Synergistic role of phenylpropanoid biosynthesis and citrate cycle pathways in heavy metal detoxification through secretion of organic acids.

Excessive heavy metal contaminants in soils have serious ecological and environmental impacts, and affect plant growth and crop yields. Phytoremediation is an environmentally friendly means of lowering heavy metal concentrations in soils. In this study, we analyzed phenotypic and physiological traits, and the transcriptome and metabolome, of sheepgrass (Leymus chinensis) exposed to cadmium (Cd), lead (Pb), or zinc (Zn). Phenotypic and physiological analysis indicated that sheepgrass had strong tolerance to Cd/Pb/Zn. Transcriptomic analysis revealed that phenylpropanoid biosynthesis and organic acid metabolism were enriched among differentially expressed genes, and metabolomic analysis indicated that the citrate cycle was enriched in response to Cd/Pb/Zn exposure. Genes encoding enzymes involved in the phenylpropanoid and citrate cycle pathways were up-regulated under the Cd/Pb/Zn treatments. Organic acids significantly reduced heavy metal accumulation and improved sheepgrass tolerance of heavy metals. The results suggest that synergistic interaction of the phenylpropanoid and citrate cycle pathways in sheepgrass roots induced organic acid secretion to alleviate heavy metal toxicity. A cascade of enzymes involved in the interacting pathways could be targeted in molecular design breeding to enhance phytoremediation.

Microenvironment modulation of interpenetrating-type hierarchical porous foam carbon by mild-homogeneous activation for H2 storage and CO2 capture under ambient pressure.

Currently, carbon-based porous materials for hydrogen (H2) storage and carbon dioxide (CO2) capture are mostly applied at higher pressures (30-300 bar). However, applications for H2 storage and CO2 capture under ambient pressure conditions are significant for the development of portable, household, and miniaturized H2 energy technologies. This demands a higher standard for the interface microenvironment of adsorbents. Derived from polyurethane foams (PUFs) solid waste, the hierarchical porous foam carbon with interpenetrating-type pore structures exhibits high specific surface area (SBET = 1753 m2/g), abundant oxygen and nitrogen functional groups, and a hierarchical nanopore structure (VUltra = 0.232 cm3/g, VMicro = 0.628 cm3/g and VMeso = 0.186 cm3/g) through the mild-homogeneous sonication-assisted activation process. Under the limited adsorption of pore interface microenvironment composed by hierarchical nanopore structure and dipole-induced interaction (H(Ⅱ)-H(Ⅰ)···N/O and O(Ⅱ) = C(Ⅰ) = O(Ⅱ)···N/O), it exhibits an excellent H2 storage density (2.92 wt% at 77 K, 1 bar) and CO2 capture capacity (5.28 mmol/g at 298 K, 1 bar). This research approach can serve as a reference for the dual-functional design of porous foam carbon, and promote the development of adsorption materials for CO2 capture and energy gas storage under ambient conditions.

Finite element analysis of meniscus contact mechanical behavior based on kinematic simulation of abnormal gait.

The meniscus plays a crucial role in the proper functioning of the knee joint, and when it becomes damaged, partial removal or replacement is necessary to restore proper function. Understanding the stress and deformation of the meniscus during various movements is essential for developing effective materials for meniscus repair. However, accurately estimating the contact mechanics of the knee joint can be challenging due to its complex shape and the dynamic changes it undergoes during movement. To address this issue, the open-source software SCONE can be used to establish a kinematics model that monitors the different states of the knee joint during human motion and obtains relevant gait kinematics data. To evaluate the stress and deformation of the meniscus during normal human movement, values of different states in the movement gait can be selected for finite element analysis (FEA) of the knee joint. This analysis enables researchers to assess changes in the meniscus. To evaluate meniscus damage, it is necessary to obtain changes in its mechanical behavior during abnormal movements. This information can serve as a reference for designing and optimizing the mechanical performance of materials used in meniscus repair and replacement.

Anti-Melanogenic Effects of Takifugu flavidus Muscle Hydrolysate in B16F10 Melanoma Cells and Zebrafish.

Abnormal melanogenesis can lead to hyperpigmentation. Tyrosinase (TYR), a key rate-limiting enzyme in melanin production, is an important therapeutic target for these disorders. We investigated the TYR inhibitory activity of hydrolysates extracted from the muscle tissue of Takifugu flavidus (TFMH). We used computer-aided virtual screening to identify a novel peptide that potently inhibited melanin synthesis, simulated its binding mode to TYR, and evaluated functional efficacy in vitro and in vivo. TFMH inhibited the diphenolase activities of mTYR, reducing TYR substrate binding activity and effectively inhibiting melanin synthesis. TFMH indirectly reduced cAMP response element-binding protein phosphorylation in vitro by downregulating melanocortin 1 receptor expression, thereby inhibiting expression of the microphthalmia-associated transcription factor, further decreasing TYR, tyrosinase related protein 1, and dopachrome tautomerase expression and ultimately impeding melanin synthesis. In zebrafish, TFMH significantly reduced black spot formation. TFMH (200 µg/mL) decreased zebrafish TYR activity by 43% and melanin content by 52%. Molecular dynamics simulations over 100 ns revealed that the FGFRSP (T-6) peptide stably binds mushroom TYR via hydrogen bonds and ionic interactions. T-6 (400 µmol/L) reduced melanin content in B16F10 melanoma cells by 71% and TYR activity by 79%. In zebrafish, T-6 (200 µmol/L) inhibited melanin production by 64%. TFMH and T-6 exhibit good potential for the development of natural skin-whitening cosmetic products.

Stimuli-responsive microcarriers and their application in tissue repair: A review of magnetic and electroactive microcarrier.

Microcarrier applications have made great advances in tissue engineering in recent years, which can load cells, drugs, and bioactive factors. These microcarriers can be minimally injected into the defect to help reconstruct a good microenvironment for tissue repair. In order to achieve more ideal performance and face more complex tissue damage, an increasing amount of effort has been focused on microcarriers that can actively respond to external stimuli. These microcarriers have the functions of directional movement, targeted enrichment, material release control, and providing signals conducive to tissue repair. Given the high controllability and designability of magnetic and electroactive microcarriers, the research progress of these microcarriers is highlighted in this review. Their structure, function and applications, potential tissue repair mechanisms, and challenges are discussed. In summary, through the design with clinical translation ability, meaningful and comprehensive experimental characterization, and in-depth study and application of tissue repair mechanisms, stimuli-responsive microcarriers have great potential in tissue repair.

Injectable and in situ foaming shape-adaptive porous Bio-based polyurethane scaffold used for cartilage regeneration.

Irregular articular cartilage injury is a common type of joint trauma, often resulting from intense impacts and other factors that lead to irregularly shaped wounds, the limited regenerative capacity of cartilage and the mismatched shape of the scaffods have contributed to unsatisfactory therapeutic outcomes. While injectable materials are a traditional solution to adapt to irregular cartilage defects, they have limitations, and injectable materials often lack the porous microstructures favorable for the rapid proliferation of cartilage cells. In this study, an injectable porous polyurethane scaffold named PU-BDO-Gelatin-Foam (PUBGF) was prepared. After injection into cartilage defects, PUBGF forms in situ at the site of the defect and exhibits a dynamic microstructure during the initial two weeks. This dynamic microstructure endows the scaffold with the ability to retain substances within its interior, thereby enhancing its capacity to promote chondrogenesis. Furthermore, the chondral repair efficacy of PUBGF was validated by directly injecting it into rat articular cartilage injury sites. The injectable PUBGF scaffold demonstrates a superior potential for promoting the repair of cartilage defects when compared to traditional porous polyurethane scaffolds. The substance retention ability of this injectable porous scaffold makes it a promising option for clinical applications.

Generalizable transcriptome-based tumor malignant level evaluation and molecular subtyping towards precision oncology.

In cancer treatment, therapeutic strategies that integrate tumor-specific characteristics (i.e., precision oncology) are widely implemented to provide clinical benefits for cancer patients. Here, through in-depth integration of tumor transcriptome and patients' prognoses across cancers, we investigated dysregulated and prognosis-associated genes and catalogued such important genes in a cancer type-dependent manner. Utilizing the expression matrices of these genes, we built models to quantitatively evaluate the malignant levels of tumors across cancers, which could add value to the clinical staging system for improved prediction of patients' survival. Furthermore, we performed a transcriptome-based molecular subtyping on hepatocellular carcinoma, which revealed three subtypes with significantly diversified clinical outcomes, mutation landscapes, immune microenvironment, and dysregulated pathways. As tumor transcriptome was commonly profiled in clinical practice with low experimental complexity and cost, this work proposed easy-to-perform approaches for practical clinical promotion towards better healthcare and precision oncology of cancer patients.

Utilizing Group Model Building to Identify Barriers and Facilitators of Hypertension Management in Primary Health Care, China.

Purpose: Group Model Building (GMB) is a qualitative method that refers to a participatory process. This project aims to identify barriers and facilitators of hypertension management in primary health care in China, through which, the leverage point for intervention may be found. Methods: The GMB was used to identify the factors influencing hypertension management. Graphs over time and causal loop diagram (CLD) were main tools of GMB. To propose the influencing factors, key stakeholders were invited to participate in a workshop. During the workshop, stakeholders were encouraged to plot the graphs over time of the variables about research issues and give a descriptive explanation. And based on this, a CLD was initially developed to establish a model of the interaction of factors. After the workshop, the research group further improved the CLD through repeated mutual discussions, and gave feedback to the participants. The Vensim PLE 9.0 software package was used to build CLD. Results: A total of 14 key stakeholders were invited to participate in the workshop. Finally, 26 influencing factors were identified, which were divided into three dimensions, including the institutional, the community health workers (CHWs), and the patient level. And 5 reinforcing loops and 4 balancing loops were formed in the CLD. Promoting the building of the Medical Community/Regional Medical Association, implementing the family doctor contract service (FDCS), and enhancing the motivation of CHWs may be potential leverage points for hypertension management in China. Conclusion: By using GMB, we have identified key factors in the management of hypertension in primary health care and provided comprehensive suggestions to overcome the obstacles.

The prediction of pCR and chemosensitivity for breast cancer patients using DLG3, RADL and Pathomics signatures based on machine learning and deep learning.

BACKGROUND: Limited studies have investigated the predictive value of multiomics signatures (radiomics, deep learning features, pathological features and DLG3) in breast cancer patients who underwent neoadjuvant chemotherapy (NAC). However, no study has explored the relationships among radiomic, pathomic signatures and chemosensitivity. This study aimed to predict pathological complete response (pCR) using multiomics signatures, and to evaluate the predictive utility of radiomic and pathomic signatures for guiding chemotherapy selection. METHODS: The oncogenic function of DLG3 was explored in breast cancer cells via DLG3 knockdown. Immunohistochemistry (IHC) was used to evaluate the relationship between DLG3 expression and docetaxel/epirubin sensitivity. Machine learning (ML) and deep learning (DL) algorithms were used to develop multiomics signatures. Survival analysis was conducted by K-M curves and log-rank. Multivariate logistic regression analysis was used to develop nomograms. RESULTS: A total of 311 patients with malignant breast tumours who underwent NAC were retrospectively included in this multicentre study. Multiomics (DLG3, RADL and PATHO) signatures could accurately predict pCR (AUC: training: 0.900; testing: 0.814; external validation: 0.792). Its performance is also superior to that of clinical TNM staging and the single RADL signature in different cohorts. Patients in the low DLG3 group more easily achieved pCR, and those in the high RADL Signature_pCR and PATHO_Signature_pCR (OR = 7.93, 95 % CI: 3.49-18, P < 0.001) groups more easily achieved pCR. In the TEC regimen NAC group, patients who achieved pCR had a lower DLG3 score (4.00 ± 2.33 vs. 6.43 ± 3.01, P < 0.05). Patients in the low RADL_Signature_DLG3 and PATHO_Signature_DLG3 groups had lower DLG3 IHC scores (P < 0.05). Patients in the high RADL signature, PATHO signature and DLG3 signature groups had worse DFS and OS. CONCLUSIONS: Multiomics signatures (RADL, PATHO and DLG3) demonstrated great potential in predicting the pCR of breast cancer patients who underwent NAC. The RADL and PATHO signatures are associated with DLG3 status and could help doctors or patients choose proper neoadjuvant chemotherapy regimens (TEC regimens). This simple, structured, convenient and inexpensive multiomics model could help clinicians and patients make treatment decisions.

The Effects of Four Different Thawing Methods on Quality Indicators of Amphioctopus neglectus.

Amphioctopus neglectus is a species of octopus that is favored by consumers due to its rich nutrient profile. To investigate the influence of different thawing methods on the quality of octopus meat, we employed four distinct thawing methods: air thawing (AT), hydrostatic thawing (HT), flowing water thawing (FWT), and microwave thawing (MT). We then explored the differences in texture, color, water retention, pH, total volatile basic nitrogen (TVB-N), total sulfhydryl content, Ca2+-ATPase activity, and myofibrillar protein, among other quality indicators in response to these methods, and used a low-field nuclear magnetic resonance analyzer to assess the water migration that occurred during the thawing process. The results revealed that AT had the longest thawing time, leading to oxidation-induced protein denaturation, myofibrillar protein damage, and a significant decrease in water retention. Additionally, when this method was utilized, the content of TVB-N was significantly higher than in the other three groups. HT, to a certain extent, isolated the oxygen in the meat and thus alleviated protein oxidation, allowing higher levels of Ca2+-ATPase activity, sulfhydryl content, and springiness to be maintained. However, HT had a longer duration: 2.95 times that of FWT, resulting in a 9.84% higher cooking loss and a 28.21% higher TVB-N content compared to FWT. MT had the shortest thawing time, yielding the lowest content of TVB-N. However, uneven heating and in some cases overcooking occurred, severely damaging the protein structure, with a concurrent increase in thawing loss, W value, hardness, and shear force. Meanwhile, FWT improved the L*, W* and b* values of octopus meat, enhancing its color and water retention. The myofibrillar protein (MP) concentration was also the highest after FWT, with clearer subunit bands in SDS-PAGE electrophoresis, indicating that less degradation occurred and allowing greater springiness, increased Ca2+-ATPase activity, and a higher sulfhydryl content to be maintained. This suggests that FWT has an inhibitory effect on oxidation, alleviating protein oxidation degradation and preserving the quality of the meat. In conclusion, FWT outperformed the other three thawing methods, effectively minimizing adverse changes during thawing and successfully maintaining the quality of octopus meat.

A dual dynamically cross-linked hydrogel promotes rheumatoid arthritis repair through ROS initiative regulation and microenvironment modulation-independent triptolide release.

High oxidative stress and inflammatory cell infiltration are major causes of the persistent bone erosion and difficult tissue regeneration in rheumatoid arthritis (RA). Triptolide (TPL) has become a highly anticipated anti-rheumatic drug due to its excellent immunomodulatory and anti-inflammatory effects. However, the sudden drug accumulation caused by the binding of "stimulus-response" and "drug release" in a general smart delivery system is difficult to meet the shortcoming of extreme toxicity and the demand for long-term administration of TPL. Herein, we developed a dual dynamically cross-linked hydrogel (SPT@TPL), which demonstrated sensitive RA microenvironment regulation and microenvironment modulation-independent TPL release for 30 days. The abundant borate ester/tea polyphenol units in SPT@TPL possessed the capability to respond and regulate high reactive oxygen species (ROS) levels on-demand. Meanwhile, based on its dense dual crosslinked structure as well as the spontaneous healing behavior of numerous intermolecular hydrogen bonds formed after the breakage of borate ester, TPL could remain stable and slowly release under high ROS environments of RA, which dramatically reduced the risk of TPL exerting toxicity while maximized its long-term efficacy. Through the dual effects of ROS regulation and TPL sustained-release, SPT@TPL alleviated oxidative stress and reprogrammed macrophages into M2 phenotype, showing marked inhibition of inflammation and optimal regeneration of articular cartilage in RA rat model. In conclusion, this hydrogel platform with both microenvironment initiative regulation and TPL long-term sustained release provides a potential scheme for rheumatoid arthritis.

In Situ Synthesis of Self-Assembly Supramolecular Crystal Seeds within Continuous Carbon Nanofibers for Improved Fiber Graphitic Structure.

The utilization of carbon-based fibers as a fundamental constituent holds strong appeal for diverse materials and devices. However, the poor fiber graphitic structure resulting from the heat treatment of atactic polyacrylonitrile (PAN) precursors often leads to a modest performance of carbon-based fibers. This paper takes electrospun carbon nanofibers (CNFs) as the research object and provides a seed-assisted graphitization strategy to improve the fiber graphitic structures. The typical melamine/cyanuric acid self-assembly precursor of graphitic carbon nitride is applied as supramolecular seeds in CNFs and demonstrates significant promotion of fiber graphitization, while it decomposes at elevated temperatures. Further studies show that the higher carbon content contributes to the better heat resistance of seeds; thus, nanoscale 2,6-diaminopyridine/cyanuric acid and 2,4,6-triaminopyrimidine/barbituric acid supramolecular seeds are developed. Both systems can be uniformly distributed in PAN precursors through in situ self-assembly and withstand high-temperature carbonization without severe pyrolysis. The dispersed seeds contribute to the formation of fibrillar PAN crystals and promote their conversion to ordered graphitic domains through nucleation and templating roles. The obtained CNFs exhibit increased crystallinity and graphitization degree with improved orientation and refined size of fiber crystals. As a result, the strength, modulus, and elongation at break of CNFs are comprehensively enhanced.

Contribution of Immune Responses to the Cardiotoxicity and Hepatotoxicity of Deltamethrin in Early Life Stage Zebrafish (Danio rerio).

Deltamethrin (DM) is a widely used insecticide that has demonstrated developmental toxicity in the early life stages of fish. To better characterize the underlying mechanisms, embryos from Tg(cmlc2:RFP), Tg(apo14:GFP), and Tg(mpx:GFP) transgenic strains of zebrafish were exposed to nominal DM concentrations of 0.1, 1, 10, 25, and 50 µg/L until 120 h post-fertilization (hpf). Heart size increased 56.7%, and liver size was reduced by 17.1% in zebrafish exposed to 22.7 and 24.2 µg/L DM, respectively. RNA sequencing and bioinformatic analyses predicted that key biological processes affected by DM exposure were related to inflammatory responses. Expression of IL-1 protein was increased by 69.0% in the 24.4 µg/L DM treatment, and aggregation of neutrophils in cardiac and hepatic histologic sections was also observed. Coexposure to resatorvid, an anti-inflammatory agent, mitigated inflammatory responses and cardiac toxicity induced by DM and also restored liver biomass. Our data indicated a complex proinflammatory mechanism underlying DM-induced cardiotoxicity and hepatotoxicity which may be important for key events of adverse outcomes and associated risks of DM to early life stages of fish.

Identification of a novel inflammatory-related gene signature to evaluate the prognosis of gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is a highly aggressive malignancy with a heterogeneous nature, which makes prognosis prediction and treatment determination difficult. Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours. Inflammation also affects the prognosis of GC patients. Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis. However, the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear. AIM: To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients. METHODS: In this study, the mRNA expression profiles and corresponding clinical information of GC patients were obtained from the Gene Expression Omnibus (GEO) database (GSE66229). An inflammatory-related gene prognostic signature model was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database. GC patients from the GSE26253 cohort were used for validation. Univariate and multivariate Cox analyses were used to determine the independent prognostic factors, and a prognostic nomogram was established. The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram. The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram. Gene set enrichment analysis was performed to explore the potential regulatory pathways involved. The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT. Finally, we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents. RESULTS: A prognostic model consisting of three inflammatory-related genes (MRPS17, GUF1, and PDK4) was constructed. Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients. According to the risk score, GC patients were stratified into high- and low-risk groups, and patients in the high-risk group had significantly worse prognoses according to age, sex, TNM stage and Lauren type. Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging. Finally, the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group, indicating a link between inflammation-related genes and drug sensitivity. CONCLUSION: In conclusion, we established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.

Pulsatile Flow Increases METTL14-induced m6A modification and attenuates septic cardiomyopathy: an experimental study.

INTRODUCTION: Septic cardiomyopathy is a sepsis-mediated cardiovascular complication with severe microcirculatory malperfusion. Emerging evidence has highlighted the protective effects of pulsatile flow in case of microcirculatory disturbance, yet the underlying mechanisms are still elusive. The objective of this study was to investigate the mechanisms of N6-methyladenosine (m6A) modification in the alleviation of septic cardiomyopathy associated with extracorporeal membrane oxygenation (ECMO)-generated pulsatile flow. METHODS: Rat model with septic cardiomyopathy was established and was supported under ECMO either with pulsatile or non-pulsatile flow. Peripheral perfusion index (PPI) and cardiac function parameters were measured using ultrasonography. Dot blot assay was applied to examine the m6A level, while qRT-PCR, Western blot, immunofluorescence, and immunohistochemistry were used to measure the expressions of related genes. RNA immunoprecipitation assay was performed to validate the interaction between molecules. RESULTS: The ECMO-generated pulsatile flow significantly elevates microcirculatory PPI, improves myocardial function, protects the endothelium, and prolongs survival in rat models with septic cardiomyopathy. The pulsatile flow mediates the METTL14-mediated m6A modification to zonula occludens- (ZO-) 1 mRNA which stabilizes the ZO-1 mRNA depending on the presence of YTHDF2. The pulsatile flow suppresses the PI3K-Akt signaling pathway, of which the downstream molecule Foxo1, a negative transcription factor of METTL14, binds to the METTL14 promoter and inhibits the METTL14-induced m6A modification. CONCLUSION: The ECMO-generated pulsatile flow increases METTL14-induced m6A modification in ZO-1 and attenuates the progression of septic cardiomyopathy, suggesting that pulsatility might be a new therapeutic strategy in septic cardiomyopathy by alleviating microcirculatory disturbance.

Hispidulin targets PTGS2 to improve cyclophosphamide-induced cystitis by suppressing NLRP3 inflammasome.

Interstitial cystitis (IC) is a chronic bladder inflammation. Inhibition of prostaglandin G/H synthase 2 (PTGS2) is the most common method for controlling inflammation-related diseases. This study aimed to analyze the effects of hispidulin on the PTGS2 and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammation in experimental IC models. A binding activity between hispidulin and PTGS2 was measured using molecular docking. Human urothelial cells (SV-HUC-1) were stimulated by 2 ng/mL of interleukin (IL)-1ß for 24 h and cultured in a medium with different concentrations of hispidulin (2.5, 5, 10, 20 µM) for 24 h to observe the expressions of PTGS2 and NLRP3 protein. Cells overexpressing PTGS2 were established by PTGS2 cDNA transfection. In the IL-1ß-treated cells, the NLRP3 inflammasome was measured after 20 µM hispidulin treatment. In rats, animals were performed with three injections of 40 mg/kg cyclophosphamide (CYP) and orally treated with 50 mg/kg/day hispidulin or ibuprofen for 3 days. The bladder pain was measured using Von Frey filaments, and the bladder pathology was observed using hematoxylin and eosin (H&E) staining. The expressions of PTGS2 and NLRP3 inflammasome were also observed in the bladder tissues. A good binding activity was found between hispidulin and PTGS2 (score = - 8.9 kcal/mol). The levels of PTGS2 and NLRP3 inflammasome were decreased with the hispidulin dose increase in the IL-1ß-treated cells (p < 0.05). Cells overexpressing PTGS2 weakened the protective effects of hispidulin in the IL-1ß-treated cells (p < 0.01). In the CYP-treated rats, hispidulin treatment improved the bladder pain through decreasing the nociceptive score (p < 0.01) and suppressed the bladder inflammation through suppressing the expressions of PTGS2 and NLRP3 inflammasome in bladder tissues (p < 0.01). Additionally, the results of ibuprofen treatment were similar to the effects of hispidulin in the CYP-treated rats. This study demonstrates that hispidulin may be a new alternative drug for the IC treatment that binds PTGS2 to perform its functions.

Isolation and Purification of Protamine from the Cultured Takifugu flavidus and Its Physicochemical Properties.

Protamine is a cationic peptide derived from fish sperm and has several important functional properties: antibacterial properties, acting as a carrier for injectable insulin and as a heparin antagonist, combatting fatigue, etc. Thus, it has been widely used in medicinal applications and food products. Cultured Takifugu flavidus is a type of pufferfish with a delicious taste that is popular in China, and its production is increasing significantly. Therefore, protamine was extracted via acid extraction from the sperm of Takifugu flavidus and further isolated and purified via sephadex gel chromatography, ion exchange chromatography, and desalination chromatography. Furthermore, the physicochemical properties of protamine were investigated. The results showed that the sperm of the cultured T. flavidus were non-toxic, and the extracted and purified protamine had high contents of arginine (36.90%) and lysine (27.02%), respectively. The secondary structure of protamine was mainly ß-folded and irregularly curled. Additionally, protamine exhibited high thermal stability with a denaturation temperature of 176 °C. This study would provide a theoretical basis for the structural analysis, bioactivity, and resource development of pufferfish protamine and help to promote the development of the pufferfish industry.

Scapular dislocation following radical surgical excision of lung sarcomatoid carcinoma: A rare case report.

RATIONALE: Scapular prolapse is a rare complication of thoracotomy. Only a few cases of scapular prolapse after thoracotomy have been reported. Here, we report the case of a 52-year-old male patient who underwent standard posterior thoracotomy for lung sarcomatoid carcinoma invading the left upper chest wall. PATIENT CONCERNS: The surgery was performed to remove some ribs and chest wall muscles; however, no reconstruction or repair of the chest wall defect was performed. The patient experienced a sharp pain and severe limitation of movement of the left shoulder within 1 month of receiving adjuvant therapy. DIAGNOSES: The patient was diagnosed with left intrathoracic scapular prolapse after careful consideration of medical history, physical examination, and chest radiography. INTERVENTIONS: We performed closed manual reduction because the patient refused to undergo surgery. OUTCOMES: The patient's shoulder pain and movement limitation were significantly relieved, but the symptoms relapsed. After repeated closed manual reduction, the patient was instructed not to abduct the shoulder joint above 90°. The patient did not relapse during a 1-year observation period. CONCLUSION: If scapular prolapse occurs, manual or surgical reduction can be selected based on the needs. If a patient refuses to undergo surgery, manual reduction can be an effective treatment method.

Clinicopathological Characteristics of Breast Cancer Patients with HER-2 Low Expression Receiving Neoadjuvant Therapy.

INTRODUCTION: Human epidermal growth factor receptor-2 (HER-2) low expression breast malignant tumors have become a research hotspot in recent years, but it is still unclear whether HER-2 low expression represents a special subtype of breast cancer. However, this molecular type requires more effective treatment regimens in the neoadjuvant therapy stage. METHODS: This study enrolled breast cancer patients who were treated at Harbin Medical University Cancer Hospital with neoadjuvant treatment between October 2011 and May 2019 and was a single-center retrospective study. RESULTS: A total of 1,053 breast cancer patients who received preoperative therapy, including 279 (26%) HER-2 low expression patients, were included in this retrospective study. The HER-2 low expression group had a higher proportion of patients under 50 years old than the other two molecular subtype groups (p = 0.047, 62.0% vs. 57.2% and 52.5%), and the percentage of patients with Ki67 index above 15% was lower than that in HER-2-negative and HER-2-positive patients (p < 0.001, 50.2% vs. 63.6% and 71.5%). Most of the patients with HER-2 low expression were hormone receptor (HR) positive (p < 0.001, 85.7% vs. 60.4% and 36.0%), and their pathologic complete response (pCR) rate after neoadjuvant therapy was significantly lower than that of HER-2-negative and HER-2-positive patients (p < 0.001, 5.7% vs. 11.8% and 20.5%). The results of the subgroup analysis showed HR-positive patients with HER-2 low expression had a lower pCR rate (p < 0.001, 4.6% vs. 14.6%) and objective response rate (p = 0.001, 77.8% vs. 91.0%) than HER-2-positive patients and had no significant difference in these rates compared to HER-2-negative patients. There were no significant differences in overall survival (OS) and disease-free survival (DFS) up to 67 months (the median follow-up time) among HER-2 low, HER-2-negative, and HER-2-positive patients. The results of Cox hazard proportional showed that the Ki67 index and T stage (T3) were independent influencing factors for DFS. In terms of OS, Ki67 index, P53, T stage, and objective response were independent influencing factors for OS in HER-2 low expression patients. CONCLUSIONS: In general, further studies are needed to confirm that HER-2 low expression is a special breast cancer molecular subtype. The efficacy of neoadjuvant therapy in patients with HER-2 low expression is relatively poor, and the efficacy of neoadjuvant therapy can predict the prognosis of patients with HER-2 low expression.

Chlorella pyrenoidosa as a potential bioremediator: Its tolerance and molecular responses to cadmium and lead.

Heavy metal contamination negatively affects plants and animals in water as well as soils. Some microalgae can remove heavy metal contaminants from wastewater. The aim of this study was to screen green microalgae (GM) to identify those that tolerate high concentrations of toxic heavy metals in water as possible candidates for phytoremediation. Analyses of the tolerance, physiological parameters, ultrastructure, and transcriptomes of GM under Cd/Pb treatments were conducted. Compared with the other GM, Chlorella pyrenoidosa showed stronger tolerance to high concentrations of Cd/Pb. The reduced glutathione content and peroxidase activity were higher in C. pyrenoidosa than those in the other GM. Ultrastructural observations showed that, compared with other GM, C. pyrenoidosa had less damage to the cell surface and interior under Cd/Pb toxicity. Transcriptome analyses indicated that the "peroxisome" and "sulfur metabolism" pathways were enriched with differentially expressed genes under Cd/Pb treatments, and that CpSAT, CpSBP, CpKAT2, Cp2HPCL, CpACOX, CpACOX2, and CpACOX4, all of which encode antioxidant enzymes, were up-regulated under Cd/Pb treatments. These results show that C. pyrenoidosa has potential applications in the remediation of polluted water, and indicate that antioxidant enzymes contribute to Cd/Pb detoxification. These findings will be useful for producing algal strains for the purpose of bioremediation in water contamination.