An Injectable Photothermal-Fusing Hydrogel: Achieving Temperature-Controllable Mild Photothermal Therapy to Reverse Chemotherapy-Induced Immune Tolerance.

Mild photothermal therapy (M-PTT) can induce immunogenic cell death (ICD) to reverse the immune tolerance caused by low-dose chemotherapy. However, it still needs convenient strategies to control temperature during M-PTT. In this work, the phase change material lauric acid (LA, melting point 43 °C) was introduced to construct nanoparticles loaded with deferoxamine mesylate (DFO) and cisplatin (CDDP), which were mixed into a supramolecular hydrogel formed by polyvinylpyrrolidone (PVP)/tannic acid (TA)/Fe3+ to obtain FeTP@DLD/DLC. When the temperature reached 43 °C under laser irradiation, DFO was released from melted LA and destroyed the interaction between Fe3+ and TA to cut off the temperature increase, achieving a "photothermal fusing effect". Meanwhile, CDDP was released for low-dose chemotherapy, while the resulting immune tolerance was reversed by M-PTT-induced ICD. Finally, through a single administration, FeTP@DLD/DLC-mediated M-PTT synergized with chemotherapy achieved a potent antitumor effect. This work provided a convenient solution for the revitalization of these traditional antitumor therapies.

Construction of MXene-mediated inorganic-organic quaternary ammonium salt-hybrid coating for fire safety and multi-mode synergistic antibacterial of cotton fabric.

With the continuous development of the society, there is a growing demand for the durability, versatility and multifunction of cott fabrics. In this work, the cotton fabric is coated with multifunctional coating via dip-coating of transition metal carbide (MXene) and then encapsulation of dimethyloctadecyl [3-trimethoxysilopropyl] ammonium chloride (QAS). In view of MXene with excellent light absorption and photothermal conversion efficiency, the controllable antibacterial performance of the cotton fabric is further improved. Benefiting from the encapsulation of QAS, CF@P@M@QAS fabric shows mechanical stability (24 h washing, 1000 cycles folding test and 100 cyclic abrasion) and hydrophobicity. Meantime, the QAS on the surface of multifunctional cotton fabric significantly increases antibacterial activity, and the antibacterial rate can reach to 100 % against Staphylococcus aureus (S. aureus) and 98 % Escherichia coli (E. coli). Besides, CF@P@M@QAS cotton fabric also integrates functions of fire safety and physical therapy. Thus, this multifunctional cotton fabric based MXene offers a novel solution for extending its application in medical electronics and physical therapy.

Self-Supplied Reactive Oxygen Species-Responsive Mitoxantrone Polyprodrug for Chemosensitization-Enhanced Chemotherapy under Moderate Hyperthermia.

Currently, the secondary development and modification of clinical drugs has become one of the research priorities. Researchers have developed a variety of TME-responsive nanomedicine carriers to solve certain clinical problems. Unfortunately, endogenous stimuli such as reactive oxygen species (ROS), as an important prerequisite for effective therapeutic efficacy, are not enough to achieve the expected drug release process, therefore, it is difficult to achieve a continuous and efficient treatment process. Herein, a self-supply ROS-responsive cascade polyprodrug (PMTO) is designed. The encapsulation of the chemotherapy drug mitoxantrone (MTO) in a polymer backbone could effectively reduce systemic toxicity when transported in vivo. After PMTO is degraded by endogenous ROS of the TME, another part of the polyprodrug backbone becomes cinnamaldehyde (CA), which can further enhance intracellular ROS, thereby achieving a sustained drug release process. Meanwhile, due to the disruption of the intracellular redox environment, the efficacy of chemotherapy drugs is enhanced. Finally, the anticancer treatment efficacy is further enhanced due to the mild hyperthermia effect of PMTO. In conclusion, the designed PMTO demonstrates remarkable antitumor efficacy, effectively addressing the limitations associated with MTO.

A Structural Systems Biology Approach to High-Risk CG23 Klebsiella pneumoniae.

Klebsiella pneumoniae is a leading cause of antibiotic-resistant-associated deaths in the world. Here, we report the deposition of 14 structures of enzymes from both the core and accessory genomes of sequence type 23 (ST23) K1 hypervirulent K. pneumoniae.

Distribution characteristics of microplastics in storm-drain inlet sediments affected by the types of urban functional areas, economic and demographic conditions in southern Beijing.

A storm-drain inlet is an important link in the transport of microplastic pollutants in urban rainwater runoff. In three functional districts (agricultural, commercial, and residential) from Beijing South 2nd Ring Road to South 6th Ring Road, microplastics in storm-drain inlet sediments were analyzed for abundance and characteristics. The abundance of microplastics in the collected samples ranged from 1121 ± 247 items kg-1 to 7393 ± 491 items kg-1. Among the sample areas, the commercial area had the greatest abundance (11094 items kg-1), while the agricultural area had the lowest (833 items kg-1). The microplastics in the samples were mainly fragments, accounting for 50.4%. Microplastics of less than 1 mm accounted for 74.8%. The color of microplastics was diverse, with colored MPs accounting for 26% and transparent ones for 47.8%. Most of the polymers detected were PET, PS, and PP, which are the most commonly used polymers. Overall, the results provide baseline data on microplastic pollution and its associated risks, in addition to guidelines for controlling runoff pollution.

Biochemical and structural studies of two tetrameric nucleoside 2'-deoxyribosyltransferases from psychrophilic and mesophilic bacteria: Insights into cold-adaptation.

Nucleoside 2'-deoxyribosyltransferases (NDTs) catalyze the cleavage of glycosidic bonds of 2'-deoxynucleosides and the following transfer of the 2'-deoxyribose moiety to acceptor nucleobases. Here, we report the crystal structures and biochemical properties of the first tetrameric NDTs: the type I NDT from the mesophilic bacterium Enterococcus faecalis V583 (EfPDT) and the type II NDT from the bacterium Desulfotalea psychrophila (DpNDT), the first psychrophilic NDT. This novel structural and biochemical data permitted an exhaustive comparative analysis aimed to shed light into the basis of the high global stability of the psychrophilic DpNDT, which has a higher melting temperature than EfPDT (58.5 °C versus 54.4 °C) or other mesophilic NDTs. DpNDT possesses a combination of unusual structural motifs not present neither in EfPDT nor any other NDT that most probably contribute to its global stability, in particular, a large aliphatic isoleucine-leucine-valine (ILV) bundle accompanied by a vicinal disulfide bridge and also an intersubunit disulfide bridge, the first described for an NDT. The functional and structural features of DpNDT do not fit the standard features of psychrophilic enzymes, which lead us to consider the implication of (sub)cellular levels together with the protein level in the adaptation of enzymatic activity to low temperatures.

Ratio-Adjustable Upconversion Luminescence Nanoprobe for Ultrasensitive In Vitro Diagnostics.

The development of precise medicine requires diagnostic probes to simultaneously satisfy an excellent detection limit and a wide linear analysis range because of enormous individual-discrepancy of disease biomarker concentrations, yet it remains challenging. Herein, an upconverison nanoprobe with a luminescence ratio flexibly tailored was designed for ultrasensitive monitoring exhaled nitric oxide to indicate the clinical course of asthma. Two independent emissions from the same nanoprobe can be discretionarily modulated to vary their intensity ratios for adapting different analysis requirements. Delightfully, this novel nanoprobe demonstrated a 100-fold lower detection limit compared with the traditional ratiometric fluorescence manner and a more broad linear detection range from the subpart per billion (ppb) level to hundreds of ppb. This ratio-adjustable fluorescence detection strategy holds great potential for miscellaneous disease diagnosis applications.

Sensor Domain of Histidine Kinase VxrA of Vibrio cholerae- A Hairpin-swapped Dimer and its Conformational Change.

VxrA and VxrB are cognate histidine kinase (HK) - response regulator (RR) pairs of a two-component signaling system (TCS) found in Vibrio cholerae, a bacterial pathogen that causes cholera. The VxrAB TCS positively regulates virulence, the Type VI Secretion System, biofilm formation, and cell wall homeostasis in V. cholerae, providing protection from environmental stresses and contributing to the transmission and virulence of the pathogen. The VxrA HK has a unique periplasmic sensor domain (SD) and, remarkably, lacks a cytoplasmic linker domain between the second transmembrane helix and the dimerization and histidine phosphotransfer (DHp) domain, indicating that this system may utilize a potentially unique signal sensing and transmission TCS mechanism. In this study, we have determined several crystal structures of VxrA-SD and its mutants. These structures reveal a novel structural fold forming an unusual ß hairpin-swapped dimer. A conformational change caused by relative rotation of the two monomers in a VxrA-SD dimer could potentially change the association of transmembrane helices and, subsequently, the pairing of cytoplasmic DHp domains. Based on the structural observation, we propose a putative scissor-like closing regulation mechanism for the VxrA HK.IMPORTANCE V. cholerae has a dynamic life cycle, which requires rapid adaptation to changing external conditions. Two-component signal transduction (TCS) systems allow V. cholerae to sense and respond to these environmental changes. The VxrAB TCS positively regulates a number of important V. cholerae phenotypes, including virulence, the Type Six Secretion System, biofilm formation, and cell wall homeostasis. Here, we provide the crystal structure of the VxrA sensor histidine kinase sensing domain and propose a mechanism for signal transduction. The cognate signal for VxrAB remains unknown, however, in this work we couple our structural analysis with functional assessments of key residues to further our understanding of this important TCS.

The Diagnostic Value of Serum Ferritin for Telogen Effluvium: A Cross-Sectional Comparative Study.

PURPOSE: This study aimed to explore the relationship between serum ferritin levels and telogen effluvium. PATIENTS AND METHODS: A total of 193 telogen effluvium patients and 104 female androgenetic alopecia patients were included. We collected the test result of serum ferritin levels, compared with the results of 183 healthy subjects. Receiver Operator Characteristic curves were generated to assess the potential diagnostic value of serum ferritin in telogen effluvium patients. RESULTS: The serum ferritin in telogen effluvium patients were significantly lower than that in the healthy control group (P = 0.000) or female androgenetic alopecia patients (P =0.000). Patients with lower serum ferritin levels got high odds to have telogen effluvium. The areas under the Receiver Operator Characteristic curve of serum ferritin levels were 0.735 and 0.645 for distinguishing telogen effluvium patients from healthy control subjects or female androgenetic alopecia patients. CONCLUSION: Serum ferritin could be a potential biomarker for clinical diagnosis of telogen effluvium.

Innovative use of concentrated growth factors combined with corticosteroids to treat discoid lupus erythematosus alopecia: A case report.

Alopecia for patients with discoid lupus erythematosus can sometimes be a refractory condition, where mixed infiltrates of T lymphocytes and histiocytes leads to destruction of hair follicles, which might cause permanent scarring. Early diagnosis and timely treatment can achieve hair regeneration and prevent further disease progression. Concentrated growth factor, a novel autologous plasma extract, contains various growth factors that could promote tissue regeneration. In this article, we report a case of cell growth factor combined with corticosteroids for the treatment of discoid lupus erythematosus alopecia. This case study concludes with satisfactory clinical effect.

Acceleration of soil salinity accumulation and soil degradation due to greenhouse cultivation: a survey of farmers' practices in China.

Soil environment and water quality face large pressure due to the rapid expansion of greenhouse cultivation in China. However, studies rarely provide the linkage between farmers' practices and soil degradation in greenhouse cultivation field. In this study, a field survey and sampling of greenhouse cultivation soil were conducted in five regions of China to investigate the accumulation and variation characteristics of soil ion compositions in the field. First, the pH, ion compositions, and electrical conductivity (EC) of 132 composite soil samples were analyzed. Second, farmers' practices with regard to fertilizer, crop yield, and soil degradation processes were surveyed. Lastly, soil nutrient status was evaluated by different grades, and the principal component analysis method was used to analyze the main sources of soil ion compositions. Results of the study reveal the following: (1) Enrichment of greenhouse soil nutrient was mainly caused by excessive fertilization, which introduced the secondary salinization phenomenon for 3-5 years in plastic greenhouse and 1-3 years in multispan greenhouse. (2) Significant changes between the EC and salt ion composition of open soil and greenhouse cultivated soil were observed. The contents of nitrate nitrogen and ammonium nitrogen in the greenhouse soil were high. (3) After a certain period of cultivation in the greenhouse, salt accumulation, pH decline, and varying degrees of acidification were observed in the soil profile. The relationship between soil pH and EC values indicated that the balance of soil compositions was broken. The recommended methods for sustaining greenhouse cultivation include balanced fertilization, rotation practices, and reasonable water utilization in the field.

Multi-stage surgery combined with radiotherapy for treatment of giant anterior chest wall keloid: A case report.

RATIONALE: Giant keloids often have indications for surgical resection, but postoperative reconstruction of the skin and high recurrence of keloids are a challenge for clinical treatment. This article reports a rare successful treatment of a giant keloid in the anterior chest wall by multistage surgery combined with radiotherapy, which is why this case is meaningful. PATIENT CONCERNS: A 66-year-old woman presented a giant keloid with ulcerations and severe itching on the anterior chest wall. She had a history of keloid disease for more than 10 years, and had been treated by multiple operations, with no success. DIAGNOSES: The patient was diagnosed as keloid based on her history and symptoms. Histopathology findings supported our diagnosis. INTERVENTIONS: We successfully excised the keloid after 5 operations and 2 rounds of electron-beam radiotherapy, which was applied at 24 hours after the 4th and 5th operation. OUTCOMES: There was no sign of recurrence over the follow-up period of 24 months. LESSONS: The combination of multistage surgery and radiotherapy presents as a good choice for the treatment of giant keloids.

Structures of teixobactin-producing nonribosomal peptide synthetase condensation and adenylation domains.

The recently discovered antibiotic teixobactin is produced by uncultured soil bacteria. The antibiotic inhibits cell wall synthesis of Gram-positive bacteria by binding to precursors of cell wall building blocks, and therefore it is thought to be less vulnerable to development of resistance. Teixobactin is synthesized by two nonribosomal peptide synthetases (NRPSs), encoded by txo1 and txo2 genes. Like other NRPSs, the Txo1 and Txo2 synthetases are large, multifunctional, and comprised of several modules. Each module is responsible for catalysis of a distinct step of teixobactin synthesis and contains specific functional units, commonly including a condensation (C) domain, an adenylation (A) domain, and a peptidyl carrier protein (PCP) domain. Here we report the structures of the C-A bidomains of the two L-Ser condensing modules, from Txo1 and Txo2, respectively. In the structure of the C domain of the L-Ser subunit of Txo1, a large conformational change is observed, featuring an outward swing of its N-terminal α-helix. This repositioning, if functionally validated, provides the necessary conformational change for the condensation reaction in C domain, and likely represents a regulatory mechanism. In an Acore subdomain, a well-coordinated Mg2+ cation is observed, which is required in the adenylation reaction. The Mg2+-binding site is defined by a largely conserved amino acid sequence motif and is coordinated by the α-phosphate group of AMP (or ATP) when present, providing some structural evidence for the role of the metal cation in the catalysis of A domain.

Upconversional Nanoprobes with Highly Efficient Energy Transfer for Ultrasensitive Detection of Alkaline Phosphatase.

Sensitive detection of alkaline phosphatase (ALP) activity in human serum is important for diagnosis of various diseases. In this work, a novel sandwich-structured upconversion nanoparticle, NaYF4:Yb/Er@NaErF4@NaYF4, is fabricated to construct an upconversional nanoprobe for ultrasensitive detection of phosphate and ALP activity. The inner shell of NaErF4 bridges the emitters in the core with the external luminescence quenchers to greatly improve the energy transfer efficiency. The quencher, herein, is a coordination complex formed between sulfosalicylic acid and ferric ions. Owing to the higher affinity for phosphate, ferric ions dissociate from the complex and potently combine with phosphate ions, thus interrupting the energy transfer process and recovering the luminescence. This upconversional nanoprobe shows rapid and sensitive detection of phosphate with a limit of detection of 2.5 nM. Because ALP catalyzes the hydrolysis of p-nitrophenyl phosphate to form p-nitrophenol and inorganic phosphate ions, the nanoprobe is further utilized to achieve sensitive detection of ALP with a limit of detection of 0.5 µU/mL. This novel strategy offers a new opportunity for developing sensitive upconversional nanoprobes and many other energy transfer-based applications.

Zearalenone exposure elevated the expression of tumorigenesis genes in mouse ovarian granulosa cells.

Zearalenone (ZEA) is one of mycotoxins which are from corn, sorghum and wheat. As an estrogenic compound, ZEA mainly affects animal growth and reproduction with causing abnormal reproduction capability. Previous studies have shown that ZEA poses adverse effects on follicular development, but the mechanism of genetic toxicity of ZEA is not understood. The purpose of this study was to explore the effects of ZEA exposure on granulosa cells which play vital roles during follicular development. Mouse granulosa cells were exposed to 10 µM or 30 µM ZEA for 72 h in vitro, and the differences in gene expression patterns between control and ZEA exposures were analyzed by RNA-seq. The data demonstrated that 30 µM ZEA had a significant effect on the gene expression, especially ZEA exposure increased the expression of many genes related to different kinds of cancers and cancer related pathways like Hippo signaling pathway and the related genes, such as Ccnd1, Smad3, Tead3, Yap1 and Wwtr1. Furthermore, immunohistochemistry confirmed the increase in the protein levels of YAP1, WWTR1 and CCND1 in 30 µM ZEA exposure group. Collectively, this investigation indicated that ZEA exposure promoted the expression of tumorigenesis genes in mouse granulosa cells to.

Starvation during pregnancy impairs fetal oogenesis and folliculogenesis in offspring in the mouse.

Although it is becoming increasingly evident that maternal starvation during pregnancy can have permanent effects on a range of physiological processes in the offspring, scant information is available about the consequence of such condition for oogenesis and hence for lifetime reproductive success of progeny in mammals. In the present study, we address this topic by starving pregnant mice at the time of ovarian differentiation (12.5 days post coitum (dpc)) for three consecutive days and analyzed the consequence first on the survival of the fetal oocytes and their capability to progress throughout the stages of meiotic prophase I (MPI) and then on the postnatal folliculogenesis of the offspring. The results showed that maternal starvation increased apoptosis in the fetal ovaries, resulting in reduction of the oocyte number. Moreover, MPI progression was slowed down in the surviving oocytes and the expression of DNA repair players in the starved ovaries increased. Transcriptome analysis identified 61 differentially expressed genes between control and starved ovaries, the most part of these being involved in metabolic processes. A significant decrease in the percentage of oocytes enclosed in primordial follicles and the expression of oocyte genes critically involved in folliculogenesis such as Nobox, Lhx8 and Sohlh2 in the 3 days post partum (dpp) starved ovaries were found. Finally, at the time of juvenile period (21 dpp), the number of oocytes and antral follicles resulted significantly lower in the ovaries of the offspring from starved mothers in comparison to controls. Our findings support the notion that maternal starvation can affect ovary development in the offspring that could adversely affect their reproductive success in the adult life.

Molecular control of gene expression by Brucella BaaR, an IclR-type transcriptional repressor.

The general stress response sigma factor σE1 directly and indirectly regulates the transcription of dozens of genes that influence stress survival and host infection in the zoonotic pathogen Brucella abortus Characterizing the functions of σE1-regulated genes therefore would contribute to our understanding of B. abortus physiology and infection biology. σE1 indirectly activates transcription of the IclR family regulator Bab2_0215, but the function of this regulator remains undefined. Here, we present a structural and functional characterization of Bab2_0215, which we have named B rucella adipic acid-activated regulator (BaaR). We found that BaaR adopts a classic IclR-family fold and directly represses the transcription of two operons with predicted roles in carboxylic acid oxidation. BaaR binds two sites on chromosome II between baaR and a divergently transcribed hydratase/dehydrogenase (acaD2), and it represses transcription of both genes. We identified three carboxylic acids (adipic acid, tetradecanedioic acid, and ϵ-aminocaproic acid) and a lactone (ϵ-caprolactone) that enhance transcription from the baaR and acaD2 promoters. However, neither the activating acids nor caprolactone enhanced transcription by binding directly to BaaR. Induction of baaR transcription by adipic acid required the gene bab2_0213, which encodes a major facilitator superfamily transporter, suggesting that Bab2_0213 transports adipic acid across the inner membrane. We conclude that a suite of structurally related organic molecules activate transcription of genes repressed by BaaR. Our study provides molecular-level understanding of a gene expression program in B. abortus that is downstream of σE1.