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Aim: The aim of the study was to explore how families' perceptions of dying patients' prognosis awareness influence families' grief. Design: A cross‐sectional design was adopted. Method: Data were collected from a survey of family caregivers of deceased patients through a tertiary hospital in Mainland China between October 2018 and April 2021. One question asked about families' perceptions of patients' awareness of their prognosis, and the Chinese Grief Reaction Assessment Form was used to measure grief. A multiple linear regression with control variables was run to test the link. Missing data were handled with multiple imputation. Results: A total of 181 participants were involved in the analyses. After whether the patient received professional end‐of‐life care in the last days, the place of death and several basic information variables were controlled, families' grief was more intense when they were sure that patients were unaware of the terminal prognosis compared to when they believed that patients were aware or not sure about the patient's awareness. The latter two groups did not differ significantly in grief intensity. Conclusion: For Chinese family caregivers in the present study, terminal patients' awareness of their prognosis is more beneficial than harmful to their bereavement adaptation. This raises empirical concerns over the assumption that truth is harmful and the nondisclosure pattern on such a basis. Impact The findings extend knowledge on the outcomes of information disclosure from the perspective of bereaved family caregivers. Meanwhile, it informs services for the dying and the bereaved: When making decisions about prognosis disclosure to terminally ill patients, potential impacts on not only patients but also families need to be fully considered. For families who are sure that the patient was never aware of the prognosis, additional support ought to be provided to address their intense grief reactions. Patient or Public Contribution: Several professional caregivers helped revise the questionnaire. [ABSTRACT FROM AUTHOR]

Objective: Immunoglobulin A vasculitis (IgAV) is a systemic small vessel vasculitis common in children. Pancreatic involvement in IgAV is rare. The purpose of this study was to analyze the clinical characteristics of IgAV-related acute pancreatitis in children. Methods: Records of patients with IgAV-related acute pancreatitis admitted to our institution between January 2016 and December 2019 were reviewed. We summarized the clinical characteristics, laboratory characteristics, imaging findings, treatment, and outcomes of 15 children with IgAV-related acute pancreatitis. Results: The patients' median age was 9.6 years. Pancreatitis was the initial manifestation of IgAV in 3 patients. All patients had abdominal manifestations, including abdominal pain (15/15), vomiting (10/15), and gastrointestinal bleeding (7/15). Serum amylase and lipase levels were elevated in all patients. Serum amylase in 4 cases reached more than three-fold elevation and serum lipase in 14 cases reached more than three-fold elevation. Morphological abnormalities and abnormal signals of the pancreas were observed in 13 cases by magnetic resonance imaging. Pancreaticobiliary maljunction was seen in 3 cases by magnetic resonance cholangiopancreatography. Glucocorticoid therapy and intravenous immunoglobulins were used to treat acute pancreatitis in IgAV. All patients showed clinical improvement after treatment. During the follow-up period of 6–12 months, all 15 cases with pancreatitis were cured without recurrence. Conclusions: Pancreatic involvement is rare in IgAV; however, this should be considered in IgAV patients with severe abdominal pain. The timely application of steroid therapy is important for IgAV-associated pancreatitis. Key Points • Acute pancreatitis is a rare complication of immunoglobulin A vasculitis (IgAV). • Acute pancreatitis can be the initial manifestation of IgAV. It is important to evaluate for pancreatitis while IgAV patients with severe abdominal pain. • A common image finding of IgAV-associated pancreatitis was swelling of the pancreas. • Glucocorticoid therapy and intravenous immunoglobulins is helpful in alleviating acute pancreatitis in IgAV. [ABSTRACT FROM AUTHOR]

This study aims to identify the factors that influence Chinese professional caregivers' bereavement experiences after patient deaths. Through a content analysis, the study reanalyzed the qualitative data initially collected to understand the lived experiences of professional bereavement in Mainland China. Specifically, the study assessed semi-structured interview transcripts conducted with 24 Chinese physicians and nurses and generated 15 open codes, reflecting the influencing factors. These were further categorized into four themes: dying and death conditions, professional caregivers' characteristics, professional caregivers' involvement, and the bereaved family. The results revealed that professional bereavement experiences and the unveiled factors relate to both the personal and professional lives of the interviewees. Overall, the health care system and cultural backgrounds should be listed as influencing factors for professional bereavement experiences in addition to the aforementioned four. [ABSTRACT FROM AUTHOR]

This study examined the effects of the continuation task and the reading plus continued cloze (RCC) task on Japanese as a foreign language (JFL) vocabulary learning with a view to shedding fresh light on the relationship among depth of processing, interaction, alignment, and learning effects. Three classes of beginning-level JFL learners were randomly assigned to a continuation group, a RCC group, and a control group. A meaning recall test and an oral form recall test were used to gauge vocabulary learning gains. It was found that (i) both tasks led to significant immediate and long-term gains on both the oral form test and the meaning test and (ii) the continuation task showed superiority over the RCC task in promoting JFL vocabulary learning. Implications of these results for JFL vocabulary teaching are discussed. [ABSTRACT FROM AUTHOR]

Immunoglobulin A vasculitis (IgAV), also known as Henoch-Schönlein Purpura, is one of the most common kind of systemic vasculitis in children, and due to the involvement of small blood vessels throughout the body, this disease can cause a variety of symptoms in different organs. Our aim was to review the data on various systemic manifestations of IgAV. A research of the literature was performed in PubMed database, utilizing the MeSH terms "IgA vasculitis" and "Henoch Schönlein Purpura". According to the predetermined structure of the manuscript, we extracted and sorted out the relevant data. Clinically, almost all the patients will present with palpable skin purpura, together with arthritis, gastrointestinal tract involvement, or kidney damage. Other rare systemic manifestations include neurological symptoms, scrotal involvement, and cardiopulmonary disease. When uncommon complications occur, patients may be misdiagnosed as other diseases, thus delaying treatment. Although the course of IgAV is mostly self-limited, misdiagnosis can also lead to a poor prognosis. A comprehensive awareness to the clinical manifestations of IgAV is the necessary prerequisite for its timely diagnosis. Prompt diagnosis and adequate treatment are essential for optimal results. [ABSTRACT FROM AUTHOR]

2D graphene with high quality holds great promise in improving the performance of the hydrogels owing to its exceptional electronic, thermal, and mechanical properties. However, the structure defects existed in graphene restrict its further applications. Herein, a simple and green method of fabricating defect‐free graphene nanosheets with the assistance of supercritical carbon dioxide (SC CO2) is designed. The graphene nanosheets directly assemble with acrylic acid monomer and clay, and a flexible semitransparent hydrogel is fabricated. Benefiting from the excellent properties of the defect‐free graphene, the hydrogel exhibits the high mechanical performance, superfast self‐healing capability, excellent conductivity, and super photothermal conversion efficiency. According to the advantages above, the graphene/poly(acrylic acid)/clay hydrogels can be used for intelligent sensors for disease diagnosis, artificial electronic skin, and military stealth materials in the near future. [ABSTRACT FROM AUTHOR]

To elucidate the effect of 1-Methylcyclopropene (1-MCP) treatment on molecular and nutritional quality changes during 'Qingcui' plum fruit ripening, metabolomic profiling and transcriptome analysis were conducted to identify key metabolites and differentially expressed genes. Application of 1-MCP suppressed 'Qingcui' plum fruit softening and maintained higher soluble solids content. Metabolome profiling identified numerous metabolites that differentially accumulated during ripening and significantly contributed to the nutritional quality of plum fruit. These included sugars, organic acids, amino acids, and phenolic compounds. A special focus was given to twelve phenolic-related metabolites that were reduced by 1-MCP treatment during ripening. Transcriptome profiling revealed the enrichment of transcription factors and biosynthetic genes related to phenolic-related metabolites among differentially expressed genes, indicating that 1-MCP likely influences phenolic-related metabolite levels through transcriptional regulation of their biosynthetic pathways. This integrated analysis of metabolome and transcriptome data provides new insights into the complex mechanisms controlling the nutritional quality of 'Qingcui' plum fruit in response to 1-MCP. Understanding the regulatory networks influencing plum fruit ripening can be valuable for enhancing its nutritional value and facilitating future plum breeding efforts. • 1-MCP suppressed 'Qingcui' plum fruit softening and maintains total soluble solids. • Metabolome and transcriptome analysis of nutritional quality changes in plum fruit. • Phenolic-related metabolites were notably accumulated during 'Qingcui' plum ripening. • 1-MCP reduced the accumulation of phenolic-related metabolites during plum ripening. • 1-MCP suppressed the transcripts of phenolic-related metabolites biosynthetic genes. [ABSTRACT FROM AUTHOR]

• Various forms of dissolved trace elements were distinguished using AF4-UV-ICPMS. • Primarily ionic and colloid-associated forms of Al, As, Co, Cu, Fe, Ni, Pb, Th, Tl, U, V and Zn were extracted with water. • Mainly ionic species of Ba, Cr, Li, Mn and Mo were found in both extracts. • Primarily ionic forms of all elements were present in CaCl 2 extracts. Dissolved (<0.45 µm) trace elements (TEs) represent the sum of free ions, simple complexes and colloid-associated forms which have different mobility and bioavailability in soils. The distribution of TEs amongst these chemical forms was directly quantified in soil extracts using asymmetric flow field-flow fractionation (AF4) coupled to ultraviolet–visible absorbance spectrophotometry (UV) and inductively coupled plasma mass spectrometry (ICP-MS). The soil extracts were obtained using single extraction method with water and 0.01 M CaCl 2 , respectively. The yields of dissolved TEs extracted from the soils were profoundly impacted by extractants. Using AF4-UV-ICPMS, we show that dissolved species of Ba, Cr, Li, Mn and Mo were primarily present as "truly dissolved"/mainly ionic species (<1 kDa), e.g., hydrated cations, simple complexes or oxyanions, and therefore, likely represented the most bioavailable fraction. The distribution of these TEs amongst dissolved forms was unaffected by the different extractants. However, their dissolved concentrations were profoundly affected. Distributions of Al, As, Co, Cu, Fe, Ni, Pb, Th, Tl, U, V and Zn among the various chemical forms significantly differed with water and CaCl 2 extractants. In water extracts, a greater proportion of these elements was associated with colloidal forms having sizes from 1 kDa to 0.45 µm, i.e., dissolved organic matter (DOM) or/and inorganic colloids. Water not only released greater colloid-complexed concentrations of TEs, like Al, As, Fe, Pb, Th, Tl, U and V, but also liberated greater amounts associated with ionic and small forms. Extractants like water and CaCl 2 are useful for recovering bioavailable TEs from soils. However, the dissolved TEs extracted using water or CaCl 2 represented TE concentrations and forms with different bioavailability. The AF4-UV-ICPMS technique is useful for directly quantifying TEs existing as mainly ionic species and those bound with DOM and inorganic colloids, and thus offers clear insight into their bioavailability in soils. This method also facilitates a better understanding of the effects of extractants on estimating TE bioavailability. [ABSTRACT FROM AUTHOR]

The current knowledge about early-life nutrition and environmental factors that affect the interaction between the symbiotic microbiota and the host immune system has demonstrated novel regulatory target for treating allergic diseases, autoimmune disorders and metabolic syndrome. Various kinds of food nutrients (such as dietary fiber, starch, polyphenols and proteins) can provide energy resources for both intestinal microbiota and the host. The indigestible food components are fermented by the indigenous gut microbiota to produce diverse metabolites, including short-chain fatty acids, bile acids and trimethylamine-N-oxide, which can regulate the host metabolized physiology, immunity homeostasis and health state. Therefore it is commonly believed early-life perturbation of the microbial community structure and the dietary nutrition interference on the child mucosal immunity contribute to the whole life susceptibility to chronic diseases. In all, the combined interrelationship between food ingredients nutrition, intestinal microbiota configurations and host system immunity provides new therapeutic targets to treat various kinds of pathogenic inflammations and chronic diseases. [ABSTRACT FROM AUTHOR]

Superficial scald is a significant physiological disorder causing economic loss to the apple and pear fruit industry. Despite treatments to prevent the scald, fundamental biochemical knowledge about the injury is not completely known. To investigate the protein changes in association with scald development during storage and in response to treatments of diphenylamine and 1-MCP, two quantitative proteomic experiments employing stable isotope labeling by peptide dimethylation were conducted on two scald susceptible cultivars ‘Cortland’ and ‘Red Delicious’. Apples were untreated or treated with 2 g L −1 DPA or with/without 1 μL L −1 1-MCP, then stored at CA (3.0 kPa O 2 + 1.0 kPa CO 2 ) at 0–1 °C for up to 7 months. Among the quantified proteins, 428 proteins were common to both cultivars and 110 increased in abundance and 48 decreased during the onset of scald development. Fifty seven and 67 proteins changed significantly in abundance in response to DPA and 1-MCP treatments after 4 and 7 months storage, respectively. When combining the results from both cultivars, 14 proteins increased in abundances and 4 proteins decreased in abundance with scald development but inhibited and enhanced by both DPA and 1-MCP treatments, respectively, which were proposed to be in association with scald development of apples. Our results reveal and confirm that antioxidant and redox system, phenylpropanoid metabolism, ethylene biosynthesis, allergens, sulfur amino acids containing proteins and program cell death have direct link to the scald development. [ABSTRACT FROM AUTHOR]

Anti-HIV prodrugs are recently focused on due to their ability of self-assembly, macrophage targeting, and enhanced antiviral effects. Here, an amphiphilic prodrug of zidovudine, an anti-HIV nucleoside analogue, 5′-cholesteryl-ethyl-phosphoryl zidovudine (CEPZ) was synthesized. CEPZ showed some unique physicochemical properties. The solubility of CEPZ in the noncompetitive solvents chloroform and tetrahydrofuran (THF) was very high based on the hydrogen bonds between zidovudine groups, though CEPZ was sparing soluble in alcohols and almost insoluble in water. The typical amphiphilic property of CEPZ was demonstrated according to the Langmuir monolayers at the air/water interface. The Log P of CEPZ was high to 13.78, indicating the high hydrophobicity of amphiphilic CEPZ similar to phospholipids. Homogenous and stable self-assemblies were formed with the mean size of 128.7 nm and the zeta potential of −35.4 mV after injecting the CEPZ-in-THF solution into water. Hydrophobic interaction between the cholesteryl moieties of CEPZ could drive molecular self-assembly and lead to the formation of spherical vesicles. CEPZ self-assemblies showed strong stability even under high temperature and gravity probably due to the high surface charge. CEPZ was very slowly degraded in neutral solutions (e.g., pH 7.4), but fast in acid solutions (e.g., pH 5.0) and some tissue homogenates. CEPZ was quickly eliminated from the circulation and distributed into the mononuclear phagocyte system (MPS) including the liver, spleen and lung after bolus intravenous administration of CEPZ self-assemblies to mice. The MPS targeting effect of CEPZ self-assemblies makes them become a promising self-assembled drug delivery system to eradicate the HIV hidden in the macrophages. [ABSTRACT FROM AUTHOR]

Probenecid and N-acetylcysteine (NAC) can preserve intracellular levels of the vital antioxidant glutathione (GSH) via two distinct biochemical pathways. Probenecid inhibits transporter-mediated GSH efflux and NAC serves as a cysteine donor for GSH synthesis. We hypothesized that probenecid and NAC alone would maintain intracellular GSH concentrations and inhibit neuronal death after traumatic stretch injury, and that the drugs in combination would produce additive effects. Sex-segregated rat primary cortical neurons were treated with probenecid (100 μM) and NAC (50 μM), alone and in combination (Pro-NAC), then subjected to mechanical stretch (10s−1 strain rate, 50% membrane deformation). At 24 h, both probenecid and NAC inhibited trauma-induced intracellular GSH depletion, lactate dehydrogenase (LDH) release, and propidium iodide (PI) uptake in both XY- and XX-neurons. Combined Pro-NAC treatment was superior to probenecid or NAC alone in maintenance of intracellular GSH and neuronal death assessed by PI uptake. Interestingly, caspase 3 activity 24 h after mechanical trauma was more prominent in XX-neurons, and treatment effects (probenecid, NAC, and Pro-NAC) were observed in XX- but not XY-neurons; however, XY-neurons were ultimately more vulnerable to mechanical stretch-induced injury than their XX counterparts, as was evidenced by more neuronal death detected by LDH release and PI uptake. In addition, after stretch injury in HT22 hippocampal cells, both NAC and probenecid were highly effective at reducing oxidative stress detected by dichlorofluorescein fluorescence. These in vitro data support further testing of this drug combination in models of traumatic neuronal injury in vivo. [ABSTRACT FROM AUTHOR]

Context: Melanoma therapy absorbs attention because of the high morbidity and mortality. However, currently systematic administrations could take little therapeutic efficiency and severe side effects. Objective: An effective transdermal formulation for the convenient melanoma therapy was found and evaluated. Materials and methods: A mitoxantrone (MTO) cubic phase was prepared with glyceryl monooleate, ethanol and water. The permeation, cytotoxicity,in vivoanti-melanoma effect of the MTO cubic phases were evaluated. The anti-cancer mechanism of the MTO cubic phases was explored according to the immunohistochemistry and flow cytometry. Results and discussion: The isotropic structure of MTO cubic phases was identified. The transdermal permeability of MTO was greatly improved by the cubic phase compared to that of the MTO solution. The MTO cubic phases showed the high cytotoxicity in B16melanoma cells evidenced by a modified electrical cell–substrate impedance sensing system. High anti-melanoma effect of the MTO cubic phases was confirmed according to the tumor volume changes and tumor weight. The tumor inhibitory rate of the MTO cubic phases was 68.44%. The calreticulin expression of B16cells was improved by the MTO cubic phases, and the improved cell uptake of MTO was confirmed by the flow cytometry. Conclusion: The MTO cubic phase is a promising topical delivery system for melanoma therapy with the advantages of non-invasion and no severe side effects. [ABSTRACT FROM PUBLISHER]

Hepatocellular carcinoma (HCC) is a serious cancer with high mortality worldwide. Gemcitabine (GEM) is easily degraded in the circulation and has no tumor-targeted effect. In our previous research, an amphiphilic GEM derivative, cyclic phosphoryl N- dodecanoyl gemcitabine (CPDG) was prepared based on the techniques of HepDirect prodrug and self-assembled drug delivery systems (SADDS), which self-assembled into the stable nanoassemblies in water. In this study, the long-circulating nanoassemblies of CPDG/CHS-PEG1500 (9:1, mol/mol) were prepared for HCC treatment. In vitro and in vivo studies of the long-circulating CPDG nanoassemblies were explored. The degradation rates of CPDG depended on the media. CPDG showed much faster degradation in the acidic environment (pH 2.0) than the weak acidic and neutral media (pH 5.0, pH 7.4). However, the degradation half-life ( t 1/2 ) of CPDG was about 43 h in the mouse plasma, longer than the t 1/2 at pH 2.0. Therefore, the long-circulating CPDG nanoassemblies could keep stable before reaching the targets in vivo . In the biodistribution study, the long-circulating CPDG nanoassemblies were bolus intravenously ( i.v. ) injected into the hepatocellular tumor-bearing mice. The distribution of CPDG in the tumors was much higher than that in the blood, indicating the tumor targeting of the long-circulating nanoassemblies. In the pharmacodynamic study, the long-circulating CPDG nanoassemblies were i.v. injected into the tumor-bearing mice with doses of (37.5, 75 μmol/kg) compared with GEM (150 μmol/kg). The mice were injected once every 3 days for totally 3 times. The long-circulating nanoassemblies nearly always showed the higher anti-cancer effects than GEM. The tumor inhibitory rates of GEM, the long circulating CPDG nanoassemblies (37.5, 75 μmol/kg) were 49.54, 42.97, 65.10%, respectively. Therefore, the long-circulating CPDG nanoassemblies had the much higher anti-cancer effect than GEM. The long-circulating CPDG nanoassemblies are promising nanomedicines to treat HCC. The combination design of tumor-targeted nanoassemblies based on HepDirect prodrug technique and SADDS theory is an effective method to modify the pharmacologically active nucleosides to treat some liver diseases. [ABSTRACT FROM AUTHOR]

A targeted quantitative proteomic investigation employing the multiple reaction monitoring (MRM, SRM) technique was conducted on strawberry fruit at different development stages. We investigated 22 proteins and isoforms from 32 peptides with 111 peptide transitions, which may be involved in the volatile aroma biosynthesis pathway. The normalized protein abundance was significantly changed in coincidence with increased volatile production and advanced fruit maturities. Among them, alcohol acyltransferase (AAT), quinone oxidoreductase (QR), malonyl Co-A decarboxylase, (MLYCD), pyruvate decarboxylase (PDC), acetyl Co-A carboxylase (ACCase), and acyl Co-A synthetase (ACAs) were increased significantly. Several alcohol dehydrogenases (ADHs), and 3-oxoacyl-ACP synthase were significantly decreased. Furthermore, the expression of seven genes related to strawberry volatile production was also investigated using real-time qPCR. Among the tested genes, QR , AAT , ACCase , OMT , PDC and ADH showed increased up-regulation during fruit ripening, while 3-isopropylmalate dehydrogenase ( IMD ) decreased. Strong correlation between quantitative proteomic data and gene expression suggested that AAT, QR, ACCase, and PDC played critical roles in volatile biosynthesis of strawberry during fruit ripening. Poor correlation between protein abundance and gene expression of ADH was found. [ABSTRACT FROM AUTHOR]

Ketorolac tromethamine (KT) was potent to treat moderate to moderately severe pains. However, KT solutions for nasal delivery lost quickly from the nasal route. Thermo- and ion-sensitive in-situ hydrogels (ISGs) are appropriate for nasal drug delivery because the intranasal temperature maintains ∼37 °C and nasal fluids consist of plentiful cations. In this study, a novel nasal thermo- and ion-sensitive ISG of KT was prepared with thermo-sensitive poloxamer 407 (P407) and ion-sensitive deacetylated gellan gum (DGG). The optimal formulation of the KT ISG consisted of 3% (w/v) DGG and 18% (w/v) P407 and its viscosity was up to 7.63 Pa s at 37 °C. Furthermore, penetration enhancers and bacterial inhibitors were added and their fractions in the ISG were optimized based on transmucosal efficiencies and toxicity on toad pili. Sulfobutyl ether-β-cyclodextrin of 2.5% (w/v) and chlorobutanol of 0.5% (w/v) were chosen as the penetration enhancer and the bacterial inhibitor, respectively. The Fick’s diffusion and dissolution of KT could drive it continuous release from the dually sensitive ISG according to the in vitro investigation. Two methods, writhing frequencies induced by acetic acid and latency time of tails retracting from hot water, were used to evaluate the pharmacodynamics of the KT ISG on the mouse models. The writhing frequencies significantly decreased and the latency time of tail retracting was obviously prolonged ( p < 0.05) for the KT ISG compared to the control. The thermo- and ion-sensitive KT ISG had appropriate gelation temperature, sustained drug release, improved intranasal absorption, obvious pharmacodynamic effect, and negligible nasal ciliotoxicity. It is a promising intranasal analgesic formulation. [ABSTRACT FROM AUTHOR]

Melanomas are malignant tumors characterized by early metastasis, rapid development, poor prognosis and high mortality. A highly effective and convenient method is necessary for long-term treatment of melanomas. Mitoxantrone (MTO) was topically applied for melanoma therapy using an MTO ethosome gel. Firstly, an ethosome was prepared from MTO, phospholipids, ethanol and water followed by addition of hydroxypropyl methylcellulose to obtain an ethosome gel. The ethosome was characterized. The cytotoxicity on B 16 melanoma cells was evaluated on an electrical cell-substrate impedance sensing system with a novel modified chip. In vivo anti-melanoma effect of the ethosome gel was explored. Immunohistochemical and flow cytometric investigations were done. The MTO ethosomes had the size of 78 nm and the zeta potential of −55 mV. The ethosomes were flexible vesicles and showed much higher in vitro permeability across the rat skin than MTO aqueous solutions. The ethosomes had significant cytotoxicity and higher in vivo anti-melanoma effect than MTO solutions. The calreticulin membrane translocation of B 16 cells was improved by the MTO ethosomes and the cell uptake of MTO was confirmed. The MTO ethosome gel is a promising transdermal delivery system for melanoma therapy with the advantages of non-invasion and no significant side effects. [ABSTRACT FROM AUTHOR]

To better understand the regulation of flavonoid and anthocyanin biosynthesis, a targeted quantitative proteomic investigation employing LC-MS with multiple reaction monitoring was conducted on two strawberry cultivars at three ripening stages. This quantitative proteomic workflow was improved through an OFFGEL electrophoresis to fractionate peptides from total protein digests. A total of 154 peptide transitions from 47 peptides covering 21 proteins and isoforms related to anthocyanin biosynthesis were investigated. The normalized protein abundance, which was measured using isotopically-labeled standards, was significantly changed concurrently with increased anthocyanin content and advanced fruit maturity. The protein abundance of phenylalanine ammonia-lyase; anthocyanidin synthase, chalcone isomerase; flavanone 3-hydroxylase; dihydroflavonol 4-reductase, UDP-glucose:flavonoid-3-O-glucosyltransferase, cytochrome c and cytochrome C oxidase subunit 2, was all significantly increased in fruit of more advanced ripeness. An interaction between cultivar and maturity was also shown with respect to chalcone isomerase. The good correlation between protein abundance and anthocyanin content suggested that a metabolic control point may exist for anthocyanin biosynthesis. This research provides insights into the process of anthocyanin formation in strawberry fruit at the level of protein concentration and reveals possible candidates in the regulation of anthocyanin formation during fruit ripening. Biological significance To gain insight into the molecular mechanisms contributing to flavonoids and anthocyanin biosynthesis and regulation of strawberry fruit during ripening is challenging due to limited molecular biology tools and established hypothesis. Our targeted proteomic approach employing LC-MS/MS analysis and MRM technique to quantify proteins in relation to flavonoids and anthocyanin biosynthesis and regulation in strawberry fruit during fruit ripening is novel. The identification of peptides and proteins provided reliable design and validation of quantitative approaches using SRM on targeted proteins proposed involved in strawberry fruit. Our data revealed the identifying candidate proteins and their quantitative changes in relation to fruit ripening and flavonoids and anthocyanin biosynthesis and regulation. More importantly, this quantitative proteomic data is also compared with chemical analysis to reveal possible control levels of this important quality trait. Although, MRM approach is not new in plant biology research, the application has been very rare. This is the first systematic multi-targeted interrogation of the possible regulation of entire pathway of flavonoids and anthocyanin biosynthesis in strawberry fruit at different ripening stages using quantitative MRM technique on mass spectrometry. Our results demonstrate the power of targeted quantitative mass spectrometry data for analysis of proteins in biological regulation. These results indicate that distinct and diverse control of flavonoids and anthocyanin biosynthesis mechanisms at metabolism and proteins levels. This important and complementary knowledge will be useful for systematically characterizing the flavonoids and anthocyanin biosynthesis pathway of any fruit/plant species. [ABSTRACT FROM AUTHOR]

Splicing factors (SFs) coordinate nuclear intron/exon splicing of RNA. Splicing factor disturbances can cause cell death. RNA binding motif 5 (RBM5) and 10 (RBM10) promote apoptosis in cancer cells by activating detrimental alternative splicing of key death/survival genes. The role(s) of RBM5/10 in neurons has not been established. Here, we report that RBM5 knockdown in human neuronal cells decreases caspase activation by staurosporine. In contrast, RBM10 knockdown augments caspase activation. To determine whether brain injury alters RBM signaling, we measured RBM5/10 protein in mouse cortical/hippocampus homogenates after controlled cortical impact (CCI) traumatic brain injury (TBI) plus hemorrhagic shock (CCI+HS). The RBM5/10 staining was higher 48 to 72 hours after injury and appeared to be increased in neuronal nuclei of the hippocampus. We also measured levels of other nuclear SFs known to be essential for cellular viability and report that splicing factor 1 (SF1) but not splicing factor 3A (SF3A) decreased 4 to 72 hours after injury. Finally, we confirm that RBM5/10 regulate protein expression of several target genes including caspase-2, cellular FLICE-like inhibitory protein (c-FLIP), LETM1 Domain-Containing Protein 1 (LETMD1), and amyloid precursor-like protein 2 (APLP2) in neuronal cells. Knockdown of RBM5 appeared to increase expression of c-FLIP(s), LETMD1, and APLP2 but decrease caspase-2. [ABSTRACT FROM AUTHOR]

Bananas ( Musa , AAA group) develop a bright yellow appearance when ripen at temperatures between 18 °C and 24 °C. At high ambient temperatures, the fruit display green-ripe and become un-acceptable in the market. To understand the mechanisms that govern the color changing during banana green-ripening, the influence of high temperature on chlorophyll degradation at various ripening stages were investigated. After ripening initiation, the fruit were subjected to 8 different temperature changing regimes at both 20 °C and 30 °C in 5 days. The ripening and senescence parameters were monitored and relevant gene expression was analyzed by RNA gel blot hybridization. Temperature during the first 3 days, or precisely the stage around the on-set of the respiration peak, was found to be critical for color formation in bananas. When the fruit were held at 30 °C at this stage, the fruit developed green-ripe with >30% of the original chlorophyll remaining, regardless the other stages were at 20 °C. The repressed chlorophyll degradation by 30 °C was positively correlated to the reduced expression of several key genes functioning in chlorophyll degradation, MaSGR , MaNYC and MaPaO , which behaved in a closely temperature responding manner. Conversely to chlorophyll degradation patterns, moving to 30 °C induced fruit respiration rate, the expression of MaACO , an ethylene synthesis related gene, and accelerated the decrease in fruit firmness and chlorophyll florescence ( F v / F m ), indicating that the ripening of the fruit was accelerated at 30 °C. Accordingly, in the context of fruit ripening but under not agreeable temperature (30 °C), the expression of chlorophyll degradation genes in bananas was predominantly regulated by temperature, not responding to the fruit ripening proceeding. Interestingly, by using the alternating temperature system, we here the first time reported the sensitivity of chlorophyll degradation genes, MaSGR , MaPAO and MaNYC , to high temperature during banana fruit ripening. [ABSTRACT FROM AUTHOR]

Abstract: Curcumin (Cur) is a hydrophobic polyphenol with diverse pharmacological effects, especially for cancer treatment. However, its weak water solubility and stability was the major obstacle for the formulation research of Cur. The complexation of Cur and hydroxypropyl-β-cyclodextrin (HP-β-CD) was done by grinding. The increasing solubility of Cur was achieved due to complexation and the photochemical stability of Cur was improved. The inclusion of Cur could happen when two ends of Cur were embedded into the cavity of the HP-β-CD rings. The in situ hydrogels (ISGs) of Cur and its inclusion complexes were prepared using poloxamers 407 and 188 as the matrix. The extent of drug’s in vitro release from the ISGs depended on the dissolution of drugs. Both of the ISGs had transdermal effect and cytotoxicity on B16-F10 cells. However, the effects of the ISGs containing Cur inclusion complexes were much higher than those of Cur ISGs because of the improved Cur solubility in the former. The cytotoxicity of Cur on melanoma cells was related to blocking of cellular proliferation in the G2/M stage followed by cellular apoptosis. The ISGs of Cur inclusion complexes are a promising formulation for melanoma treatment. [Copyright &y& Elsevier]

Abstract: The aim of this study was to prepare riboflavin laurate (RFL) nanosuspensions as an intramuscular injection for long-term riboflavin supplementation. Stable RFL nanosuspensions were obtained by injecting RFL/poloxamer solution in N,N-dimethyl formamide into a trehalose solution. Long soft nanostructures initially appeared and then tube-like rigid nanostructures were obtained after removal of solvents according to the transmission electron microscopic images. The nanosuspensions had narrow size distribution and the mean size was about 300nm. Molecular self-assembly of RFL may drive the formation of nanostructures. RFL formed a monolayer at the air/water interface and poloxamer 188 could insert into the monolayer. The nanosuspensions were intramuscularly injected into rats to provide long-term riboflavin supplementation for more than 30 days in light of body weight, food intake, and urinary riboflavin. The nanosuspensions were also used to resist the riboflavin deficiency induced by methotrexate chemotherapy. RFL nanosuspensions are a promising nanomedicine for long-term riboflavin supplementation. [Copyright &y& Elsevier]

We investigated the phylogeny of the viviparid genus Margarya, endemic to Yunnan, China, using two mitochondrial gene fragments (COI and 16S rRNA). The molecular phylogeny based on the combined dataset indicates that Margarya is polyphyletic, as two of the three well-supported clades containing species of Margarya also comprise species from other viviparid genera. In one clade, sequences of four species of Margarya even cluster indiscriminately with those of two species of Cipangopaludina, indicating that the current state of Asian viviparid taxonomy needs to be revised. Additionally, these data suggest that shell evolution in viviparids is complex, as even the large and strongly sculptured shells of Margarya, which are outstanding among Asian viviparids, can apparently be easily converted to simple smooth shells. The molecular data also indicate that the species status of the six extant species of Margarya should be re-assessed. [ABSTRACT FROM AUTHOR]

In this study, a multifunctional in situ-forming hydrogel ( MISG) was prepared as a wound dressing designed to stop bleeding, inhibit inflammation, relieve pain, and improve healing. A mixture of poloxamers 407 and 188 was used for the matrix of the MISG. Other ingredients include aminocaproic acid (to stop bleeding), povidone iodine (anti-infective), lidocaine (pain relief), and chitosan (to enhance wound healing and regeneration). The incipient gelation temperature of the MISG was modified by varying the poloxamer concentration. Poloxamer cytotoxicity was evaluated in addition to the effect of the MISG on hemostasis in rabbits, pain relief in mice, bacteriostasis in vitro, and wound healing. The optimal MISG matrix consisted of 30% (w/v) poloxamer (407/188, 1 : 1, w/w) solution and was able to change to a gel within 10 minutes at 37 °C. The poloxamer solution had no cytotoxicity in fibroblasts. Compared to sterile gauze alone, the MISG significantly shortened average hemostasis time and decreased bleeding. The hydrogel showed strong bacteriostatic action similar to povidone iodine solution. It markedly increased the pain threshold and accelerated wound healing compared to the gauze. The MISG is a promising formulation for wound healing in emergency situations. [ABSTRACT FROM AUTHOR]

Abstract: The repeating decapeptides of the mussel adhesive protein (MAP) were considered as the basis for mussel adhesion in wet environment for it contains L-3, 4-dihydroxyphenylalanine (DOPA). However, DOPA residue in the Perna viridis foot protein-1 (Pvfp-1) do not exist in the repeating decapeptide sequence but present in the non-repeating region. Therefore, it is quite necessary to evaluate the adhesive capacity of the repeating and non-repeating regions of Pvfp-1. In this study, the sequence of eight repeating decapeptides (R-240) and the sequence of the non-repeating region (C-237) of Pvfp-1 was amplified and expressed, respectively. With adsorption, adhesion and coating analysis, it was found that the recombinant C-237 has comparable adhesion and coating ability compared with that of Cell-Tak™ (the positive control) and it was also much better than that of R-240, especially on the non-adhesive PTFE surface. Moreover, C-237 exhibited no cytotoxicity and showed better cell adhesion and spreading abilities than that of R-240 on both glass and PTFE surfaces. Therefore, the recombinant C-237 could be used as bioadhesive for medical purpose and be potentially used as an improver for bio-inert materials when applied in biomedical areas. [Copyright &y& Elsevier]

Abstract: A novel ultrasound-responsive doxorubicin (DOX)–loaded nanoparticulate system was prepared in this study. The DOX-loaded polymeric micelles were first prepared using poly(D,L-lactide-co-glycolide)-methoxy-poly(ethylene glycol) (PLGA-mPEG) with a high encapsulation efficiency of 89.2%. After filling with perfluoropentane (boiling point 29°C), the micelles were transformed into nanodroplets that were stable as a result of the PEG shell. The nanodroplets were transformed into nanobubbles at 37°C, and little drug was released if no ultrasound was exerted. Ultrasound-triggered drug release, with pH dependency, was shown. The DOX release percentage was 9.59% at pH 6.5 (also appeared in tumor) and only 2.22% at pH 7.4 after sonicating for 0.5 min at 37°C. The tumor inhibitory rate of Group III (DOX-loaded nanodroplets combined with ultrasound) was 84.3%, more than that of Group II (DOX-loaded nanodroplets), which was 60.4%. Moreover, the nanodroplets showed much lower toxicity than free drugs. The novel nanodroplets could be a promising anticancer drug delivery system. [Copyright &y& Elsevier]

The article examines whether polynitroxylated pegylated hemoglobin (PNPH) represents a neuroprotective hemoglobin-based oxygen carrier for resuscitation of hemorrhagic hypotension after traumatic brain injury. PNPH refers to a non-neurotoxic hemoglobin-based oxygen carrier in neuronal culture and is also neuroprotective in vitro neuronal injury models. The study was conducted in rat primary cortical neuronal cultures. The results of the study revealed that PNPH offers unique advantages for in vitro and in vivo traumatic brain injury resuscitation.

Research on white rot fungi for environmental biotechnology has been conducted for more than 20 years. In this article, we have reviewed processes for cell growth and enzyme production including the factors influencing enzyme productivity and the methods for enhancement of enzyme production. Significant progress has been achieved in molecular biology related to white rot fungi, especially related to the extraction of genetic material (RNA and DNA), gene cloning and the construction of genetically engineered microorganisms. The development of biotechnologies using white rot fungi for environmental pollution control has been implemented to treat various refractory wastes and to bioremediate contaminated soils. The current status and future research needs for fundamentals and application are addressed in this review. [ABSTRACT FROM AUTHOR]

Sex-dependent differences in adaptation to famine have long been appreciated, thought to hinge on female versus male preferences for fat versus protein sources, respectively. However, whether these differences can be reduced to neurons, independent of typical nutrient depots, such as adipose tissue, skeletal muscle, and liver, was heretofore unknown. A vital adaptation to starvation is autophagy, a mechanism for recycling amino acids from organelles and proteins. Here we show that segregated neurons from males in culture are more vulnerable to starvation than neurons from females. Nutrient deprivation decreased mitochondrial respiration, increased autophagosome formation, and produced cell death more profoundly in neurons from males versus females. Starvation-induced neuronal death was attenuated by 3-methyladenine, an inhibitor of autophagy; Atg7 knockdown using small interfering RNA; or L-carnitine, essential for transport of fatty acids into mitochondria, all more effective in neurons from males versus females. Relative tolerance to nutrient deprivation in neurons from females was associated with a marked increase in triglyceride and free fatty acid content and a cytosolic phospholipase A2-dependent increase in formation of lipid droplets. Similar sex differences in sensitivity to nutrient deprivation were seen in fibroblasts. However, although inhibition of autophagy using Atg7 small interfering RNA inhibited cell death during starvation in neurons, it increased cell death in fibroblasts, implying that the role of autophagy during starvation is both sex- and tissue-dependent. Thus, during starvation, neurons from males more readily undergo autophagy and die, whereas neurons from females mobilize fatty acids, accumulate triglycerides, form lipid droplets, and survive longer. [ABSTRACT FROM AUTHOR]

Many central nervous system (CNS) diseases display sexual dimorphism. Exposure to circulating sex steroids is felt to be a chief contributor to this phenomenon; however, CNS diseases of childhood and the elderly also demonstrate gender predominance and/or a sexually dimorphic response to therapies. Here we show that XY and XX neurons cultured separately are differentially susceptible to various cytotoxic agents and treatments. XY neurons were more sensitive to nitrosative stress and excitotoxicity versus XX neurons. In contrast, XX neurons were more sensitive to etoposide- and staurosporine-induced apoptosis versus XY neurons. The responses to specific therapies were also sexually dimorphic. Moreover, gender proclivity in programmed cell death pathway was observed. After cytotoxic challenge, programmed cell death proceeded predominately via an apoptosis-inducing factor-dependent pathway in XY neurons versus a cytochrome c-dependent pathway in XX neurons. This gender-dependent susceptibility is related to the incapacity of XY neurons to maintain intracellular levels of reduced glutathione. In vivo studies further demonstrated an incapacity for male, but not female, 17-day-old rats to maintain reduced glutathione levels within cerebral cortex acutely after an 8-min asphyxial cardiac arrest. This gender difference in sensitivity to cytotoxic agents may be generalized to nonneuronal cells, as splenocytes from male and female 16-18-day-old rats show similar gender-dependent responses to nitrosative stress and staurosporine-induced apoptosis. These data support gender stratification in the evaluation of mechanisms and treatment of CNS disease, particularly those where glutathione may play a role in detoxification, such as Parkinson's disease, traumatic brain injury, and conditions producing cerebrai ischemia, and may apply to non-CNS diseases as well. [ABSTRACT FROM AUTHOR]

Discusses a study which verified the presence of poly(ADP-ribose) polymerase-1 (PARP-1) and poly(ADP-ribosylation) within mitochondrial fractions from primary cortical neurons and fibroblasts. Inhibition of poly(ADP-ribosylation) within the mitochondrial compartment; Prevention of the release of apoptosis-inducing factor; Reduction of neuronal cell death triggered by oxidative stress.

Cepharanthine is an active ingredient separated and extracted from Stephania cepharantha Hayata, a Menispermaceae plant. As a bisbenzylisoquinoline alkaloid, cepharanthine has various pharmacological properties, including antioxidant, anti-inflammatory, immunomodulatory, antitumoral, and antiviral effects. Following the emergence of coronavirus disease 2019 (COVID-19), cepharanthine has been found to have excellent anti-COVID-19 activity. In this review, the important physicochemical properties and pharmacological effects of cepharanthine, particularly the antiviral effect, are systematically described. Additionally, the molecular mechanisms and novel dosage formulations for the efficient, safe, and convenient delivery of cepharanthine are summarized. [ABSTRACT FROM AUTHOR]

Sulfur–heteroatom bonds, such as S–N bonds, are valuable motifs in pharmaceuticals and agrochemicals, but the creation of new green synthetic methods to construct these compounds via rational design of catalysts remains challenging. Hence, we report an environmentally benign photocatalytic S–N coupling reaction between thiols and amines over carbon-doped potassium poly(heptazine imide), resulting in the synthesis of sulfenamides. Encouragingly, after optimizing the C-doping content of potassium poly(heptazine imide), we can achieve high sulfenamide conversion rates of 92% (10 W white LED, 24 h) and 86% (real sunlight irradiation in summer, 5 h). Moreover, the present catalyst possesses good substrate tolerance for the photocatalytic S–N coupling of thiols and amine derivatives, great recyclability, and a gram-scale synthesis was also possible. We provide good evidence that the carbon-doping of potassium poly(heptazine imide) can extend its optical absorption range to near-infrared light while inhibiting the intrinsic radiative recombination of photoexcited electron–hole pairs and facilitating the single electron transfer process owing to its delocalized electron density. Overall, boosting the photosynthetic sulfenamide activity by introducing delocalized electrons is demonstrated, and this could be applied more widely in heterogeneous photocatalysis in organic synthesis. [ABSTRACT FROM AUTHOR]

The distribution and speciation of dissolved (<0.45 µm) trace elements (TEs) in soils have implications for their availability, accessibility, and toxicity due to the distinct behavior of each species. The application of manure and inorganic fertilizer play a key role in the speciation of TEs in soil solutions, which also depends on the chemical properties of the elements and soil factors (e.g. moisture content, pH, redox potential, ionic strength, organic matter concentrations and soil texture). In this study we characterized the distribution of TE species in soil solutions using asymmetrical flow field-flow fractionation (AF4) coupled to UV-Visible absorption (UV) and ICP-MS, and examined the impacts of manure, inorganic fertilizer and soil properties on TE speciation. AF4-UV-ICPMS is a powerful method for measuring the distribution of TEs among primarily ionic and small species < 1 nm, organic-dominated colloids, and primarily inorganic colloids on the basis of molecular size. Eight soil treatments were chosen from the University of Alberta Breton Plots and associated Bentley Forest Reserve, including the control, NPKS inorganic fertilizer, and manure treatments, applied under different crop rotations (2-year of wheat-fallow rotation and 5-year of cereal-forage rotation), and the pristine forest (never cultivated). Soil solutions were collected under vacuum using surgical (316) stainless steel lysimeters (5 micron pore size), after irrigating with high purity water (deionized, type II Milli-Q). Analyses were performed in the metal-free, ultraclean SWAMP lab. The acid-cleaned lysimeters yielded excellent blank values for most of trace elements of environmental interest (Li, Al, Mn, Co, Ni, Cu, As, Mo, Cd, Ba, Tl, Pb, Th and U). Using the new lysimeter combined with AF4-UV-ICPMS, we provide a new perspective on TE speciation in soil solutions, with a view towards understanding the effect of long-term fertilization on the bioavailability of micronutrients and potentially toxic trace elements. [ABSTRACT FROM AUTHOR]

Taxonomy and species boundaries within the Rhacophorus rhodopus and Rhacophorus bipunctatus complexes are very confusing. In this study, we attempt to delimit the species boundaries and test the currently accepted taxonomic assignments within these two complexes based on newly collected samples and previously published data across their distributions. Phylogenetic analyses revealed that the R. rhodopus and R. bipunctatus complexes consisted of six distinct clades (labeled A‒F) that diverged from each other by genetic distances (p-distance) ranging from 5.3% to 9.2% in 16S rRNA sequences, and accordingly analyses of species delimitation placed them into six species, of which three correspond to known species (R. rhodopus, R. bipunctatus, and R. napoensis) and three represent different cryptic species. Rhacophorus rhodopus (Clade C) is distributed in southern Yunnan, China, northern Laos, and northern and central Thailand; R. bipunctatus (Clade F) is distributed in northeastern India and western and northern Myanmar; and R. napoensis (Clade B) is distributed in Guangxi, China and northern Vietnam. Based on both molecular and morphological evidence, we described the clade consisting of samples from Hainan, China and central Vietnam (Clade A) as a new species, Rhacophorus qiongica sp. nov. There are two cryptic species requiring additional morphological studies: one only contains samples from Motuo, Xizang, China (Clade E), and the other is distributed in western Yunnan, China, central Myanmar, central Thailand, and Malaysia (Clade D). Additionally, our results supported the idea that some old GenBank sequences of R. reinwardtii need to be updated with the correct species name. [ABSTRACT FROM AUTHOR]

Simple Summary: At present, there are two hypotheses about the biogeographic origin of Kurixalus on the East Asian islands. We reconstructed the ancestral distribution of Kurixalus, based on complete sampling and accurate selection of biogeographical analysis models. The results showed that Kurixalus on the East Asian islands have originated from the Asian mainland through two long-distance colonization events (jump dispersal). In addition, the analyses of the tempo of diversification revealed that the diversification rate of Kurixalus showed a slight decreasing trend. The relevant results will help us to comprehensively and accurately understand the geographical origin of Kurixalus and improve our understanding of the origin history of the flora and fauna of Taiwan Island. 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. [ABSTRACT FROM AUTHOR]

To gain better understanding on laccase in apples and reveal its role in browning color formation during storage, laccases in apples were investigated. The full-length complementary DNAs encoding laccase genes were obtained from different tissues of apple including flowers, calyx, leaves and fruit peel of ‘Red Delicious’ and ‘Cortland’. The apple laccases were compared to those in other plant species and found to have up to 99% homology to Arabidopsis and litchi. qRT-PCR analysis revealed changes in transcript abundance of LAC genes (2, 7, 9, 12, 14, 15 and 16) during storage and in response to DPA and 1-MCP treatments. Enzyme activity of laccase protein in apple peel increased with storage in control fruit, while decreased significantly with DPA or 1-MCP. Changes in phenolic compounds in pericarp tissues decreased generally during storage, but no significant effect of DPA and 1-MCP treatments on the phenolic compounds was found. [ABSTRACT FROM AUTHOR]

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. • Upper thermal limit varies with heating rate in snail Batillaria attramentaria. • Critical temperature at which heart rate precipitously declines is higher in dark shell snails than light shell snails. • It's important to have thorough knowledge on heating rate in the field to obtain accurate upper thermal limit of gastropods. • Both heating rate and shell colour should be considered to understand the responses of gastropods to climate change. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Phospholipids are important biomolecules with strong self-assembling ability to form biomembranes or liposomes. However, biomimetic prodrugs of phospholipids are not well known, including their self-assembling behavior at the air/water interface or in aqueous media. Here we design and prepare a biomimetic phospholipid-like amphiphilic prodrug, 1- O -octodecyl-2-conjugated linoleoyl- sn -glycero-3-phosphatidyl gemcitabine (OLGPG). After spreading at the air/water interface, it formed Langmuir monolayers. Stable nanoassemblies were obtained based on molecular self-assembly after OLGPG was injected in water. An amphiphilic long-chained lipid, cholesteryl hemisuccinate polyethylene glycol 1500 (CHS-PEG) was mixed in the OLGPG Langmuir monolayers and nanoassemblies with the optimal proportion. The OLGPG and OLGPG/CHS-PEG nanoassemblies were spherical vesicles due to the hydrophobic interaction of lipid moieties with the small sizes of 50.33 nm and 64.76 nm, respectively. Phospholipase A 2 (PLA 2 ) is highly expressed in tumor tissues to specifically degrade the 2-acyl of phospholipid to lysophospholipid. OLGPG showed PLA 2 -sensitive degradation. The nanoassemblies showed higher in vitro anticancer effect on HepG2 cells than the parent drug gemcitabine. In the in vivo studies on the hepatocellular tumor-bearing mouse model, the OLGPG/CHS-PEG nanoassemblies group (eq. to 1/5 dose of the Gem group) showed the highest antitumor and tumor targeting effects compared to the other groups. The long-circulating phospholipid-like prodrug nanoassemblies are the promising anticancer nanomedicines based on the biomimetic strategy and specific tumor microenvironment. [ABSTRACT FROM AUTHOR]

Purification of total flavonoids from Ginkgo biloba flowers (GBF) extracts were studied using six resins. Adsorption-desorption experiments indicated that polyamide resin is the most suitable resin. The optimal purification process of total flavonoids of GBF was as follows: a loading concentration of 5.85 mg/mL, a loading volume of 1 bed volume (BV), a loading flow rate of 2 BV/h, a water volume of 2.67 BV, and a desorption solution of 40% ethanol. Under these conditions, the maximum purity of total flavonoids was 37.1 ± 1.1%. The antioxidant activity of purified flavonoids was further evaluated in vitro. It showed that the 40% ethanol purified fraction (Fr. B) group had the strongest antioxidant activity of the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity concentration for 50% of maximal effect (EC50, 145.4 ± 13.8 µg/mL) and ferric reducing ability (2.5 ± 0.2 mM FeSO4 equivalent mg−1 Fr. B). In addition, at the concentration of 160 µg/mL, the Fr. B strikingly increased the viability rate of hydrogen peroxide stimulated PC-12 cells to normal levels (***p < 0.001). This method provides a basis for the application and development of GBF resources. It indicated that the purified GBF flavonoids can be used as a source of potential antioxidant. [ABSTRACT FROM AUTHOR]

Head-mounted medical devices (HMDs) are disruptive inventions representing laboratories and clinical institutions worldwide are climbing the apexes of brain science. These complex devices are inextricably linked with a wide range knowledge containing the Physics, Imaging, Biomedical engineering, Biology and Pharmacology, particularly could be specifically designed for individuals, and finally exerting integrated bio-effect. The salient characteristics of them are non-invasive intervening in human brain's physiological structures, and alterating the biological process, such as thermal ablating the tumor, opening the BBB to deliver drugs and neuromodulating to enhance cognitive performance or manipulate prosthetic. The increasing demand and universally accepted of them have set off a dramatic upsurge in HMDs' studies, seminal applications of them span from clinical use to psychiatric disorders and neurological modulation. With subsequent pre-clinical studies and human trials emerging, the mechanisms of transcranial stimulation methods of them were widely studied, and could be basically came down to three notable approach: magnetic, electrical and ultrasonic stimulation. This review provides a comprehensive overviews of their stimulating mechanisms, and recent advances in clinic and military. We described the potential impact of HMDs on brain science, and current challenges to extensively adopt them as promising alternative treating tools. [Display omitted] [ABSTRACT FROM AUTHOR]

Sodium alginate and chitosan were in favor of wound healing. However, the two polymers were not compatible in one formulation due to the electrostatic interaction. Coaxially electrospinning technology could make two or more noneletrospun polymers to be electrospun in independent core and shell layer. Asiaticoside-loaded coaxially electrospinning nanofibers of alginate, polyvinyl alcohol (PVA) and chitosan (alginate/PVA/chitosan) were prepared and evaluated. Morphologies and microstructure of nanofibers were observed with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Drug release in vitro of coaxial nanofibers was also evaluated. Deep partial-thickness burn injury were established and used to evaluate the improved healing effect of asiaticoside-loaded coaxial nanofibers. Drug-loaded coaxial nanofibers prepared with the optimized formulations and technologies had the obvious core-shell structure. Coaxial nanofibers showed faster drug release profiles in vitro and this facilitated wound healing. Its healing effect on rats with deep partial-thickness burn injury was also significant based on morphology, wound healing ratio, and pathological sections. Positive expression of vascular endothelial growth factor (VEGF), cluster of differentiation 31 (CD31), and proliferating cell nuclear antigen (PCNA), and down regulation of tumor necrosis factor (TNF) and interleukin-6 (IL-6) also validated the improved effect of wound healing. In general, the asiaticoside-loaded coaxial nanofibers had obvious core-shell structure with smooth surface and uniform diameter. Its healing effect on deep partial-thickness burn injury of rats was obvious. Asiaticoside-loaded coaxial nanofibers provide a novel promising option for treatment of deep partial-thickness burn injury. [ABSTRACT FROM AUTHOR]

The effects of ethylene and 1-methylcyclopropene (1-MCP) on apple fruit volatile biosynthesis and gene expression were investigated. Statistical analysis identified 17 genes that changed significantly in response to ethylene and 1-MCP treatments. Genes encoding branched-chain amino acid aminotransferase ( BCAT ), aromatic amino acid aminotransferase (ArAT) and amino acid decarboxylases ( AADC ) were up-regulated during ripening and further enhanced by ethylene treatment. Genes related to fatty acid synthesis and metabolism, including acyl-carrier-proteins ( ACPs ), malonyl-CoA:ACP transacylase ( MCAT ), acyl-ACP-desaturase ( ACPD ), lipoxygenase ( LOX ), hydroperoxide lyase ( HPL ), alcohol dehydrogenase (ADH), pyruvate decarboxylase (PDC2), β-oxidation, acyl-CoA synthetase (ACS), enoyl-CoA hydratase (ECHD), acyl-CoA dehydrogenase (ACAD), and alcohol acyltransferases (AATs) also increased during ripening and in response to ethylene treatment. Allene oxide synthase (AOS), alcohol dehydrogenase 1 (ADH1), 3-ketoacyl-CoA thiolase and branched-chain amino acid aminotransferase 2 (BCAT2) decreased in ethylene-treated fruit. Treatment with 1-MCP and ethylene generally produced opposite effects on related genes, which provides evidence that regulation of these genes is ethylene dependent. [ABSTRACT FROM AUTHOR]

Radiation-induced brain injury (RBI) is a common neurological disease caused by ionizing radiation (IR). Edaravone (EDA) is a free radical scavenger, has the potential to treat RBI. EDA loaded temperature-sensitive gels (TSGs) were prepared for subcutaneous injection to improve inconvenient administration of intravenous infusion. RBI mice model was established by irradiation of 60Co γ-ray on head. EDA TSGs could improve spontaneous behavior, learning and memory and anxiety of RBI mice by behavior tests, including the open field test, the novel object recognition test, the elevated plus maze test and the fear conditioning test. The therapeutic effects were enhanced with the assistance of ultrasound. Alleviative pathological changes, decreased the expression of Molondialdehyde (MDA) and Interleukin-6 (IL-6) in the hippocampus of brain, indicated reduced oxidative stress and inflammatory response with the treatment of EDA TSGs and ultrasound. Moreover, ultrasound was superior to the use of EDA TSGs. Safe and effective EDA TSGs were prepared for RBI, and the feasibility of brain-targeted drug delivery enhanced by ultrasound was preliminarily demonstrated in this study. [ABSTRACT FROM AUTHOR]

Increased autophagy/mitophagy is thought to contribute to cerebellar dysfunction in Purkinje cell degeneration mice. Intriguingly, cerebellar Purkinje cells are highly vulnerable to hypoxia–ischemia (HI), related at least in part to their high metabolic activity. Whether or not excessive or supraphysiologic autophagy plays a role in Purkinje cell susceptibility to HI is unknown. Accordingly, we evaluated the role of autophagy in the cerebellum after global ischemia produced by asphyxial cardiac arrest in postnatal day (PND) 16–18 rats, using siRNA-targeted inhibition of Atg7, necessary for microtubule-associated protein light chain 3-II (LC3-II) and Atg12–Atg5 complex formation. Two days before a 9 min asphyxial cardiac arrest or sham surgery, Atg7 or control siRNA was injected intracisternally to target the cerebellum. Treatment with Atg7 siRNA: 1) reduced Atg7 protein expression in the cerebellum by 56%; 2) prevented the typical ischemia-induced formation of LC3-II in the cerebellum 24 h after asphyxial cardiac arrest; 3) improved performance on the beam-balance apparatus on days 1–5; and 4) increased calbindin-labeled Purkinje cell survival assessed on day 14. Improved Purkinje cell survival was more consistent in female vs. male rats, and improved beam-balance performance was only seen in female rats. Similar responses to Atg7 siRNA i.e. reduced autophagy and neurodegeneration vs. control siRNA were seen when exposing sex-segregated green fluorescent protein-LC3 tagged mouse primary cortical neurons to oxygen glucose deprivation in vitro. Thus, inhibition of autophagy after global ischemia in PND 16–18 rats leads to increased survival of Purkinje cells and improved motor performance in a sex-dependent manner. [ABSTRACT FROM AUTHOR]

Simple Summary: The Guangxi Zhuang Autonomous Region has one of the most abundant aquatic biodiversity in China, and it is a hotspot of global biodiversity research. In the present study, we explored the diversity, distribution, and biogeography of freshwater fishes in Guangxi. Our results showed that 380 species of freshwater fishes were recorded in Guangxi; the species diversity from northwest to southeast gradually decreased for most Sub−basins; the spatial turnover component was the main contributor to beta diversity; the freshwater fish system belonged to the South China division in the Southeast Asiatic subregion of the Oriental region. The Guangxi Zhuang Autonomous Region has the largest number of cavefish species in the world and is a global biodiversity hotspot. In this study, a species list of freshwater fishes in 12 Sub−basins of Guangxi was compiled systematically. Moreover, the species composition and distribution of the diversity were analyzed via the G-F index, taxonomic diversity index, and beta diversity index. Results showed that 380 species of freshwater fishes were recorded in this region, which belonged to 158 genera in 43 families and 17 orders in 2 phyla, in which 128 species of endemic fishes and 83 species of cavefish accounted for 33.68% and 21.84%, respectively. The species diversity from northwest to southeast gradually decreased for most Sub−basins. The G-F index has generally risen in recent years. The taxonomic diversity index showed that the freshwater fish taxonomic composition in Guangxi is uneven. The spatial turnover component was the main contributor to beta diversity. A cluster analysis showed that the 12 Sub−basins in the study area could be divided into four groups, and the phylogenetic relationships of freshwater fishes in Guangxi generally reflect the connections between water systems and geological history. The freshwater fish system in Guangxi, which belonged to the South China division in the Southeast Asiatic subregion of the Oriental region, originated in the early Tertiary period. The results will provide the information needed for freshwater fish resource protection in Guangxi and a reference for promoting the normalization of fish diversity conservation in the Pearl River Basin and other basins. [ABSTRACT FROM AUTHOR]