Biodegradation of various grades of polyethylene microplastics by Tenebrio molitor and Tenebrio obscurus larvae: Effects on their physiology.

Polyethylene (PE) is the most productive plastic product and includes three major polymers including high-density polyethylene (HDPE), linear low-density polyethylene (LLDPE) and low-density polyethylene (LDPE) variation in the PE depends on the branching of the polymer chain and its crystallinity. Tenebrio obscurus and Tenebrio molitor larvae biodegrade PE. We subsequently tested larval physiology, gut microbiome, oxidative stress, and PE degradation capability and degradation products under high-purity HDPE, LLDPE, and LDPE powders (<300 µm) diets for 21 days at 65 ± 5% humidity and 25 ± 0.5 °C. Our results demonstrated the specific PE consumption rates by T. molitor was 8.04-8.73 mg PE ∙ 100 larvae-1⋅day-1 and by T. obscurus was 7.68-9.31 for LDPE, LLDPE and HDPE, respectively. The larvae digested nearly 40% of the ingested three PE and showed similar survival rates and weight changes but their fat content decreased by 30-50% over 21-day period. All the PE-fed groups exhibited adverse effects, such as increased benzoquinone concentrations, intestinal tissue damage and elevated oxidative stress indicators, compared with bran-fed control. In the current study, the digestive tract or gut microbiome exhibited a high level of adaptability to PE exposure, altering the width of the gut microbial ecological niche and community diversity, revealing notable correlations between Tenebrio species and the physical and chemical properties (PCPs) of PE-MPs, with the gut microbiome and molecular weight change due to biodegradation. An ecotoxicological simulation by T.E.S.T. confirmed that PE degradation products were little ecotoxic to Daphnia magna and Rattus norvegicus providing important novel insights for future investigations into the environmentally-friendly approach of insect-mediated biodegradation of persistent plastics.

Nuclear phylogenomics of Asteraceae with increased sampling provides new insights into convergent morphological and molecular evolution.

Convergent morphological evolution is widespread in flowering plants, and understanding this phenomenon relies on well-resolved phylogenies. Nuclear phylogenetic reconstruction using transcriptome datasets has been successful in various angiosperm groups, but it is limited to taxa with available fresh materials. Asteraceae, which are one of the two largest angiosperm families and are important for both ecosystems and human livelihood, show multiple examples of convergent evolution. Nuclear Asteraceae phylogenies have resolved relationships among most subfamilies and many tribes, but many phylogenetic and evolutionary questions regarding subtribes and genera remain, owing to limited sampling. Here, we increased the sampling for Asteraceae phylogenetic reconstruction using transcriptomes and genome-skimming datasets and produced nuclear phylogenetic trees with 706 species representing two-thirds of recognized subtribes. Ancestral character reconstruction supports multiple convergent evolutionary events in Asteraceae, with gains and losses of bilateral floral symmetry correlated with diversification of some subfamilies and smaller groups, respectively. Presence of the calyx-related pappus may have been especially important for the success of some subtribes and genera. Molecular evolutionary analyses support the likely contribution of duplications of MADS-box and TCP floral regulatory genes to innovations in floral morphology, including capitulum inflorescences and bilaterally symmetric flowers, potentially promoting the diversification of Asteraceae. Subsequent divergences and reductions in CYC2 gene expression are related to the gain and loss of zygomorphic flowers. This phylogenomic work with greater taxon sampling through inclusion of genome-skimming datasets reveals the feasibility of expanded evolutionary analyses using DNA samples for understanding convergent evolution.

Antigen-specific T cell activation through targeted delivery of in-situ generated antigen and calcium ionophore to enhance antitumor immunotherapy.

Recent advances in adoptive T-cell therapy have delivered impressive therapeutic outcomes by instigating enduring anti-tumor responses. Nonetheless, achieving specific T-cell activation remains a challenge due to several factors. Some cancer cells evade T-cell recognition due to the scarcity of tumor-specific T cells and deficiencies in antigen processing or major histocompatibility complex (MHC) presentation. Notably underestimated is the impact of waning T-cell receptor (TCR) expression and the constrained formation of immune synapses (IS) between dendritic cells (DCs) and T cells, impairing T-cell activation. Addressing these complexities, we introduce a pioneering approach featuring the deployment of a gel implant. This implant establishes an on-site antigen reservoir, efficiently targets DCs in lymph nodes, and facilitates calcium ion (Ca2+) delivery. Engineered with controlled swelling, poroelasticity, and resilience, the gel is suitable for surgical implantation. Its ample encapsulation capacity accommodates both photosensitizers and nanoparticles. Upon in situ photothermal irradiation, the gel generates tumor-specific antigens. Furthermore, cationic albumin nanoparticles (cNPs) co-loaded with monophosphoryl lipid A (MPLA) and ionomycin are released, guiding antigens to tumor-draining lymph nodes for DCs maturation. This meticulous process fosters the formation of IS thereby amplifying antigen-specific T-cell activation.

Hemoglobin levels and clinical outcomes after extracorporeal circulation auxiliary to open heart surgery: a retrospective cohort study.

BACKGROUND: Extracorporeal circulation auxiliary to open heart surgery is a common procedure used to treat heart diseases. However, the optimal transfusion strategy for patients undergoing this surgery remains a subject of debate. This study aims to investigate the association between hemoglobin levels and clinical outcomes in patients undergoing extracorporeal circulation auxiliary to open heart surgery, with the ultimate goal of improving surgical success rates and enhancing patients' quality of life. METHODS: A retrospective analysis was conducted on data from the Medical Information Mart for Intensive Care IV 2.2 (MIMIC-IV 2.2) database, including 4144 patients. The patients were categorized into five groups based on their minimum hemoglobin levels during hospitalization. Baseline characteristics, clinical scores, laboratory results, and clinical outcome data were collected. Statistical analyses utilized descriptive statistics, ANOVA or Kruskal-Wallis tests, Kaplan-Meier method, and Log-rank test. RESULTS: The results revealed a significant correlation between hemoglobin levels and in-hospital mortality, as well as mortality rates at 30 days, 60 days, and 180 days (p < 0.001). Patients with lower hemoglobin levels exhibited higher mortality rates. However, once hemoglobin levels exceeded 7g/dL, no significant difference in mortality rates was observed (p = 0.557). Additionally, lower hemoglobin levels were associated with prolonged hospital stay, ICU admission time, and mechanical ventilation time (p < 0.001). Furthermore, hemoglobin levels were significantly correlated with complication risk, norepinephrine dosage, and red blood cell transfusion volume (p < 0.001). However, there was no significant difference among the groups in terms of major complications, specifically sepsis (p > 0.05). CONCLUSION: The study highlights the importance of managing hemoglobin levels in patients undergoing heart surgery with extracorporeal circulation. Hemoglobin levels can serve as valuable indicators for predicting clinical outcomes and guiding treatment decisions. Physicians should carefully consider hemoglobin levels to optimize transfusion strategies and improve postoperative patient outcomes. Further research and intervention studies are warranted to validate and implement these findings in clinical practice.

[Clinical Features and Prognostic Factors of Patients with Primary Cutaneous Lymphoma].

OBJECTIVE: To retrospectively analyze the clinical characteristics and prognostic factors of patients with primary cutaneous lymphoma. METHODS: The clinical data of 22 patients with primary cutaneous lymphoma admitted to Xinjiang Hotan District People's Hospital, Heji Hospital affiliated to Changzhi Medical College and the Fifth Medical Center of PLA General Hospital from January 2013 to June 2021 were retrospectively analyzed. RESULTS: The incidence of primary cutaneous T cell and NK/T cell lymphoma was about 91.9/100 000, and the incidence of primary cutaneous B cell lymphoma was about 14.5/100 000. The overall survival (OS) of patients aged ≥65 years was significantly shorter than that of patients younger than 65 years (P <0.05). Patients with elevated ß2-microglobulin (ß2-MG) had shorter OS and progression-free survival (PFS) (both P <0.05). Patients who achieved complete/partial response after initial treatment had longer OS than those with stable or progressive disease (P <0.05). There were significant differences in OS and PFS among patients with different pathological types of primary cutaneous lymphoma that originated from T and NK/T cells, the OS and PFS of patients with mycosis fungoides were longer than those of patients with other pathological types (both P <0.05). In addition, disease stage might also affect the PFS of the patients (P =0.056). CONCLUSION: The age, disease stage, ß2-MG level, pathological type and remission state after treatment of the patients were related to the clinical prognosis.

A retrospective study of Kaposi's sarcoma in Hotan region of Xinjiang, China.

Kaposi sarcoma (KS) is the most common cancer in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (AIDS). In 1994, Chang and Moore discovered Kaposi sarcoma associated herpesvirus for the first time in KS lesions in AIDS patients. KS is a low-grade mesenchymal neoplasm of blood and lymphatic vessels that primarily affects the skin, although the disease may become disseminated to the lymphatic system, lungs, airways, or abdominal viscera. In this research, clinical characteristics and treatment of patients of Kaposi sarcoma were retrospectively analyzed in Hotan District, Xinjiang China. We look into the clinical traits, prognosis, and therapy of Kaposi sarcoma. From May 2017 to August 2022, 32 patients were treated in the People's Hospital of Hotan District, Xinjiang Uygur Autonomous Region, China. Twenty-two of these were classic Kaposi sarcomas (cKS), and 10 of these were Kaposi sarcomas linked to AIDS (AIDS-KS). The majority of KS patients were Uyghur. In terms of age at onset, AIDS-KS patients were younger than cKS patients. cKS and AIDS-KS are most frequently manifested in the feet and lower limbs. Ten patients with AIDS-KS have treated with combination antiretroviral therapy (combination antiretroviral therapy) combination chemotherapy, 5 of 10 patients had a complete response, 2 patients achieved partial response, the overall effective rate was 70%, and CD4 + T cells were greater than before. For cKS and AIDS-KS, the median overall survival was 56 and 50.8 months, respectively (P > .05). As a result, antiviral combination chemotherapy can also improve the prognosis of AIDS-KS patients.

Hemophagocytic lymphohistiocytosis after autologous stem cell transplantation in angioimmunoblastic T-cell lymphoma: A case report.

BACKGROUND: Angioimmunoblastic T-cell lymphoma (AITL), a unique subtype of peripheral T-cell lymphoma, has relatively poor outcomes. High-dose chemotherapy with autologous stem cell transplantation (ASCT) can achieve complete remission and improve outcomes. Unfortunately, subsequent T-cell lymphoma-triggered hemophagocytic lymphohistiocytosis (HLH) has a worse prognosis than B-cell lymphoma-triggered HLH. CASE SUMMARY: We here report a 50-year-old woman with AITL who achieved a favorable outcome after developing HLH 2 mo after receiving high-dose chemotherapy/ ASCT. The patient was initially admitted to our hospital because of multiple enlarged lymph nodes. The final pathologic diagnosis, made on biopsy of a left axillary lymph node was AITL (Stage IV, Group A). Four cycles of the following chemotherapy regimen were administered: Cyclophosphamide 1.3 g, doxorubicin 86 mg, and vincristine 2 mg on day 1; prednisone 100 mg on days 1-5; and lenalidomide 25 mg on days 1-14. The interval between each cycle was 21 d. The patient received a conditioning regimen (busulfan, cyclophosphamide, and etoposide) followed by peripheral blood stem cell infusion. Unfortunately, she developed sustained fever and a low platelet count 17 d after ACST, leading to a diagnosis of HLH after ASCT. During treatment, she experienced thrombocytopenia and Pneumocystis carinii pneumonia. The patient was successfully treated with etoposide and glucocorticoids. CONCLUSION: It is possible that development of HLH is related to immune reconstitution after ASCT.

Gut Microbiome Associating with Carbon and Nitrogen Metabolism during Biodegradation of Polyethene in Tenebrio larvae with Crop Residues as Co-Diets.

Tenebrio molitor and Tenebrio obscurus (Coleoptera: Tenebrionidae) larvae are two commercial insects that eat plant and crop residues as diets and also biodegrade synthetic plastics polyethylene (PE). We examined biodegradation of low-density PE (LDPE) foam (Mn = 28.9 kDa and Mw = 342.0 kDa) with and without respective co-diets, i.e., wheat brain (WB) or corn flour (CF), corn straw (CS), and rice straw (RS) at 4:1 (w/w), and their gut microbiome and genetic metabolic functional groups at 27.0 ± 0.5 °C after 28 days of incubation. The presence of co-diets enhanced LDPE consumption in both larvae and broad-depolymerized the ingested LDPE. The diet type shaped gut microbial diversity, potential pathways, and metabolic functions. The sequence of effectiveness of co-diets was WB or CF > CS > RS for larval development and LDPE degradation. Co-occurrence networks indicated that the larvae co-fed with LDPE displayed more complex correlations of gut microbiome than the larvae fed with single diets. The primary diet of WB or CF and crop residues CS and RS provided energy and nitrogen source to significantly enhance LDPE biodegradation with synergistic activities of the gut microbiota. For the larvae fed LDPE and LDPE plus co-diets, nitrogen fixation function was stimulated compared to normal diets and associated with LDPE biodegradation.

DNA barcoding of Cymbidium by genome skimming: Call for next-generation nuclear barcodes.

Cymbidium is an orchid genus that has undergone rapid radiation and has high ornamental, economic, ecological and cultural importance, but its classification based on morphology is controversial. The plastid genome (plastome), as an extension of plant standard DNA barcodes, has been widely used as a potential molecular marker for identifying recently diverged species or complicated plant groups. In this study, we newly generated 237 plastomes of 50 species (at least two individuals per species) by genome skimming, covering 71.4% of members of the genus Cymbidium. Sequence-based analyses (barcoding gaps and automatic barcode gap discovery) and tree-based analyses (maximum likelihood, Bayesian inference and multirate Poisson tree processes model) were conducted for species identification of Cymbidium. Our work provides a comprehensive DNA barcode reference library for Cymbidium species identification. The results show that compared with standard DNA barcodes (rbcL + matK) as well as the plastid trnH-psbA, the species identification rate of the plastome increased moderately from 58% to 68%. At the same time, we propose an optimized identification strategy for Cymbidium species. The plastome cannot completely resolve the species identification of Cymbidium, the main reasons being incomplete lineage sorting, artificial cultivation, natural hybridization and chloroplast capture. To further explore the potential use of nuclear data in identifying species, the Skmer method was adopted and the identification rate increased to 72%. It appears that nuclear genome data have a vital role in species identification and are expected to be used as next-generation nuclear barcodes.

Comparison of two methods for tumour-targeting peptide modification of liposomes.

Liposomes decorated with tumour-targeting cell-penetrating peptides can enhance specific drug delivery at the tumour site. The TR peptide, c(RGDfK)-AGYLLGHINLHHLAHL(Aib)HHIL, is pH-sensitive and actively targets tumour cells that overexpress integrin receptor αvß3, such as B16F10 melanoma cells. Liposomes can be modified with the TR peptide by two different methods: utilization of the cysteine residue on TR to link DSPE-PEG2000-Mal contained in the liposome formula (LIPTR) or decoration of TR with a C18 stearyl chain (C18-TR) for direct insertion into the liposomal phospholipid bilayer through electrostatic and hydrophobic interactions (LIPC18-TR). We found that both TR and C18-TR effectively reversed the surface charge of the liposomes when the systems encountered the low pH of the tumour microenvironment, but LIPC18-TR exhibited a greater increase in the charge, which led to higher cellular uptake efficiency. Correspondingly, the IC50 values of PTX-LIPTR and PTX-LIPC18-TR in B16F10 cells in vitro were 2.1-fold and 2.5-fold lower than that of the unmodified PTX-loaded liposomes (PTX-LIP), respectively, in an acidic microenvironment (pH 6.3). In B16F10 tumour-bearing mice, intravenous administration of PTX-LIPTR and PTX-LIPC18-TR (8 mg/kg PTX every other day for a total of 4 injections) caused tumour reduction ratios of 39.4% and 56.1%, respectively, compared to 20.8% after PTX-LIP administration. Thus, we demonstrated that TR peptide modification could improve the antitumour efficiency of liposomal delivery systems, with C18-TR presenting significantly better results. After investigating different modification methods, our data show that selecting an adequate method is vital even when the same molecule is used for decoration.

Efficacy and safety of esophagectomy via left thoracic approach versus via right thoracic approach for middle and lower thoracic esophageal cancer: a multicenter randomized clinical trial (NST1501).

Background: Left thoracic approach (LTA) has been a favorable selection in surgical treatment for esophageal cancer (EC) patients in China before minimally invasive esophagectomy (MIE) is popular. This study aimed to demonstrate whether right thoracic approach (RTA) is superior to LTA in the surgical treatment of middle and lower thoracic esophageal squamous cell carcinoma (TESCC). Methods: Superiority clinical trial design was used for this multicenter randomized controlled two-parallel group study. Between April 2015 and December 2018, cT1b-3N0-1M0 TESCC patients from 14 centers were recruited and randomized by a central stratified block randomization program into LTA or RTA groups. All enrolled patients were followed up every three months after surgery. The software SPSS 20.0 and R 3.6.2. were used for statistical analysis. Efficacy and safety outcomes, 3-year overall survival (OS) and disease-free survival (DFS) were calculated and compared using the Kaplan-Meier method and the log-rank test. Results: A total of 861 patients without suspected upper mediastinal lymph nodes (umLN) were finally enrolled in the study after 95 ineligible patients were excluded. 833 cases (98.7%) were successfully followed up until June 1, 2020. Esophagectomies were performed via LTA in 453 cases, and via RTA in 408 cases. Compared with the LTA group, the RTA group required longer operating time (274.48±78.92 vs. 205.34±51.47 min, P<0.001); had more complications (33.8% vs. 26.3% P=0.016); harvested more lymph nodes (LNs) (23.61±10.09 vs. 21.92±10.26, P=0.015); achieved a significantly improved OS in stage IIIa patients (67.8% vs. 51.8%, P=0.022). The 3-year OS and DFS were 68.7% and 64.3% in LTA arm versus 71.3% and 63.7% in RTA arm (P=0.20; P=0.96). Conclusions: Esophagectomies via both LTA and RTA can achieve similar outcomes in middle or lower TESCC patients without suspected umLN. RTA is superior to LTA and recommended for the surgical treatment of more advanced stage TESCC due to more complete lymphadenectomy. Trial Registration: ClinicalTrials.gov NCT02448979.

Targeted delivery via albumin corona nanocomplex to renal tubules to alleviate acute kidney injury.

Renal tubular epithelial cell (RTEC) is a critical target cell for the treatment of acute kidney injury (AKI). Despite various RTEC targeting strategies using ligand modified nanoparticles (NPs) following systemic administration, the nonspecific interaction between NPs and plasma proteins greatly weakens the targeting efficiency as well as the stability of NPs. Herein, celastrol (CLT) was entrapped in D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) forming a CLT-loaded nanocomplex core (CT) with a high loading capacity of ~50%. Bovine serum albumin (BSA) was then adsorbed onto the CT surface to afford a complete albumin corona without obvious denaturation (CTB). CTB showed uniform particle size distribution and sufficient stability in vitro and in vivo. Besides clathrin-mediated and macropinocytosis pathways, CTB was actively internalized through megalin receptor-mediated endocytosis in HK-2 cells. Per biodistribution studies, CTB demonstrates enhanced renal tubule-specific distribution and targetability in mice compared to CT without albumin corona. Furthermore, pharmacodynamic studies in vivo further support that CTB effectively alleviated ischemia-reperfusion induced injuries without obvious systemic side effects in AKI mice models.

Characterization of the complete plastid genome of Scutellaria microviolacea (Lamiaceae), a species endemic to Yunnan Province of China.

The complete plastid genome of Scutellaria microviolacea C. Y. Wu was firstly reported. The full length of the plastid genome was 152,092 bp and comprised of a large single-copy (LSC) region of 84,090 bp, a small single-copy (SSC) region of 17,534 bp, and two inverted repeat regions (IRs) of 25,234 bp. A total of 131 genes were encoded, including 87 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. The overall GC content of the S. microviolacea plastid genome was 38.3%. Further phylogenetic analysis based on 18 accessions inferred that the genus Scutellaria can be divided into two clades, and S. microviolacea is evolutionarily close to Scutellaria tsinyunensis. Our study provided essential genetic resources for further studies on the evolution and genetic diversity of the genus Scutellaria and its related taxa.

Chondroitin sulfate-based prodrug nanoparticles enhance photodynamic immunotherapy via Golgi apparatus targeting.

Photodynamic therapy (PDT) is an emerging therapeutic approach that can inhibit tumor growth by destroying local tumors and activating systemic antitumor immune responses. However, PDT can be ineffective because of photosensitizer aggregation, tumor-induced dendritic cells (DCS) dysfunction and PDT-mediated immunosuppression. Therefore, we designed chondroitin sulfate-based prodrug nanoparticles for the co-delivery of the photosensitizer chlorin e6 (Ce6) and retinoic acid (RA), which can reduce PDT-mediated immunosuppression by disrupting the Golgi apparatus and blocking the production of immunosuppressive cytokines. Moreover, CpG oligodeoxynucleotide was combined as immunoadjuvant to promote the maturation of DCs. As expected, the strategy of Golgi apparatus targeting immunotherapy combined PDT was confirmed to relieve PDT-induced immunosuppression, showed excellent PDT antitumor efficacy in B16F10-subcutaneous bearing mice model. Thus, our finding offers a promising approach for photodynamic immunotherapy of advanced cancers. STATEMENT OF SIGNIFICANCE: Golgi apparatus has been shown to be a potential target of immunosuppression for producing several immunosuppressive cytokines. In this work, a Golgi apparatus-targeted prodrug nanoparticle was developed to enhance the immune response in photodynamic immunotherapy. The nanoparticle can target and disrupt the Golgi apparatus in tumor cells, which reduced PDT-mediated immunosuppression by blocking the production of immunosuppressive cytokines. This work provides an effective strategy of PDT in combination with the Golgi apparatus-targeted nanovesicle for enhanced cancer therapy.

Testing the Complete Plastome for Species Discrimination, Cryptic Species Discovery and Phylogenetic Resolution in Cephalotaxus (Cephalotaxaceae).

Species of Cephalotaxus have great economic and ecological values. However, the taxonomy and interspecific phylogenetic relationships within the genus have been controversial and remained not fully resolved until now. To date, no study examined the efficiency of the complete plastome as super-barcode across Cephalotaxus species with multiple samples per taxon. In this study, we have evaluated the complete plastome in species discrimination and phylogenetic resolution in Cephalotaxus by including 32 individuals of all eight recognized species and five varieties following Farjon's classification (2010) with multiple samples per taxon. Our results indicated that not all species recognized in recent taxonomic revisions of Cephalotaxus could be distinguished and not all were monophyletic. Based on the plastome phylogeny, a new taxonomic classification for the genus comprising nine species and two varieties, including a cryptic species, was proposed. The phylogeny also resolved all interspecific relationships. Compared to the plastome based classification, standard DNA barcodes, alone or in combination, only recognized a maximum of seven out of the nine species. Moreover, two highly variable single loci, ycf1 and rps16, each alone achieved full species discrimination. With the moderate length of 1079 bp, rps16 is proposed as a specific barcode to discriminate Cephalotaxus species. The super-barcodes and specific barcode candidates will aid in the identification of endangered Cephalotaxus species, and to help focus conservation measures.

[Effect of Acute Myeloid Leukemia Cells on the Proliferation and Apoptosis of Bone Marrow-Derived Mesenchymal Stromal Cells].

OBJECTIVE: To investigate the effect of acute myeloid leukemia cells in leukemia-microenvironment on proliferation and apoptosis of bone marrow-derived mesenchymal stromal cells (BM-MSC). METHODS: Acute myeloid leukemia (AML) murine models overexpressing MLL-AF9 were established. The number of BM-MSC of wild type (WT) and AML-derived mice were analyzed by flow cytometry. Morphology and growth differences between WT and AML-derived BM-MSC were analyzed by inverted fluorescence microscope. Proliferation and apoptosis of BM-MSC between these two groups were detected by Brdu and Annexin V/PI. RESULTS: Compared with WT-derived BM-MSC, the number and proliferation rate of AML-derived BM-MSC significantly increased (P<0.01, P<0.001), while apoptosis rate decreased (P<0.05). When cultured in vitro, BM-MSC grew faster under conditional medium. CONCLUSION: AML cells can promote proliferation and inhibit apoptosis of BM-MSC.

Impacts of physical-chemical property of polyethylene on depolymerization and biodegradation in yellow and dark mealworms with high purity microplastics.

Yellow and dark mealworms (Tenebrio molitor and Tenebrio obscurus) biodegrade commercial polyethylene (PE) materials at a high rate. We examined the impact of physical and chemical properties on biodegradation using high purity microplastics (MPs). These included high-density polyethylene (HDPE), low-density polyethylene (LDPE), and linear low-density polyethylene (LLDPE), all with different weight average molecular weights (Mw) and different crystallinity degrees in T. molitor and T. obscurus larvae. The biodegradation extent in the two mealworms was similar but strongly depended on the polymer type in sequence, since LDPE > LLDPE> HDPE (with respective Mw of 222.5, 110.5 and 182 kDa). When LDPE MPs with Mw of 0.84, 6.4 and 106.8 kDa and HDPE with Mw of 52, 105 and 132.7 kDa were tested, the PE MPs with lower Mw showed a greater extent of depolymerization. The results of dominance analysis indicated that less branching structure and higher crystallinity degree negatively impacted depolymerization and biodegradation. Py-GC/MS analysis confirmed the breaking of the macromolecule backbone as well as the formation of oxidized functional groups after all the tested PE materials passed through the mealworm intestine. The results demonstrated that molecular weight, PE type, branching, and crystallinity degree significantly affect the biodegradation capability of PE by the mealworms, and possibly by other biological systems as well.

[Reflections on and Preliminary Practice of Pharmaceutical Curriculum Structure Reform under the Guidance of Coordinated Development Concept].

The structure of pharmaceutical higher education in China needs to be adjusted under the guidance of Xi Jinping's new development philosophy, especially the concept of coordinated development, in order to meet the demands of the campaign to construct new medical education and to develop in coordination with the pharmaceutical industry. Based on the concept of coordinated development, we summarized herein the relationship between pharmaceutical higher education, pharmaceutical research and the pharmaceutical industry, analyzed the adaptability of pharmaceutical higher education and the pharmaceutical industry, and put forward suggestions for and implemented initially the reform of the pharmaceutical curriculum structure under the guidance of the concept of coordinated development. We hope this paper will, under the new circumstances, provide useful reference for the ongoing education reform of the curricular structure of pharmaceutical higher education and pharmaceutical research coordinated along with the development of the pharmaceutical industry.

In situ gel implant for postsurgical wound management and extended chemoimmunotherapy against breast cancer recurrence.

Postsurgical recurrence of breast cancer is closely related to the inflammatory tumor microenvironment evoked by surgical wounds. Toll-like receptor 4 (TLR4) signaling contributes to NF-κB activation thus secreting various inflammatory cytokines. Herein, we developed an in situ photo-crosslinked hydrogel (D/T gel) concurrently loaded with doxorubicin (DOX) and a TLR4 antagonist, resatorvid (TAK-242). Its therapeutic effect against breast cancer postsurgical relapse was accomplished through remodeling the proinflammatory tumor microenvironment. The obtained gel network exhibited ideal biodegradability and biocompatibility, which motivated dermal wound healing in the full thickness wound model in mice. Despite the initial burst release of DOX, D/T gels exhibited extended-release of both DOX and TAK-242 for up to 21 days in vitro. TAK-242 was demonstrated to inhibit the lipopolysaccharide-induced NF-κB activation and downregulate TLR4 levels in both RAW264.7 and 4T1 cells. In a 4T1-Luc tumor postsurgical recurrence model, D/T gel significantly suppressed recurrent tumor growth by elevating the concentrations of DOX and TAK-242 at the tumor sites and remodeling the TLR4 activation-induced proinflammatory microenvironment. Overall, the D/T gel platform technology is proven to deliver therapeutics directly to the surgical wound bed, attenuating the dual inflammatory responses induced by DOX and surgical wounding thus greatly potentiating its efficacy in preventing postsurgical tumor recurrence. STATEMENT OF SIGNIFICANCE: Postsurgical recurrence of breast cancer is closely related to the inflammatory tumor microenvironment (TME) evoked by surgical wounds. Although chemotherapeutics lead to extensive residual tumor cell necrosis, multiple inflammatory cytokines are secreted simultaneously, which are conducive to tumor recurrence. In this work, a TLR4 antagonist, TAK-242, was combined with DOX to reverse the dual inflammatory TME induced by surgical wounding and chemotherapy. To elevate the concentration of therapeutics at the tumor site, a photocrosslinked hydrogel (D/T gel) implant coloaded with TAK-242 and DOX was developed and applied on the postsurgical bed. Consequently, D/T gel attenuated the dual inflammatory responses and greatly potentiated its efficacy in preventing postsurgical tumor recurrence.