONCLUSIONS: Ultrasonography is the first-line investigation for diagnosis. The main sites of intussusception were ileum and ileocolon. The length of intubation was related to surgery; treatment is according to the intussusception site. Air enema is not suitable for intussusception of the small intestine.

Cancer cell membrane-coated bacterial ghosts for highly efficient paclitaxel delivery against metastatic lung cancer.

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4+/CD8a+ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.

Integration of lipidomics and metabolomics reveals plasma and urinary profiles associated with pediatric Mycoplasma pneumoniae infections and its severity.

Mycoplasma pneumoniae is a significant contributor to lower respiratory infections in children. However, the lipidomics and metabolics bases of childhood M. pneumoniae infections remain unclear. In this study, lipidomics and metabolomics analyses were conducted using UHPLC-LTQ-Orbitrap XL mass spectrometry and gas chromatography-triple quadrupole mass spectrometry on plasma (n = 65) and urine (n = 65) samples. MS-DIAL software, in combination with LipidBlast and Fiehn BinBase DB, identified 163 lipids and 104 metabolites in plasma samples, as well as 208 metabolites in urine samples. Perturbed lipid species (adjusted p < 0.05) were observed, including lysophosphatidylethanolamines, phosphatidylinositols, phosphatidylcholines, phosphatidylethanol amines, and triglycerides. Additionally, differential metabolites (adjusted p < 0.05) exhibited associations with amino acid metabolism, nucleotide metabolism, and energy metabolism. Thirteen plasma metabolites, namely l-hydroxyproline, 3-phosphoglycerate, citric acid, creatine, inosine, ribitol, α tocopherol, cholesterol, cystine, serine, uric acid, tagatose, and glycine, showed significant associations with disease severity (p < 0.05) and exhibited distinct separation patterns in M. pneumoniae-infected bronchitis and pneumonia, with an area under the curve of 0.927. Nine of them exhibited either positive or negative correlations with neutrophil or lymphocyte percentages. These findings indicated significant systemic metabolic shifts in childhood M. pneumoniae infections, offering valuable insights into the associated metabolic alterations and their relationship with disease severity.

The effects of Lactobacillus reuteri microcapsules on radiation-induced brain injury by regulating the gut microenvironment.

A radiation-induced brain injury (RIBI) is a major adverse event following radiotherapy of malignant tumors. RIBI would affect cognitive function, leading to a series of complications and even death. However, the pathogenesis of RIBI is still unclear, and it still lacks specific therapeutic drugs. The gut-brain bidirectional communication may be mediated by various microbiota and metabolites in the gastrointestinal tract. Probiotics are closely related to physiological health. The theory of the gut-brain axis provides us with a new idea to improve the gut microenvironment by supplementing probiotics against RIBI. Here, Lactobacillus reuteri microcapsules (LMCs) were prepared, which were predominantly irregular spheres with a rough surface under a scanning electron microscope and a narrow size distribution ranging from 20 to 700 µm. The transmission electron microscopy images showed that the structure of microcapsules containing Lactobacillus reuteri (L. reuteri) was a core and shell structure. The survival of L. reuteri in microcapsules was significantly more than that of free L. reuteri in the simulated stomach environment of pH 1.2. 16S rDNA sequencing showed that LMCs observably increased the relative abundance of Lactobacillus in RIBI mice. More importantly, compared with the RIBI model mice, the behavior of RIBI mice treated with LMCs was significantly improved. In addition, LMCs greatly alleviated the pathological damage of the hippocampus and intestines in the mice after irradiation and reduced the level of TNF-α and IL-6 in vivo. Generally, LMCs are a promising oral preparation, which provide new ideas and methods for the treatment of RIBI.

Description of a New Species of Hua (Gastropoda: Semisulcospiridae) from Guizhou, China, Based on Morphology and Molecular Evidence.

A new species of Hua, Hua qiannanensis sp. nov., is described from Guizhou Province, China, based on morphological and molecular evidence. The new species can be distinguished from its congeners by the following combination of characters: the smooth shell, only three smaller cusps of lateral teeth on the inner side, outer marginal teeth with eight flattened and rounded denticles, an ovipositor pore in females, and BW/H ≥ 80%, B/H = 76.8-82.3%. Molecular analysis based on partial mitochondrial COI and 16S rDNA also supports the systematic position of the new taxon.

Biogeographic Origin of Kurixalus (Anura, Rhacophoridae) on the East Asian Islands and Tempo of Diversification within Kurixalus.

The ancestral area of Kurixalus on the East Asian islands is under dispute, and two hypotheses exist, namely that distribution occurred only on the Asian mainland (scenario of dispersal) and that wide distribution occurred on both the Asian mainland and the East Asian islands (scenario of vicariance). In this study, we conducted biogeographic analyses and estimated the lineage divergence times based on the most complete sampling of species, to achieve a more comprehensive understanding on the origin of Kurixalus on the East Asian islands. Our results revealed that the process of jump dispersal (founder-event speciation) is the crucial process, resulting in the distribution of Kurixalus on the East Asian islands, and supported the model of the Asian mainland origin: that Kurixalus on the East Asian islands originated from the Asian mainland through two long-distance colonization events (jump dispersal), via the model of vicariance of a widespread ancestor on both the Asian mainland and the East Asian islands. Our results indicated that choices of historical biogeography models can have large impacts on biogeographic inference, and the procedure of model selection is very important in biogeographic analysis. The diversification rate of Kurixaus has slightly decreased over time, although the constant-rate model cannot be rejected.

Induction of heme oxygenase-1 antagonizes PM2.5-induced pulmonary VEGFA expression through regulating HIF-1α.

Particulate matter (PM) 2.5 has long been regarded as a major risk factor of the respiratory system, which constitutes a threat to human health. Although the positive relationship between PM2.5 exposure and the development of respiratory diseases has been well established, limited studies investigate the intrinsic self-protection mechanisms against PM2.5-induced respiratory injuries. Excessive pulmonary inflammation served as a key pathogenic mechanism in PM2.5-induced airway dysfunction, and we have previously shown that PM2.5 induced the production of vascular endothelial growth factor A (VEGFA) in the bronchial epithelial cells, which subsequently led to pulmonary inflammatory responses. In the current study, we found that PM2.5 also concurrently induced the expression of the stress-responsive protein heme oxygenase-1 (HO-1) along with VEGFA in the bronchial epithelial cells both in vivo and in vitro. Importantly, knocking down of HO-1 expression significantly increased the synthesis and secretion of VEGFA; while overexpression of HO-1 showed the opposite effects, indicating that HO-1 induction can antagonize VEGFA production in the bronchial epithelial cells upon PM2.5 exposure. Mechanistically, HO-1 inhibited PM2.5-evoked VEGFA induction through modulating hypoxia-inducible factor 1 alpha (HIF-1α), which was the upstream transcriptional factor of VEGFA. More specifically, HO-1 could not only inhibit HIF-1α expression, but also suppress its transactivity. Taken together, our results suggested that HO-1 was an intrinsic protective factor against PM2.5-induced pulmonary VEGFA production with a mechanism relating to HIF-1α, thus providing a potential treatment strategy against PM2.5 triggered airway injuries.

Urine metabolites and viral pneumonia among children: a case-control study in China.

Background: Viral pneumonia in children is common and has grave consequences. The study aims to better understand the pathophysiological processes involved in the onset and progression of viral pneumonia and identify common effects or biomarkers across different viruses. Methods: This study collected urine samples from 96 patients with viral pneumonia including respiratory syncytial virus (RSV) (n=30), influenza virus (IV) (n=23), parainfluenza virus (PIV) (n=24), and adenovirus (ADV) (n=19), and 31 age- and sex-matched normal control (NC) subjects. The samples were analyzed using liquid chromatography coupled with mass spectrometry (LC-MS) to identify endogenous substances. The XCMS Online platform was utilized for data processing and analysis , including feature detection, retention time correction, alignment, annotation, and statistical analysis for difference between groups and biomarker identification. Results: A total of 948 typical metabolites were identified using the XCMS Online platform with the Mummichog technique. After analyzing the data, 24 metabolites were selected as potential biomarkers for viral pneumonia, of which 16 were aspartate and asparagine metabolites, byproducts of alanine, leucine, and isoleucine degradation, and butanoate metabolites. Conclusions: This study specific metabolites and altered pathways in children with viral pneumonia and propose that these findings could contribute to the discovery of new treatments and the development of antiviral drugs.

Mesalazine hollow suppositories based on 3D printing for treatment of ulcerative colitis.

Mesalazine (MSZ) suppositories are a first-line medication for the localized treatment of ulcerative colitis (UC). However, the frequent defecation of patients with UC influences the retention of the suppository in the rectum and multiple doses have to be applied. Here, a mesalazine hollow suppository (MHS) is developed using three-dimensional (3D) printing. The MHS is composed of an inner supporting spring and an outer MSZ-loaded curved hollow shell. Springs were prepared using fused deposition modeling (FDM) 3D printing with thermoplastic urethane filaments, followed by splitting. The optimal parameters, including elasticity, filament diameter, spring inner diameter, and filament distance, were screened. The shell was prepared by FDM 3D printing utilizing MSZ, polyvinyl alcohol, and polyethylene glycol, which were assembled with springs to obtain FDM 3D-printed MHS (F-MHS); if 3D-printed metal molding was used in preparing shell, mold-formed MHS (M-MHS) was obtained. The F-MHS exhibited faster MSZ release than the M-MHS; therefore, the molding method is preferable. The inserted M-MHS was retained in the rat rectum for 5 h without affecting defecation. M-MHS alleviated tissue damage of UC rats and reduced inflammation with low levels of myeloperoxidase and proinflammatory cytokines. Personalized MHS is a promising medication for the localized treatment of UC.

A new species of cascade frog (Anura: Ranidae: Amolops) from central Yunnan, China.

A new species of the genus Amolops, Amolops ailao sp. nov., is described from central Yunnan, China. The new species belongs to the A. mantzorum species group. Phylogenetic analyses based on the combination of mitochondrial 16S rRNA, COI, and cytb genes revealed that the new species is the sister taxon to Amolops ottorum with strong support. Genetically, the new species differs from A. ottorum by 5.0% in cytb sequences. Morphologically, the new species can be distinguished from known congeners by the combination of the following characters: true dorsolateral folds absent, but dorsolateral folds formed by series of glands present; circummarginal groove on tip of first finger absent; body size small (males SVL 33.0-35.1 mm and female SVL 41.3 mm); HW/SVL 0.32‒0.35; UEW/SVL 0.08‒0.10; THL/SVL 0.52‒0.56; vomerine teeth absent; interorbital distance narrower than internarial distance; tympanum distinct, less than half eye diameter; supratympanic fold present, indistinct; a pair of large tubercles on sides of cloaca; tibiotarsal articulation reaching beyond anterior corner of eye; and vocal sac absent. The cladogenesis events within the A. mantzorum group rapidly occurred from Pliocene 4.23 Mya to Pleistocene 1.2 Mya, coinciding with the recent intensive uplift of the Qinghai-Tibetan Plateau since the Pliocene. Combining findings in this study with the most recent taxonomic progress, we consider that there are 20 known Amolops species in Yunnan, China, accounting for the highest proportion of amphibian diversity of Yunnan, and five of them belong to the A. mantzorum group. Among different subfauna and water systems in Yunnan, the species diversity of Amolops in northwestern Yunnan and Nu River Basin is highest.

Application of low-intensity ultrasound by opening blood-brain barrier for enhanced brain-targeted drug delivery.

Brain-targeted drug delivery has been a research hotspot, and substantial amount of related studies were already translated into standard therapy and put into clinical use. However, low effective rate retains a huge challenge for brain disease. Because, the blood-brain barrier (BBB) protects brain from pathogenic molecules and tightly controls the process of molecular transportation, which gives rise to poor-liposoluble drugs or molecules with high molecular weight cannot permeate the barrier to exert treating effect. There is an ongoing process to dig out more methods for efficient brain-targeted drug delivery. Besides modified chemical methods such as prodrugs design and brain-targeted nanotechnology, physical methods as a novel initiative could enhance the treatment effect for brain disease. In our study, the influence of low-intensity ultrasound on transient opening BBB and the related applications were explored. A medical ultrasound therapeutic device (1 MHz) was used on heads of mice at different intensities and for different treating time. Evans blue was used as a model to exhibit the permeability of the BBB after subcutaneous injection. Three types of intensities (0.6, 0.8, and 1.0 W/cm2) and duration times (1, 3, and 5 min) of ultrasound were respectively investigated. It was found that the combinations of 0.6 W/cm2/1 min, 0.6 W/cm2/3 min, 0.6 W/cm2/5 min, 0.8 W/cm2/1 min, and 1.0 W/cm2/1 min could open the BBB sufficiently with significant Evans blue staining in the brain. Brain pathological analysis showed structural change on moderate degree was found on cerebral cortex after ultrasound and could recovered rapidly. There are no obvious changes in the behavior of mice after ultrasound processing. More importantly, the BBB recovered quickly at 12 h after ultrasound application with complete BBB structure and unbroken tight junction, suggesting that ultrasound was safe to apply for brain-targeted drug delivery. Proper use of local ultrasound on the brain is a promising technique to open the BBB and enhance brain-targeted delivery.

Injectable multifunctional chitosan/dextran-based hydrogel accelerates wound healing in combined radiation and burn injury.

Clinical wound management of combined radiation and burn injury (CRBI) remains a huge challenge due to serious injuries induced by redundant reactive oxygen species (ROS), the accompanying hematopoietic, immunologic suppression and stem cell reduction. Herein, the injectable multifunctional Schiff base cross-linked with gallic acid modified chitosan (CSGA)/oxidized dextran (ODex) hydrogels were rationally designed to accelerate wound healing through elimination of ROS in CRBI. CSGA/ODex hydrogels, fabricated by mixing solutions of CSGA and Odex, displayed good self-healing ability, excellent injectability, strong antioxidant activity, and favorable biocompatibility. More importantly, CSGA/ODex hydrogels exhibited excellent antibacterial properties, which is facilitated for wound healing. Furthermore, CSGA/ODex hydrogels significantly suppressed the oxidative damage of L929 cells in an H2O2-induced ROS microenvironment. The recovery of mice with CRBI in mice demonstrated that CSGA/ODex hydrogels significantly reduced the hyperplasia of epithelial cells and the expression of proinflammatory cytokine, and accelerated wound healing which was superior to the treatment with commercial triethanolamine ointment. In conclusion, the CSGA/ODex hydrogels as a wound dressing could accelerate the wound healing and tissue regeneration of CRBI, which provides great potential in clinical treatment of CRBI.

The promising application of hydrogel microneedles in medical application.

OBJECTIVES: Hydrogel microneedles are emerging, and promising microneedles mainly composed of swelling polymers. This review is intended to summarize the preparation materials, formation mechanisms, applications and existing problems of hydrogel microneedles. METHODS: We collected the literature on the materials, preparation and application of hydrogel microneedles in recent years, and summarized their mechanism and application in drugs delivery. KEY FINDINGS: Hydrogel microneedles have higher safety and capabilities of controlled drug release, and have been mainly used in tumour and diabetes treatment, as well as clinical monitoring. In recent years, hydrogel microneedles have shown great potential in drug delivery, and have played the role of whitening, anti-inflammatory and promoting healing. CONCLUSIONS: As an emerging drug delivery idea, hydrogel microneedles for drug delivery has gradually become a research hotspot. This review will provide a systematic vision for the favourable development of hydrogel microneedles and their promising application in medicine, especially drug delivery.

Effects of heating rate and shell colour on the cardiac thermal performance in a polymorphic gastropod Batillaria attramentaria.

Heating rate has gained extensive attention in mechanistic understanding of physiological responses to changing thermal conditions in the context of climate change. In polymorphic gastropods, differences in the absorption of solar energy between dark- and light-coloured individuals lead to supposable differences in their heating rates and body temperatures in sunshine. In the present study, we examined the effect of heating rate on heart rate (HR) in a polymorphic gastropod Batillaria attramentaria. By using biomimetic models, we found that daily maximum temperature of snails with a dark unbanded shell (D-type morph) was higher than snails with a white line on the upper side of each whorl (UL-type morph) by 0.6 °C when exposed to sunlight, but there was no apparent difference in heating rates between D- and UL-type models. We measured HR of snails at various heating rates from 3.0 to 9.0 °C h-1. Faster heating rates significantly increased maximum thermal tolerance in both D- and UL-type snails, highlighting the importance to have thorough knowledge on the heating rate in the field to obtain accurate maximum thermal limit of gastropods. Critical temperature at which HR precipitously declines was higher in D-type snails than UL-type snails. Our results suggested that the impacts of heating rate as well as the shell colour should be considered to gain a mechanistic understanding of the population dynamics of polymorphic gastropods.

Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung Injury.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) induces a severe cytokine storm that may cause acute lung injury/acute respiratory distress syndrome (ALI/ARDS) with high clinical morbidity and mortality in infected individuals. Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid isolated and extracted from Stephania cepharantha Hayata. It exhibits various pharmacological effects, including antioxidant, anti-inflammatory, immunomodulatory, anti-tumor, and antiviral activities. The low oral bioavailability of CEP can be attributed to its poor water solubility. In this study, we utilized the freeze-drying method to prepare dry powder inhalers (DPI) for the treatment of acute lung injury (ALI) in rats via pulmonary administration. According to the powder properties study, the aerodynamic median diameter (Da) of the DPIs was 3.2 µm, and the in vitro lung deposition rate was 30.26; thus, meeting the Chinese Pharmacopoeia standard for pulmonary inhalation administration. We established an ALI rat model by intratracheal injection of hydrochloric acid (1.2 mL/kg, pH = 1.25). At 1 h after the model's establishment, CEP dry powder inhalers (CEP DPIs) (30 mg/kg) were sprayed into the lungs of rats with ALI via the trachea. Compared with the model group, the treatment group exhibited a reduced pulmonary edema and hemorrhage, and significantly reduced content of inflammatory factors (TNF-α, IL-6 and total protein) in their lungs (p < 0.01), indicating that the main mechanism of CEP underlying the treatment of ALI is anti-inflammation. Overall, the dry powder inhaler can deliver the drug directly to the site of the disease, increasing the intrapulmonary utilization of CEP and improving its efficacy, making it a promising inhalable formulation for the treatment of ALI.