Effects of Compound Fertilizer and Branch Fertilizer on Population Construction and Yield of Machine-Transplanted Rice.

In order to study the effects of combined application of compound fertilizer and branch fertilizer on the growth and yield of machine-transplanted rice, four hybrid rice varieties were used as experimental materials, and four fertilization treatments were set up by completely random design: compound fertilizer (T0), compound fertilizer + conventional branch fertilizer (T1), compound fertilizer + (branch fertilizer - 20%) (T2), compound fertilizer + (branch fertilizer + 20%) (T3). The results showed that the branch fertilizer could effectively promote the early growth and rapid development of tillers, and increase the agronomic traits such as chlorophyll content, LAI and dry matter accumulation. Among the four varieties, the yield of the V4 variety was the highest under T3 treatment, which was 11,471.15 kg·hm-2, which was 37.34% higher than that of the control, and the yield increase effect was the most significant. The correlations showed that dry matter accumulation and LAI were significantly or highly significantly positively correlated with the number of effective spikes and yield, and the number of effective spikes was highly significantly positively correlated with the yield. In general, the application of pitchfork fertiliser increased the effective number of spikes and the number of grains per spike of each variety to different degrees, which effectively promoted the improvement of the rice yield.

Clinical profiles and related factors in tuberculosis patients with positive sputum smear mycobacterium tuberculosis tests.

The aim of this study was to explore the related factors linked to the development and infectivity of tuberculosis. This was achieved by comparing the clinical characteristics of patients with pulmonary tuberculosis (TB) who tested positive in smear Mycobacterium tuberculosis tests with this who tested negative in smear mycobacterium tests but positive in sputum Gene Xpert tests. We gathered clinical data of 1612 recently hospitalized patients diagnosed with pulmonary tuberculosis who tested positive either in sputum Gene-Xpert test or sputum smear Mycobacterium tuberculosis tests. The data was collected from January 1, 2018 to August 5, 2023, at Sichuan Provincial People's Hospital. We conducted separately analyzes and comparisons of the clinical characteristics between the two groups of patients, aiming to discussed the related factors influencing the development and infectivity of tuberculosis. In comparison to the GeneXpert positive group, the sputum smear positive group exhibited a higher proportion of elderly patients (aged 75-89) and individuals classified as underweight (BMI < 18.5 kg/m2). Furthermore, this group was more prone to experiencing symptoms such as weight loss, coughing and sputum production, hemoptysis, shortness of breath, and difficulty breathing. Moreover, they are also more likely to develop extrapulmonary tuberculosis, such as tuberculous meningitis, tuberculous pleurisy, and tuberculous peritonitis. These clinical features, when present, not only increase the likelihood of a positive result in sputum smear tests but also suggest a high infectivity of pulmonary tuberculosis. Elderly individuals (aged 75 to 89) who are underweight (BMI < 18.5 kg/m2), display symptom of cough, expectoration, hemoptysis and dyspnea-particularly cough and expectoration-and those with extra pulmonary tuberculosis serve as indicators of highly infectious pulmonary tuberculosis patients. These patients may present with more severe condition, carrying a higher bacteria, and being more prone to bacterial elimination. Identification of these patients is crucial, and prompt actions such as timely and rapid isolation measures, cutting off transmission routes, and early empirical treatment of tuberculosis are essential to control the development of the disease.

Synthesis, evaluation and structure-activity relationship studies of pterodontic acid acylated derivatives with anti-flu A virus (H1N1) activity in vitro.

In order to develop antiviral drugs, we utilized pterodontic acid (Poa-1) as a lead compound and conducted various modifications, including oxidation, reduction, addition, esterification, and acylation, resulting in the synthesis of 29 derivatives, of which 25 were novel acylation derivatives. Cell-level validation demonstrated that 4 derivatives exhibited significant inhibitory effects on the influenza A virus (H1N1), with an IC50 = 4.04-36.13 µM. Notably, four acylation derivatives (compounds IIE5, IIE6, IIE9, and IIE17) exhibited specific antiviral activities against influenza A virus (H1N1) with low cytotoxicity, indicating favorable therapeutic indices (SI = 3.5-11.9). Structure-activity relationship studies indicated that C5-C6 olefins are essential groups for antiviral activity, C11-C12 conjugated olefins will not interfere with antiviral activity. Carboxylic acid is an essential group for activity. Moreover，Carboxylic acid acylation can improve antiviral activity, and the inclusion of guanidine, cyclic amine, and phenyl groups with electron-donating substituents could enhance the antiviral activity of the lead compound. Natural products structural modifications are capable of improving the biological activity of lead compounds, offering a rapid pathway for the development of potent new structures.

Application of flow-through flaps for replantation after traumatic limb amputation according to the angiosome concept.

OBJECTIVE: This study was performed to explore the treatment of the injury caused by traumatic limb amputation. METHODS: From October 2002 to October 2021, 30 cases were enrolled in the present study. The reasons for injury were as follows: 8 cases with single hydraulic column crush injury, 12 cases with gear and wire rope stranding, 6 cases with belt avulsion injury, and 4 cases with carbon block smash injury. The present study application of a free or small saphenous vein bypass to reconstruct the injured artery and vein according to the concept of the angiosome model. The defective vessels were bridged with the axial vessels of a flow-through flap, such as a medial calf flap or anterolateral femoral flap, to construct an additional blood supply and drainage vein for the severed limb. The clinical data of 30 cases with traumatic limb amputation of the lower leg and ankle were retrospectively analyzed. RESULTS: In all 30 cases of traumatic limb amputation, the replantation via the adoption of a flow-through flap was successful, and 85.6% of the patients remained in good postoperative condition. There were no symptoms of ischemia in the marginal segment after blood supply reconstruction of the transected limb by axial vascular bridging within the flap. CONCLUSION: Via the adoption of microsurgical techniques, the blood supply to the transected limb can be reconstructed by bridging the defective vessels with the adoption of the axial vessels of the flow-through flap is a feasible and advanced treatment option.

LC/MS-guided isolation and GNPS procedures to identify flavonoid of HCoV-OC43 inhibitors.

The screening of based target compounds supported by LC/MS, MS/MS and Global Natural Products Social (GNPS) used to identify the compounds 1-10 of Butea monsperma. They were evaluated in human malignant embryonic rhabdomyoma cells (RD cells) infected with Human coronavirus OC43 (HCoV-OC43) and showed significant inhibitory activity. Target inhibition tests showed that compounds 6 and 8 inhibited the proteolytic enzyme 3CLpro, which is widely present in coronavirus and plays an important role in the replication process, with an effective IC50 value. The study confirmed that dioxymethylene of compound 8 may be a key active fragment in inhibiting coronavirus (EC50 7.2 µM, SI > 139.1). The results have led to identifying natural bioactive compounds for possible inhibiting HCoV-OC43 and developing drug for Traditional Chinese Medicine (TCM).

Impacts of longitudinal water curtain cooling system on transcriptome-related immunity in ducks.

BACKGROUND: The closed poultry houses integrated with a longitudinal water curtain cooling system (LWCCS) are widely used in modern poultry production. This study showed the variations in environmental conditions in closed houses integrated with a longitudinal water curtain cooling system. We evaluated the influence of different environmental conditions on duck growth performance and the transcriptome changes of immune organs, including the bursa of Fabricius and the spleen. RESULT: This study investigated the slaughter indicators and immune organ transcriptomes of 52-day-old Cherry Valley ducks by analyzing the LWCC at different locations (water curtain end, middle position, and fan cooling end). The results showed that the cooling effect of the LWCCS was more evident from 10:00 a.m. -14:00. And from the water curtain end to the fan cooling end, the hourly average temperature differently decreased by 0.310℃, 0.450℃, 0.480℃, 0.520℃, and 0.410℃, respectively (P < 0.05). The daily and hourly average relative humidity decreased from the water curtain end to the fan cooling end, dropping by 7.500% and 8.200%, respectively (P < 0.01). We also observed differences in production performance, such as dressing weight, half-eviscerated weight, skin fat rate, and percentage of abdominal fat (P < 0.01), which may have been caused by environmental conditions. RNA-sequencing (RNA-seq) revealed 211 and 279 differentially expressed genes (DEGs) in the ducks' bursa of Fabricius and spleen compared between the water curtain end and fan cooling end, respectively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the two organs showed the DEGs were mainly enriched in cytokine-cytokine receptor interaction, integral component of membrane, Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) signaling pathway, etc. Our results implied that full-closed poultry houses integrated with LWCCS could potentially alter micro-environments (water curtain vs. fan cooling), resulting in ducks experiencing various stressful situations that eventually affect their immunity and production performance. CONCLUSION: In this study, our results indicated that uneven distributions of longitudinal environmental factors caused by LWCCS would affect the dressed weight, breast muscle weight, skin fat rate, and other product performance. Moreover, the expression of immune-related genes in the spleen and bursa of ducks could be affected by the LWCCS. This provides a new reference to optimize the use of LWCCS in conjunction with close duck houses in practical production.

Diarylheptanoids with neuroprotective effects from Alpinia officinarum rhizomes.

Forty-three diarylheptanoids were isolated from Alpinia officinarum rhizomes among them eight ones (1-6) were undescribed compounds whose structures were identified by UV, IR, HRESIMS, and NMR. The neuroprotective effects of these diarylheptanoids were evaluated on H2O2-damaged SH-SY5Y cells. Compounds 7, 10, 12, 20, 22, 25, 28, 33, 35, 37, and 42 presented significant neuroprotective effects than that of the positive control (EGCG) at the concentrations of 5, 10 or 20 µM. Compounds 10, 22, 25, and 33 significantly reduced the ROS levels and inhibited the generations of MDA and NO in oxidative injured cells to display neuroprotective effects. This study lay the foundation for the application of Alpinia officinarum rhizomes.

Abietane diterpenoids with anti-neuroinflammation activity from Rosmarinus officinalis.

A total of 12 abietane diterpenoids were isolated and identified from Rosmarinus officinalis in which 6 ones were undescribed compounds. Their structures were illuminated by the HRESIMS, NMR, and ECD methods and named as rosmarinusin Q-V (1-6). It worthy mentioned that rosmarinusin Q was a novel abietane diterpenoid with 6/6/5 skeleton whose C ring was an α,ß-unsaturated five-element ketone. All the compounds and four compounds (13-16) reported in our previous paper were evaluated their anti-neuroinflammatory activities on the LPS-induced BV2 cells. Compounds 5, 8, 9, 11, and 15 displayed significant anti-neuroinflammatory activity at the concentration of 10, 20, and 40 µM respectively. These results confirmed that R. officinalis contained abundant abietane diterpenoids and these compounds showed potential values of anti-neuroinflammation which could be developed as neuroprotective agents for the treatment of nerve damage caused by inflammation.

An in situ forming gel co-loaded with pirarubicin and celecoxib inhibits postoperative recurrence and metastasis of breast cancer.

Surgical removal combined with postoperative chemotherapy is still the mainstay of treatment for most solid tumors. Although chemotherapy reduces the risk of recurrence and metastasis after surgery, it may produce serious adverse effects and impair patient compliance. In situ drug delivery systems are promising tools for postoperative cancer treatment, improving drug delivery efficiency and reducing side effects. Herein, an injectable phospholipid-based in situ forming gel (IPG) was prepared for the co-delivery of antitumor agent pirarubicin (THP) and cyclooxygenase-2 (COX-2) inhibitor celecoxib (CXB) in the surgical incision, and the latter are used extensively in adjuvant chemotherapy for cancer. After injection, the IPG co-loaded with THP and CXB (THP-CXB-IPG) underwent spontaneous phase transition and formed a drug reservoir that fitted the irregular surgical incisions perfectly. In vitro drug release studies and in vivo pharmacokinetic analysis had demonstrated the sustained release behaviors of THP-CXB-IPG. The in vivo therapeutic efficacy was evaluated in mice that had undergone surgical resection of breast cancer, and the THP-CXB-IPG showed considerable inhibition of residual tumor growth after surgery and reduced the incidence of pulmonary metastasis. Moreover, it reduced the systemic toxicity of chemotherapeutic agents. Therefore, THP-CXB-IPG can be a promising candidate for preventing postoperative recurrence and metastasis.

Aralianudaside A, an unusual skeleton triterpenoid saponin with anti-airway inflammatory activity from Aralia elata.

Aralianudaside A, a triterpene saponin with an unusual skeleton of pentacyclic triterpenoid, along with a new triterpene glycoside and six known compounds were obtained from the buds of Aralia elata. Their structures were determined through extensive spectral analysis, including HRESIMS, IR, 1D and 2D NMR, glycolysis and GC. All compounds were evaluated for anti-airway inflammatory activity in lipopolysaccharides (LPS)-induced airway epithelial cells (16HBE), compounds 1, 3, 5, 7 and 8 significantly decreased the expression of pro-inflammatory cytokines IL-1ß and IL-4.

Hypoxia-Responsive Golgi-Targeted Prodrug Assembled with Anthracycline for Improved Antitumor and Antimetastasis Efficacy.

Tumor metastasis is an intricate multistep process regulated via various proteins and enzymes modified and secreted by swollen Golgi apparatus in tumor cells. Thus, Golgi complex is considered as an important target for the remedy of metastasis. Currently, Golgi targeting technologies are mostly employed in Golgi-specific fluorescent probes for diagnosis, but their applications in therapy are rarely reported. Herein, we proposed a prodrug (INR) that can target and destroy the Golgi apparatus, which consisted of indomethacin (IMC) as the Golgi targeting moiety and retinoic acid (RA), a Golgi disrupting agent. The linker between IMC and RA was designed as a hypoxia-responsive nitroaromatic structure, which ensured the release of the prototype drugs in the hypoxic tumor microenvironment. Furthermore, INR could be assembled with pirarubicin (THP), an anthracycline, to form a carrier-free nanoparticle (NP) by emulsion-solvent evaporation method. A small amount of mPEG2000-DSPE was added to shield the positive charges and improve the stability of the nanoparticle to obtain PEG-modified nanoparticle (PNP). It was proved that INR released the prototype drugs in tumor cells and hypoxia promoted the release. The Golgi destructive effect of RA in INR was amplified owing to the Golgi targeting ability of IMC, and IMC also inhibited the protumor COX-2/PGE2 signaling. Finally, PNP exhibited excellent curative efficacy on 4T1 primary tumor and its pulmonary and hepatic metastasis. The small molecular therapeutic prodrug targeting Golgi apparatus could be adapted to multifarious drug delivery systems and disease models, which expanded the application of Golgi targeting tactics in disease treatment.

Effects of Low Light after Heading on the Yield of Direct Seeding Rice and Its Physiological Response Mechanism.

As a photophilous plant, rice is susceptible to low-light stress during its growth. The Sichuan Basin is a typical low-light rice-producing area. In this study, eight rice varieties with different shade tolerances were studied from 2021 to 2022. The physiological adaptability and yield formation characteristics of rice were studied with respect to photosynthetic physiological characteristics and dry matter accumulation characteristics, and the response mechanism of rice to low light stress was revealed. The results showed that the shading treatment significantly increased the chlorophyll a, chlorophyll b, and total chlorophyll contents in the leaves of direct-seeded rice after heading, and the total chlorophyll content increased by 1.68-29.70%. Nitrate reductase (NR) activity first increased and then decreased under each treatment, and the shading treatment reduced the NR activity of direct-seeded rice. Compared to the control treatment, the peroxidase (POD) activity of each variety increased from 7 to 24 d after the shading treatment. The transketolase (TK) activity in direct-seeded hybrid rice increased under low light stress. Compared with the control, shading treatment significantly reduced the aboveground dry matter, grain number per panicle, and seed setting rate of direct-seeded rice at the full heading stage and maturity stage, thus reducing the yield of direct-seeded rice by 26.10-34.11%. However, under the shading treatment, Zhenliangyou 2018 and Jingliangyou 534 maintained higher chlorophyll content and related enzyme activities, accumulated more photosynthetic products, and reduced yield. In general, Zhenliangyou 2018 and Jingliangyou 534 still had a yield of 7.06-8.33 t·hm-2 under low light. It indicated that Zhenliangyou 2018 and Jingliangyou 534 had better stability and stronger tolerance to weak light stress and had a higher yield potential in weak light areas such as Sichuan.

Computed Tomography Manifestations in Patients with Rifampin Primary Drug-Resistant Tuberculosis in an Infectious Disease Hospital in the Yi Autonomous Prefecture, China.

Purpose: This study aimed to investigate clinical features and computed tomography (CT) manifestations of rifampicin primary drug-resistant pulmonary tuberculosis in Liangshan Yi Autonomous Prefecture. Patients and Methods: A total of 100 inpatients with confirmed primary rifampicin-resistant pulmonary tuberculosis were recruited from January 2020 to December 2022 at an infectious disease hospital located in the Liangshan Yi Autonomous Prefecture. Additionally, 100 inpatients with confirmed drug-susceptible pulmonary tuberculosis during the same period were matched to the rifampicin-resistant group based on gender, age, and ethnicity. The clinical characteristics of the two groups were recorded separately. Furthermore, the CT manifestations in these patients were independently analyzed by three radiologists. Results: The results showed that comorbid diabetes mellitus was more prevalent in the drug-resistant tuberculosis (DR-TB) group than in the drug-susceptible tuberculosis (DS-TB) group (9% vs 0%, p=0.0032). In terms of imaging presentation, DR-TB patients exhibited a higher frequency of calcifications (55% vs 35.00%, p=0.0068), greater median number of cavities (5 vs 2, p=0.0027), and larger maximum cavity diameter (52.08±25.55 mm vs 42.72±17.48 mm, p=0.0097). Additionally, bilateral involvement was more common in DR-TB patients at the site of the lesion (89% vs 76%, p=0.0246), with a higher prevalence in the right middle (82% vs 68%, p=0.0332), right lower (82% vs 68%, p=0.0332), left upper (91% vs 77%, p=0.0113), and left lower lobes (92% vs 66%, p<0.0001). Conversely, the involvement of only one lobe was less frequent in patients with DR-TB than in those with DS-TB (4% vs 13%, p=0.0398), whereas the involvement of all five lobes was more common (68% vs 51%, p=0.0209). Conclusion: Patients with DR-TB exhibit a higher prevalence of severe imaging manifestations, highlighting the importance of CT in the early detection and diagnosis of DR-TB.

High-Fat Mouse Model to Explore the Relationship between Abnormal Lipid Metabolism and Enolase in Pancreatic Cancer.

Malignant tumors have become a major social health problem that seriously threatens human health, among which pancreatic cancer has a high degree of malignancy, difficult diagnosis and treatment, short survival time, and high mortality. More and more attention has been paid to abnormal lipid metabolism as a momentous carcinogenesis mechanism. Here, we explored the relationship between abnormal lipid metabolism, enolase, and pancreatic cancer by clinical data analysis. A high-fat mouse model was constructed, and then, a subcutaneous tumorigenesis mouse model of carcinoma of pancreatic cells and a metastatic neoplasm mouse pattern of pancreatic carcinoma cells injected through the tail vein were constructed to explore whether abnormal lipid metabolism affects the progression of pancreatic cancer in mice. We constructed a high-lipid model of pancreatic carcinoma cell lines and knockdown and overexpressed enolase in pancreatic carcinoma cell lines and investigated whether high lipid regulates epithelial-mesenchymal transition (EMT) by upregulating enolase (ENO), thereby promoting the cells of pancreatic carcinoma to invade and migrate. Triglycerides, total cholesterol, free cholesterin, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and neuron-specific enolase (NSE) from pancreatic cancer patients and nonpancreatic cancer patients were tested. The differences in blood lipids between patients with and without pancreatic carcinoma were compared, and the correlation between blood lipids and neuron-specific enolase was analyzed. We confirmed that the serum triglyceride level of pancreatic cancer patients at initial diagnosis is overtopping nonpancreatic cancer patients, and the neuron-specific enolase level of patients with pancreatic carcinoma is better than nonpancreatic carcinoma sufferers. Triglyceride level is positively correlated with neuron-specific enolase level, and serum triglyceride level has predictive value for pancreatic cancer. Hyperlipidemia can promote tumor growth and increase the expression levels of ENO1, ENO2, and ENO3 in subcutaneous tumor formation of pancreatic cancer in mice. Additional hyperlipidemia promoted pancreatic carcinoma metastasis in the lung in mice injected through the tail vein, which confirmed that hyperlipidemia accelerated the process of EMT by increasing the expression of ENO1, ENO2, and ENO3, therefore promoting the pancreatic cancer cell metastasis.

Spirooxindol alkaloids from Voacanga africana: Targeting biofilm of MBLs producing Escherichia coli.

Seven rarely spirooxindole alkaloids, voagafricines A-G (1-7) were isolated from the stem barks of Voacanga africana. Their structures were unambiguously elucidated by comprehensive spectroscopic data and electronic circular dichroism (ECD) analyses. 1 and 2 possess a unique indoleone system in conjugation with a 3,4'-decahydroquinoline spiral ring originating from seco-quinolhiddin core of the precursor, furthermore 1 undergo decarburization formed a novel C-3-nor monoterpenoid indole. All isolates were evaluated for their antibacterial activities against MBLs producing Escherichia coli strains. Compounds 1 and 7 were found to be potent inhibitors against E. coli 298 and 140 by targeting biofilm. Possible interaction sites of 1 and 7 with biofilm were preliminarily explored by means of molecular docking.

Computed tomography findings in patients with pulmonary tuberculosis and diabetes at an infectious disease hospital in China: a retrospective cross-sectional study.

BACKGROUND: This study aimed to investigate the relationship between active pulmonary tuberculosis (TB) and type 2 diabetes mellitus (T2DM) by analysing the clinical features and computed tomography (CT) findings of patients with active pulmonary TB and comorbid T2DM (TB-DM) in the LiangShan Yi regions. METHODS: We collected data from 154 hospitalised patients with TB-DM initially confirmed at an infectious disease hospital in the Liangshan Yi Autonomous Prefecture between 1 and 2019, and 31 December 2021. These were matched by sex and age ± 3 years to 145 hospitalised patients with initially confirmed pulmonary TB without comorbid T2DM (TB-NDM) over the same period. The clinical characteristics of the two groups were analysed separately. Three group-blinded radiologists independently analysed the CT findings and classified them into mild-to-moderate and severe groups. Severe chest CT lesion refers to a lesion that is less diffused or moderately dense and either exceeds the total volume of one lung, a high-density fused lesion greater than one-third of the volume of one lung, or a cavitary lesion with a maximum diameter ≥ 4 cm. RESULTS: No significant differences were observed in the presentation of clinical features. Regarding the severity of chest CT manifestation, patients with TB-DM had significantly more severe TB than those with TB-NDM (89.61% vs. 68.97%, P < 0.0001). Regarding CT findings, patients with TB-DM had higher proportions of consolidation (79.22% vs. 52.41%, P < 0.0001), cavitary lesions (85.06% vs. 59.31%, P < 0.0001), bronchiectasis (71.43% vs. 31.03%, P < 0.0001), exudative lesions (88.96% vs. 68.28%, P < 0.0001), and fibrous lesions (93.51% vs. 68.97%, P < 0.0001) than patients with TB-NDM. In conclusion, patients with TB-DM have more severe pulmonary TB CT findings than those without. There were no significant differences in the distribution of lesions in the lung lobes between TB-DM and TB-NDM patients. CONCLUSIONS: Among patients hospitalised with pulmonary TB, those with T2DM had more severe findings on chest CT than those without T2DM. However, the clinical presentation was not significantly different.

T817MA Regulates Mitochondrial Dynamics via Sirt1 and Arc Following Subarachnoid Hemorrhage.

Spontaneous subarachnoid hemorrhage (SAH) is an acute neurologic emergency with poor outcomes, and mitochondrial dysfunction is known as one of the key pathological mechanisms underlying the SAH-induced early brain injury (EBI). 1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl} azetidin-3-ol maleate (T817MA) is a newly synthesized neurotrophic compound that has been demonstrated to exert protective effects against brain injury. Here, we investigated the effect of T817MA in neuronal injury following experimental SAH both in vitro and in vivo. Primary cultured cortical neurons were treated with oxyhemoglobin (OxyHb) to mimic SAH in vitro, and T817MA at concentrations higher than 0.1 µM reduced OxyHb-induced neuronal injury. T817MA treatment significantly inhibited lipid peroxidation, reduced neuronal apoptosis and attenuated mitochondrial fragmentation. The results of western blot showed that T817MA markedly reduced the expression of mitochondrial fission proteins, fission protein 1 (Fis-1) and dynamin-related GTPase-1 (Drp-1), but prolonged the expression of the postsynaptic protein activity-regulated cytoskeleton-associated protein (Arc). In addition, T817MA significantly increased the expression of sirtuin 1 (Sirt1), which was accompanied by preserved enzymatic of isocitrate dehydrogenase (IDH2) and superoxide dismutase (SOD). Knockdown of Sirt1 and Arc via small interfere RNA (siRNA) transfection partially prevented the T817MA-induced protection in cortical neurons. Furthermore, treatment with T817MA in vivo significantly reduced brain damage and preserved neurological function in rats. The decreased expression of Fis-1 and Drp-1, as well as the increased expression of Arc and Sirt1 were also observed in vivo. Taken together, these data indicate that the neuroprotective agent T817MA protects against SAH-induced brain injury via Sirt1- and Arc-mediated regulation of mitochondrial dynamics.

A fibroblastic foci-targeting and hypoxia-cleavable delivery system of pirfenidone for the treatment of idiopathic pulmonary fibrosis.

The progressive formation of fibroblastic foci characterizes idiopathic pulmonary fibrosis (IPF), and excessive oral doses of approved pirfenidone (PFD) always cause gastrointestinal side effects. The fibrotic response driven by activated fibroblasts could perpetuate epithelial damage and promote abnormal extracellular matrix (ECM) deposition. When modified nanoparticles reach their target, it is important to ensure a responsive release of PFD. Hypoxia is a determining factor in IPF, leading to alveolar dysfunction and deeper cellular fibrosis. Herein, a fibroblastic foci-targeting and hypoxia-cleavable drug delivery system (Fn-Azo-BSA@PEG) was established to reprogram the fibrosis in IPF. We have modified the FnBAP5 peptide to enable comprehensive fibroblastic foci targeting, which helps BSA nanoparticles recognize and accumulate at fibrotic sites. Meantime, the hypoxia-responsive azobenzene group allowed for efficient and rapid drug diffusion, while the PEGylated BSA reduced system toxicity and increased circulation in vivo. As expected, the strategy of the fibronectin-targeting-modification and hypoxia-responsive drug release synergistically inhibited activated fibroblasts and reduced the secretion of the fibrosis-related protein. Fn-Azo-BSA@PEG could accumulate in pulmonary tissue and prolong the survival time in bleomycin-induced pulmonary fibrosis mice. Together, the multivalent BSA nanoparticles offered an efficient approach for improving lung architecture and function by regulating the fibroblastic foci and hypoxia. STATEMENT OF SIGNIFICANCE: We established fibroblastic foci-targeting and hypoxia-cleavable bovine serum albumin (BSA) nanoparticles (Fn-Azo-BSA@PEG) to reprogramme the fibroblastic foci in idiopathic pulmonary fibrosis (IPF). Fn-Azo-BSA@PEG was designed to actively target fibroblasts and abnormal ECM with the FnBPA5 peptide, delivering more FDA-approved pirfenidone (PFD) to the cross-talk within the foci. Once the drug reached fibroblastic foci, the azobenzene group acted as a hypoxia-responsive linker to trigger effective and rapid drug release. Hypoxic responsiveness and FnBAP5-modification of Fn-Azo-BSA@PEG synergistically inhibited the secretion of proteins closely related to fibrogenesis. BSA's inherent transport and metabolic pathways in the pulmonary reduced the side effects of the main organs. The multivalent BSA nanoparticles efficiently inhibited IPF-fibrosis progress and preserved the lung architecture by regulating the fibroblastic foci and hypoxia.

Scavenger receptor A-mediated nanoparticles target M1 macrophages for acute liver injury.

Acute liver injury (ALI) has an elevated fatality rate due to untimely and ineffective treatment. Although, schisandrin B (SchB) has been extensively used to treat diverse liver diseases, its therapeutic efficacy on ALI was limited due to its high hydrophobicity. Palmitic acid-modified serum albumin (PSA) is not only an effective carrier for hydrophobic drugs, but also has a superb targeting effect via scavenger receptor-A (SR-A) on the M1 macrophages, which are potential therapeutic targets for ALI. Compared with the common macrophage-targeted delivery systems, PSA enables site-specific drug delivery to reduce off-target toxicity. Herein, we prepared SchB-PSA nanoparticles and further assessed their therapeutic effect on ALI. In vitro, compared with human serum albumin encapsulated SchB nanoparticles (SchB-HSA NPs), the SchB-PSA NPs exhibited more potent cytotoxicity on lipopolysaccharide (LPS) stimulated Raw264.7 (LAR) cells, and LAR cells took up PSA NPs 8.79 times more than HSA NPs. As expected, the PSA NPs also accumulated more in the liver. Moreover, SchB-PSA NPs dramatically reduced the activation of NF-κB signaling, and significantly relieved inflammatory response and hepatic necrosis. Notably, the high dose of SchB-PSA NPs improved the survival rate in 72 h of ALI mice to 75%. Hence, SchB-PSA NPs are promising to treat ALI.

Effect of Sowing Date on the Growth Characteristics and Yield of Growth-Constrained Direct-Seeding Rice.

To investigate changes in the yield and physiological characteristics of indica hybrid rice varieties sown on different dates, we evaluated appropriate hybrid rice varieties and their optimal sowing dates in the hilly areas of Sichuan. Three popular indica rice varieties were used as experimental materials, and five sowing dates were set uniformly locally [16 May (SD1), 23 May (SD2), 30 May (SD3), 6 June (SD4), and 13 June (SD5)] to investigate differences in the yield characteristics, growth period, and dry matter accumulation. The results showed that, over the two years, the sowing-to-heading period and overall growth period of the three varieties shortened as the sowing date was delayed, and the difference in yield between the SD1 and SD2 treatments was not significant, owing to higher material accumulation after flowering and higher assimilative material transport capacity. These varieties are both photosensitive and tolerant to low temperatures. Among the three varieties tested, the Huangyouyuehesimiao (V3) cultivar had the highest yield, with 10.75 t ha-1 under the SD2 treatment. The impact of shifting the sowing date on yield components varied. Delaying the sowing date increased and then decreased the number of effective panicles, and the number of grains per panicle and the seed setting rate decreased by differing degrees. In summary, a high yield of indica hybrid rice can be maintained by sowing between 16 and 23 May each year in the study area. It indicated that indica hybrid rice in the hilly rice-producing region of Sichuan is highly adaptable to different sowing dates.