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Lordithon species are typically mushroom-dwelling rove beetles that devour maggots. This study presents the mitogenome of a Lordithon arcuatus specimen that was procured from Changbai Mountain in the Jilin Province of China. The mitogenome is 18,290 bp long and comprises 13 protein-coding genes, 22 tRNAs, and 2 rRNAs. The base composition of the mitogenome is as follows: A = 38.80%, T = 37.93%, G = 8.94%, and C = 14.32%. Maximum likelihood and Bayesian phylogenetic trees were constructed using 68 representative staphylinid species, which showed that Lordithon, Bolitobius, and Ischnosoma form a stable and fully supported Mycetoporinae clade, whereas there was no consensus regarding the relationships among Tachyporinae taxa. Additionally, the performance of site-specific mixture models for inferring the phylogeny of staphylinids using mitogenomic data was assessed. The results suggest that heterotachy models should be used with caution, as they may result in incorrect topology with delusive precedence in AIC- or BIC-based model selection.

Abstract The energy dissipation pathways of a photosensitizer for phototherapies, including photodynamic therapy (PDT) and photothermal therapy (PTT), compete directly with that of its fluorescence (FL) emission. Enriching heavy atoms on the π‐conjugated systems and aggregation‐caused quenching are two effective methods to turn off the FL emission of photosensitizers, which is expected to boost the intersystem crossing (for PDT) and nonradiative transition (for PTT) of photosensitizers for maximized phototherapeutic efficacy. Following this approach, an all‐iodine‐substituted polydiacetylene aggregate poly(diiododiacetylene) (PIDA) has been developed, which shows a superior near infrared absorption (ε808nm = 26.1 g−1 cm−1 L) with completely blocked FL, as well as high efficiency of reactive oxygen species generation (nearly 45 folds of indocyanine green) and photothermal conversion (33.4%). To make the insoluble fibrillar PIDA aggregates favorable for systemic administration, they are converted into nanospheres through a pre‐polymerization morphology transformation strategy. The in vivo study on a 4T1 tumor‐bearing mouse model demonstrates that PIDA nanospheres can almost eliminate the tumor entirely in 16 days and prolong the survival time of mice to over 60 days, validating their effective phototherapeutic response through the strategy of inhibiting FL for boosted intersystem crossing and nonradiative transition.

Abstract FAAP20 is a Fanconi anemia (FA) protein that associates with the FA core complex to promote FANCD2/FANCI monoubiquitination and activate the damage response to interstrand crosslink damage. Here, we report that FAAP20 has a marked role in homologous recombination at a DNA double-strand break not associated with an ICL and separable from its binding partner FANCA. While FAAP20’s role in homologous recombination is not dependent on FANCA, we found that FAAP20 stimulates FANCA’s biochemical activity in vitro and participates in the single-strand annealing pathway of double-strand break repair in a FANCA-dependent manner. This indicates that FAAP20 has roles in several homology-directed repair pathways. Like other homology-directed repair factors, FAAP20 loss causes a reduction in nuclear RAD51 Irradiation-induced foci; and sensitizes cancer cells to ionizing radiation and PARP inhibition. In summary, FAAP20 participates in DNA double strand break repair by supporting homologous recombination in a non-redundant manner to FANCA, and single-strand annealing repair via FANCA-mediated strand annealing activity.

Chronic diabetic wounds remain a globally recognized clinical challenge. They occur due to high concentrations of reactive oxygen species and vascular function disorders. A promising strategy for diabetic wound healing is the delivery of exosomes, comprising bioactive dressings. Metformin activates the vascular endothelial growth factor pathway, thereby improving angiogenesis in hyperglycemic states. However, multifunctional hydrogels loaded with drugs and bioactive substances synergistically promote wound repair has been rarely reported, and the mechanism of their combinatorial effect of exosome and metformin in wound healing remains unclear. Here, we engineered dual-loaded hydrogels possessing tissue adhesive, antioxidant, self-healing and electrical conductivity properties, wherein 4-armed SH-PEG cross-links with Ag+, which minimizes damage to the loaded goods and investigated their mechanism of promotion effect for wound repair. Multiwalled carbon nanotubes exhibiting good conductivity were also incorporated into the hydrogels to generate hydrogen bonds with the thiol group, creating a stable three-dimensional structure for exosome and metformin loading. The diabetic wound model of the present study suggests that the PEG/Ag/CNT-M + E hydrogel promotes wound healing by triggering cell proliferation and angiogenesis and relieving peritraumatic inflammation and vascular injury. The mechanism of the dual-loaded hydrogel involves reducing the level of reactive oxygen species by interfering with mitochondrial fission, thereby protecting F-actin homeostasis and alleviating microvascular dysfunction. Hence, we propose a drug–bioactive substance combination therapy and provide a potential mechanism for developing vascular function-associated strategies for treating chronic diabetic wounds.

Artificial cells have received much attention in recent years as cell mimics with typical biological functions that can be adapted for therapeutic and diagnostic applications, as well as having an unlimited supply. Although remarkable progress has been made to construct complex multifunctional artificial cells, there are still significant differences between artificial cells and natural cells. It is therefore important to understand the techniques and challenges for the fabrication of artificial cells and their applications for further technological advancement. The key concepts of top-down and bottom-up methods for preparing artificial cells are summarized, and the advantages and disadvantages of the bottom-up methods are compared and critically discussed in this review. Potential applications of artificial cells as drug carriers (microcapsules), as signaling regulators for coordinating cellular communication and as bioreactors for biomolecule fabrication, are further discussed. The challenges and future trends for the development of artificial cells simulating the real activities of natural cells are finally described.

The United Nations Secretary-General Mechanism (UNSGM) for investigation of the alleged use of chemical and biological weapons is the only established international mechanism of this type under the UN. The UNGSM may launch an international investigation, relying on a roster of expert consultants, qualified experts, and analytical laboratories nominated by the member states. Under the framework of the UNSGM, we organized an external quality assurance exercise for nominated laboratories, named the Disease X Test, to improve the ability to discover and identify new pathogens that may cause possible epidemics and to determine their animal origin. The “what-if” scenario was to identify the etiological agent responsible for an outbreak that has tested negative for many known pathogens, including viruses and bacteria. Three microbes were added to the samples, Dabie bandavirus, Mammarenavirus, and Gemella spp., of which the last two have not been taxonomically named or published. The animal samples were from Rattus norvegicus, Marmota himalayana, New Zealand white rabbit, and the tick Haemaphysalis longicornis. Of the 11 international laboratories that participated in this activity, six accurately identified pathogen X as a new Mammarenavirus, and five correctly identified the animal origin as R. norvegicus. These results showed that many laboratories under the UNSGM have the capacity and ability to identify a new virus during a possible international investigation of a suspected biological event. The technical details are discussed in this report.

Background: Sepsis is a fatal disease with a high rate of morbidity and mortality, during which acute lung injury is the earliest and most serious complication. Injury of pulmonary microvascular endothelial cells (PMVECs) induced by excessive inflammation plays an important role in sepsis acute lung injury. This study is meant to explore the protective effect and mechanism of ADSCs exosomes on excessive inflammation PMVECs injury. Results: We successfully isolated ADSCs exosomes, the characteristic of which were confirmed. ADSCs exosomes reduced excessive inflammatory response induced ROS accumulation and cell injury in PMVECs. Besides, ADSCs exosomes inhibited excessive inflammatory response induced ferroptosis while upregulated expression of GPX4 in PMVECs. And further GPX4 inhibition experiments revealed that ADSCs exosomes alleviated inflammatory response induced ferroptosis via upregulating GPX4. Meanwhile, ADSCs exosomes could increase the expression and nucleus translocation of Nrf2, while decrease the expression of Keap1. miRNA analysis and further inhibition experiments verified that specific delivery of miR-125b-5p by ADSCs exosomes inhibited Keap1 and alleviated ferroptosis. In CLP induced sepsis model, ADSCs exosomes could relieve the lung tissue injury and reduced the death rate. Besides, ADSCs exosomes alleviated oxidative stress injury and ferroptosis of lung tissue, while remarkably increase expression of Nrf2 and GPX4. Conclusion: Collectively, we illustrated a novel potentially therapeutic mechanism that miR-125b-5p in ADSCs exosomes could alleviate the inflammation induced PMVECs ferroptosis in sepsis induced acute lung injury via regulating Keap1/Nrf2/GPX4 expression, hence improve the acute lung injury in sepsis.

The use of artificial substrates and biofloc technology can favor fish culture and improve water quality. The aim of this study was to evaluate whether artificial substrates and carbon source additions modify the microbial activity of water bodies. The diversity and structure of microflora in the water after adding artificial substrates and carbon sources to the ponds were analyzed using high-throughput sequencing based on the V3-V4 region of 16S rRNA genes. The results showed that there was no difference in the richness and diversity of intestinal microflora between the control and experimental groups. Principal coordinate analysis (PCoA) and nonmetric multidimensional scaling (NMDS) showed that artificial substrate and carbon source addition changed the structure of the microflora. The results of a linear discriminant analysis (LDA) effect size (LefSe) indicated 11 biomarkers in the EGˍst group. Spearman correlation heatmap analysis showed that environmental factors affected the bacterial communities, and the results of a redundancy analysis indicated that chemical oxygen demand was a critical factor in controlling the bacterial communities in the water. These results provide an understanding of the effect of artificial substrate and carbon source addition on bacterial diversity and community composition in water.

In-situ three-dimensional (3D) bioprinting has been emerging as a promising technology designed to rapidly seal cutaneous defects according to their contour. Improvements in the formulations of multi-component bioink are needed to support cytocompatible encapsulation and biological functions. Platelet-rich plasma (PRP), as a source of patient-specific autologous growth factors, exhibits capabilities in tissue repair and rejuvenation. This study aimed to prepare PRP-integrated alginate-gelatin (AG) composite hydrogel bioinks and evaluate the biological effects in vitro and in vivo. 3D bioprinted constructs embedded with dermal fibroblasts and epidermal stem cells were fabricated using extrusion strategy. The integration of PRP not only improved the cellular behavior of seeded cells, but regulate the tube formation of vascular endothelial cells and macrophage polarization in a paracrine manner, which obtained an optimal effect at an incorporation concentration of 5%. For in-situ bioprinting, PRP integration accelerated the high-quality wound closure, modulated the inflammation and initiated the angiogenesis compared with the AG bioink. In conclusion, we revealed the regenerative potential of PRP, readily available at the bedside, as an initial signaling provider in multi-component bioink development. Combined with in-situ printing technology, it is expected to accelerate the clinical translation of rapid individualized wound repair.

The panel block is a quite important “intermediate product” in the shipbuilding process. However, the assembly efficiency of the panel block assembly line is not high. Therefore, rational scheduling optimization is of great significance for improving shipbuilding efficiency. Currently, the processing sequence of the panel blocks in the panel block assembly line is mainly determined using heuristic and metaheuristic algorithms. However, these algorithms have limitations, such as small problem-solving capacity and low computational efficiency. To address these issues, this study proposes an end-to-end approach based on deep reinforcement learning to solve the scheduling problem of the ship’s panel block assembly line. First, a Markov decision model is established, and a disjunctive graph is creatively used to represent the current scheduling status of the panel block assembly line. Then, a policy function based on a graph isomorphism network is designed to extract information from the disjunctive graph’s state and train it using Proximal Policy Optimization algorithms. To validate the effectiveness of our method, tests on both real shipbuilding data and publicly available benchmark datasets are conducted. We compared our proposed end-to-end deep reinforcement learning algorithm with heuristic algorithms, metaheuristic algorithms, and the unimproved reinforcement learning algorithm. The experimental results demonstrate that our algorithm outperforms other baseline methods in terms of model performance and computation time. Moreover, our model exhibits strong generalization capabilities for larger instances.

Harnessing the inflammation and angiogenesis is extremely important in wound healing. In this study, we developed bioactive elastin-based hydrogels which can recruit and modulate the innate immune cells and accelerate angiogenesis in the wound site and subsequently improve wound regeneration. These hydrogels were formed by visible-light cross-linking of acryloyl-(polyethylene glycol)-N-hydroxysuccinimide ester modified elastin with methacrylated gelatin, in order to mimic dermal microenvironment. These hydrogels showed highly tunable mechanical properties, swelling ratios and enzymatic degradation profiles, with moduli within the range of human skin. To mimic the in vivo degradation of the elastin by elastase from neutrophils, in vitro co-culture of the hydrogels and neutrophils was conducted. The derived conditioned medium containing elastin derived peptides (EDP-conditioned medium) promoted the expression of both M1 and M2 markers in M1 macrophages in vitro. Additionally, the EDP-conditioned medium induced superior tube formation of endothelia cells in Matrigel. In mice wound model, these elastin-based hydrogels attracted abundant neutrophils and predominant M2 macrophages to the wound and supported their infiltration into the hydrogels. The outstanding immunomodulatory effect of the elastin-based hydrogels resulted in superior angiogenesis, collagen deposition and dermal regeneration. Hence, these elastin-based hydrogels can be a promising regenerative platform to accelerate wound repair.

Keratins are a group of proteins that can constitute intermediate fibers. It is a component of the cytoskeleton and plays an important role in cell protection and structural support. Keratin 17, a Type I keratin, is a multifunctional protein that regulates a variety of biological processes, including cell growth, proliferation, migration, apoptosis and signal transduction. Abnormal expression of KRT17 is associated with a variety of diseases, such as skin diseases. In recent years, studies have shown that KRT17 is abnormally expressed in a variety of malignant tumours, such as lung cancer, cervical cancer, oral squamous cell carcinoma and sarcoma. These abnormal expressions are related to the occurrence, development and prognosis of malignant tumors. In this review, we summarized the expression patterns of KRT17 in a variety of malignant tumours, the role of KRT17 in the development and prognosis of different malignant tumors and its molecular mechanisms. We also discuss the potential clinical application of KRT17 as a valuable therapeutic target.

Glycogen storage disease type IV (GSD IV) is an ultra-rare autosomal recessive disease caused by variants in the GBE1 gene, which encodes the glycogen branching enzyme (GBE). GSD IV accounts for approximately 3% of all GSD. The phenotype of GSD IV ranges from neonatal death to mild adult-onset disease with variable hepatic, muscular, neurologic, dermatologic, and cardiac involvement. There is a paucity of literature and clinical and dietary management in GSD IV, and liver transplantation (LT) is described to correct the primary hepatic enzyme defect. Objectives: We herein describe five cases of patients with GSD IV with different ages of onset and outcomes as well as a novel GBE1 variant. Methods: This is a descriptive case series of patients receiving care for GSD IV at Reference Centers for Rare Diseases in Brazil and in the United States of America. Patients were selected based on confirmatory GBE1 genotypes performed after strong clinical suspicion. Results: Pt #1 is a Latin male with the chief complaints of hepatosplenomegaly, failure to thrive, and elevated liver enzymes starting at the age of 5 months. Before LT at the age of two, empirical treatment with corn starch (CS) and high protein therapy was performed with subjective improvement in his overall disposition and liver size. Pt #2 is a 30-month-old Afro-American descent patient with the chief complaints of failure to gain adequate weight, hypotonia, and hepatosplenomegaly at the age of 15 months. Treatment with CS was initiated without overall improvement of the symptoms. Pt #3.1 is a female Latin patient, sister to pt #3.2, with onset of symptoms at the age of 3 months with bloody diarrhea, abdominal distention, and splenomegaly. There was no attempt of treatment with CS. Pt #4 is an 8-year-old male patient of European descent who had his initial evaluation at 12 months, which was remarkable for hepatosplenomegaly, elevated ALT and AST levels, and a moderate dilatation of the left ventricle with normal systolic function that improved after LT. Pt #1, #3.2 and #4 presented with high levels of chitotriosidase. Pt #2 was found to have the novel variant c.826G > C p.(Ala276Pro). Conclusions: GSD IV is a rare disease with different ages of presentation and different cardiac phenotypes, which is associated with high levels of chitotriosidase. Attempts of dietary intervention with CS did not show a clear improvement in our case series.

3D cell culture technologies have recently shown very valuable promise for applications in regenerative medicine, but the most common 3D culture methods for mesenchymal stem cells still have limitations for clinical application, mainly due to the slowdown of inner cell proliferation and increase in cell death rate. We previously developed a new 3D culture of adipose-derived mesenchymal stem cells (ASCs) based on its self-feeder layer, which solves the two issues of ASC 3D cell culture on ultra-low attachment (ULA) surface. In this study, we compared the 3D spheroids formed on the self-feeder layer (SLF-3D ASCs) with the spheroids formed by using ULA plates (ULA-3D ASCs). We discovered that the cells of SLF-3D spheroids still have a greater proliferation ability than ULA-3D ASCs, and the volume of these spheroids increases rather than shrinks, with more viable cells in 3D spheroids compared with the ULA-3D ASCs. Furthermore, it was discovered that the SLF-3D ASCs are likely to exhibit the abovementioned unique properties due to change in the expression level of ECM-related genes, like COL3A1, MMP3, HAS1, and FN1. These results indicate that the SLF-3D spheroid is a promising way forward for clinical application.

Traditional aquaculture can cause serious environmental pollution. Biofilm and biofloc technology have the potential to limit aquaculture pollution. An outdoor experiment was conducted to evaluate the combined effects of eco-substrates and carbon addition on water quality, fish performance and nutrient budgets in the pond polyculture system. In the treatment group, the total ammonia nitrogen, nitrate nitrogen, nitrite nitrogen, and total nitrogen of the water were significantly lower compared to the control group (p < 0.05). The growth performance of H. molitrix and A. nobilis, including the final individual weight, specific growth rate, weight gain rate, total production and net production, was significantly higher in the treatment groups compared to the control (p < 0.05), while there was no significant difference in those of C. carpio between the two groups. Feed was the main N (>92%) and P (>95%) input during the experiment. Comprehensive accumulation was the main N (>58%) and P (>69%) output. The N and P feed input and comprehensive accumulation output declined in the treatment group. The N utilization efficiency in the experimental group increased slightly (p > 0.05), while the P utilization efficiency in the experimental group was significantly higher compared to the control (p < 0.05). Therefore, the application of eco-substrates and carbon addition can increase water quality, improve fish growth, and promote nutrient utilization efficiency in pond polyculture systems.

The effects of various levels of alkalinity stress (0, 18.25, 35.41, 52.53 and 69.74 mmol/L) in Chinese mitten crab (Eriocheir sinensis) were investigated by means of measuring hepatopancreas antioxidant system and serum nonspecific immune system-related indices at 0, 12, 24, 48 and 96 h, hepatopancreas tissue structure at 96 h. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and aspartate aminotransferase (AST) in each concentration group generally showed a trend of a first increasing and then decreasing during the 96-h stress process (p < 0.05), while no significant changes were observed in the blank group during this period (p > 0.05). The activities of CAT, GSH and AST in all treatment reached peak values at 24–48 h. At 96 h of alkalinity stress, the activities of GSH, alanine aminotransferase (ALT), acid phosphatise (ACP) and alkaline phosphatise (AKP) in the 18.25 mmol/L group were not significantly different with the control group (p > 0.05). The activities of SOD and CAT in the 52.53 and 69.74 mmol/L treatment were significantly lower than those in the control group (p < 0.05), and the level of total antioxidant capacity(T-AOC), ALT, ACP and AKP in the 69.74 mmol/L group were significantly higher than those in the other groups (p < 0.05). Hepatopancreatic histological observation showed that the hepatopancreas of E. sinensis in the control group was normal. With increasing alkalinity, the basal membrane of the hepatopancreas fell off or even ruptured. Additionally, the number of hepatopancreas vacuoles increased, the volume of B cells and their internal transport vesicles increased, epithelial cells disintegrated, and the nucleus gradually shrank. E. sinensis can activate antioxidant and nonspecific immune systems to adapt to alkalinity stress. However, oxidative stress, immune system damage and hepatopancreas structure damage were caused when the stress exceeded the adaptive capacity of the body.

Mitten crab, Eriocheir sensu stricto, is an important indigenous aquatic species and food source in Eastern Asia. Genetic diversity is an important prerequisite for the conservation and utilization of germplasm resources. However, the genetic diversity and differentiation of Eriocheir s. s. remains unclear. This study evaluated population genetic diversity and genetic differentiation of three Eriocheir s. s. populations from Suifenhe (SFH), Liaohe (LH), and Nanliujiang (NLJ), China, based on 19 microsatellite markers. The mean observed number of alleles (Na) was 22.84 alleles, and the mean polymorphism information content (PIC) was 0.86, which demonstrated high genetic diversity. The allele frequency distribution showed an “L” shape, ranging from 0.01 to 0.74. The genetic diversity parameter values of the LH population were higher than those of the other two populations. All pairwise FST values showed significant differences among the three Eriocheir s. s. populations (p < 0.01). The value of Nei’s genetic distance (DS) varied from 0.31 (between SFH and NLJ populations) to 0.33 (between SFH and LH populations). Overall, The results illustrate that the three wild Eriocheir s. s. populations have high genetic diversity and high genetic differentiation. This study provides the basis for Eriocheir s. s. utilization in China.

Four new polycyclic antibiotics, citreamicin θ A (1), citreamicin θ B (2), citreaglycon A (3), and dehydrocitreaglycon A (4), were isolated from marine-derived Streptomyces caelestis. The structures of these compounds were elucidated by 1D and 2D NMR spectra. All four compounds displayed antibacterial activity against Staphylococcus haemolyticus, Staphylococcus aureus, and Bacillus subtillis. Citreamicin θ A (1), citreamicin θ B (2) and citreaglycon A (3) also exhibited low MIC values of 0.25, 0.25, and 8.0 μg/mL, respectively, against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300.

Eleven new depsides—thielavins W–Z (1–4) and thielavins Z1–Z7 (5–11)—and also four known thielavins—A, H, J, and K (12–15)—were isolated from the ethyl acetate extract of a marine-derived fungal strain Thielavia sp UST030930-004. All of these compounds were evaluated for antifouling activity against cyprids of the barnacle Balanus (=Amphibalanus) amphitrite. The results showed that compounds 1–3 and 6–13 were active, with EC50 values ranging from 2.95 ± 0.59 to 69.19 ± 9.51 μM, respectively. The inhibitive effect of compounds 1–3 and 7 was reversible. This is the first description of the antifouling activity of thielavins against barnacle cyprids.