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The polyamide 12 (PA12) with different crystal forms is prepared with three crystallization paths. The crystal structures and corresponding thermal properties are systematically investigated. The results reveal that an α-form and a mixed (α + γ)-form of PA12 can be obtained by casting at 30°C and (40–80°C), respectively. Meanwhile, the γ-form of PA12 can be obtained by both casting at 90°C and slow melt cooling. However, the γ′-form is obtained only by melt quenching. Both the γ and γ′ forms of PA12 exhibit a single melting peak, whereas the α-form exhibits two melting peaks. The higher peak is attributed to the melting of γ-PA12, which originates from the melting–recrystallization of the α-PA12. It is found that the tensile properties of PA12 depend on the crystal forms. Both the γ and γ′-PA12 are strong and tough polymer materials, while α-PA12 is a strong but brittle polymer material.

The single-factor evaluation method, improved Nemerow index method, fuzzy mathematical synthesis evaluation method and comprehensive nutrient status index method were used to evaluate the water quality of the Zijiang River in summer, and to analyze the applicability of the evaluation methods. The results show that: (1) The Zijiang River is heavily polluted with nitrogen and TN is the main pollutant in the summer. The overall nutrient status index is 34.33, which is not eutrophic. (2) The single-factor evaluation method is simple and suitable for rapid identification of excessive pollutants, but cannot reflect the water quality. the Nemerow index method takes into account the weight of each evaluation factor in the river water quality, and is suitable for making a comprehensive evaluation of the river water quality, but has a certain degree of subjectivity when classifying the water quality. The fuzzy comprehensive evaluation method is suitable for reflecting the influence of different evaluation factors on water quality by calculating the weight and membership degree of each evaluation factor, but the calculation is complicated.The Integrated Nutrient Status Index method is suitable for determining whether eutrophication is occurring in a water body and cannot determine the water quality category.

Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for hematopoietic malignancies. Malnutrition is a common complication and negatively affects prognosis. Muscle mass has been shown to reflect the nutritional status of patients earlier than blood biochemical parameters such as albumin. However, the influence of pre-transplantation skeletal muscle mass (SMM) on the complications associated with early transplantation remains unclear. Objective To investigate the effect of pre-transplant SMM on the early outcomes of allo-HSCT, provide a clinical basis for nutritional interventions and prognosis improvement. Methods A study was conducted with 77 leukemia patients who underwent allo-HSCT at the Medical Center of Hematology, Xinqiao Hospital of Army Medical University from January to October 2022. Bioelectrical impedance analysis was used to assess skeletal muscle mass. The patients were divided into the normal SMM group of 36 cases and low SMM group of 41 cases according to their SMM. Baseline data, including personal and clinical details, were collected. Early post-transplant complications (within 30 days post-transplant) such as oral mucositis, gastrointestinal symptoms, infection and hematopoietic reconstitution time between the two groups were compared using SPSS 23.0 software. Results There was no statistically significant difference in the incidence of diarrhea, nausea, vomiting, and abdominal pain/gastritis incidence between the normal and low SMM groups (P>0.05). The incidence of oral mucositis, hypoalbuminemia, overt gastrointestinal bleeding, and infection was lower in the normal SMM group than in the low SMM group (P

Abstract Background Leptospira interrogans are bacterial pathogens of animal that cause zoonotic infections in human. Outer membrane proteins of leptospire are among the most effective antigens which can stimulate remarkable immune responses during the infection processes, and thus are currently considered leading candidate vaccine antigens. The objective of the present study is to predict and confirm major combined B and T cell epitopes of leptospiral outer membrane proteins OmpL1 and LipL41, as well as to evaluate their capacity in the induction of immune responses in BALB/c mice. Results In this study, four epitopes from OmpL1 and four from LipL41 conserved regions were evaluated for their potential utilization in leptospire vaccines. Firstly, combined B and T cell epitopes were predicted by softwares and expressed using a phage display system. OmpL1 residues 87-98 and 173-191 (OmpL187-98 and OmpL1173-191) and LipL4130-48, LipL41233-256 of LipL41 were identified as immunodominant B cell epitopes by Western blot. Epitopes OmpL1173-191, OmpL1297-320 of OmpL1 and LipL41233-256, LipL41263-282 of LipL41 were identified as immunodominant CD4+ T cell epitopes through proliferation analysis of splenocytes from recombinant OmpL1 (rOmpL1) or recombinant LipL41 (rLipL41)-immunized BALB/c (H-2d) mice. These epitopes induced responses of CD4+ T cells and Th1 (T helper cells) type cytokine responses during the infection. Conclusion This work identified combined T and B cell immunodominant epitopes in outer membrane proteins OmpL1 and LipL41 of Leptospira interrogans. OmpL1173-191 of OmpL1 and LipL41233-256 of LipL41 could be useful in a vaccine against Leptospira. The findings could also contribute to the development of effective cross-protective vaccine strategies for leptospirosis.

Abstract Background Variations of porB1A and porB1B genes and their serotypes exist in Neisseria gonorrhoeae isolates from different geographical areas, and some site mutations in the porB1B gene correlate with drug resistance. Methods The β-lactamase production of N. gonorrhoeae isolates was determined by paper acidometric test and nitrocefin discs. The porB1A and porB1B genes of 315 non-penicillinase-producting N. gonorrhoeae (non-PPNG) strains were amplified by PCR for sequencing to determine serotypes and site mutations. A duplex PCR was designed to simultaneously detect both porB1A and porB1B genes. Penicillin and tetracycline resistance was assessed by an in vitro drug sensitivity test. Results Of the N. gonorrhoeae isolates, 31.1% tested positive for porB1A and 68.9% for porB1B genes. All the 98 porB1A+ isolates belonging to IA6 serotype with either no mutation at the 120 and 121 sites (88.8%) or a D120G (11.2%) mutation and were no resistance to both penicillin and tetracycline. Among the 217 porB1B+ isolates, 26.7%, 22.6% and 11.5% belonged to IB3, IB3/6 and IB4 serotypes, respectively. Particularly, two novel chimeric serotypes, IB3/6-IB2 and IB2-IB4-IB2, were found in 77 and 8 porB1B+ isolates. Two hundred and twelve (97.7%) of the porB1B+ isolates were presented G120 and/or A121 mutations with 163 (76.9%) at both sites. Interestingly, within the 77 porB1B+ isolates belonging to IB3/6-IB2 serotype, 15 were discovered to possess novel deletions at both A121 and N122 sites. All the replacement mutations at these sites in PorB1B were correlated with resistance and the deletion mutation showed the highest resistance. Conclusion N. gonorrhoeae isolates circulating in Eastern China include a sole PorB1A serotype (IA6) and five PorB1B serotypes. Multiple mutations in porB1B genes, including novel A121 and N122 deletions, are correlated with high levels of penicillin and tetracycline resistance.

Abstract Background Pathogenic Leptospira species cause leptospirosis, a zoonotic disease of global importance. The spirochete displays active rotative mobility which may contribute to invasion and diffusion of the pathogen in hosts. FliY is a flagellar motor switch protein that controls flagellar motor direction in other microbes, but its role in Leptospira, and paricularly in pathogenicity remains unknown. Results A suicide plasmid for the fliY gene of Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai strain Lai that was disrupted by inserting the ampicillin resistance gene (bla) was constructed, and the inactivation of fliY gene in a mutant (fliY-) was confirmed by PCR and Western Blot analysis. The inactivation resulted in the mRNA absence of fliP and fliQ genes which are located downstream of the fliY gene in the same operon. The mutant displayed visibly weakened rotative motion in liquid medium and its migration on semisolid medium was also markedly attenuated compared to the wild-type strain. Compared to the wild-type strain, the mutant showed much lower levels of adhesion to murine macrophages and apoptosis-inducing ability, and its lethality to guinea pigs was also significantly decreased. Conclusion Inactivation of fliY, by the method used in this paper, clearly had polar effects on downstream genes. The phentotypes observed, including lower pathogenicity, could be a consequence of fliY inactivation, but also a consequence of the polar effects.

Most deaths in breast cancer patients are attributed to metastasis, and lung metastasis is associated with a particularly poor prognosis; therefore it is imperative to identify potential target for intervention. The transforming growth factor‐β (TGF‐β) pathway plays a vital role in breast cancer metastasis, in which Smad3 is the key mediator and performs specific functions by binding with different cofactors. However, Smad3 cofactors involved in lung metastasis have not yet been identified. This study first establishes the interactome of Smad3 in breast cancer cells and identifies ZNF8 as a novel Smad3 cofactor. Furthermore, the results reveal that ZNF8 is closely associated with breast cancer lung metastasis prognosis, and specifically facilitates TGF‐β pathway‐mediated breast cancer lung metastasis by participating in multiple processes. Mechanistically, ZNF8 binds with Smad3 to enhance the H3K4me3 modification and promote the expression of lung metastasis signature genes by recruiting SMYD3. SMYD3 inhibition by BCI121 effectively prevents ZNF8‐mediated lung metastasis. Overall, the study identifies a novel cofactor of TGF‐β/Smad3 that promotes lung metastasis in breast cancer and introduces potential therapeutic strategies for the early management of breast cancer lung metastasis. [ABSTRACT FROM AUTHOR]

PROTAC is a rapidly developing engineering technology for targeted protein degradation using the ubiquitin–proteasome system, which has promising applications for inflammatory diseases, neurodegenerative diseases, and malignant tumors. This paper gives a brief overview of the development and design principles of PROTAC, with a special focus on PROTAC-based explorations in recent years aimed at achieving controlled protein degradation and improving the bioavailability of PROTAC, as well as TPD technologies that use other pathways such as autophagy and lysosomes to achieve targeted protein degradation. [ABSTRACT FROM AUTHOR]

Auxetic re-entrant honeycomb (AREH) structures, consisting of a single soft or tough material, have long faced the challenge of balancing stiffness and rebound resilience. To achieve this balance, dual-material printing technology is employed to enhance shock absorption by combining layers of soft and tough materials. Additionally, a novel structure called the curved re-entrant honeycomb (CREH) structure has been introduced to improve stiffness. The selected materials for processing the composite structures of AREH and CREH are the rigid thermoplastic polymer polylactic acid (PLA) and the soft rubber material thermoplastic polyurethane (TPU), created utilizing fused deposition modeling (FDM) 3D printing technology. The influence of the material system and structure type on stress distribution and mechanical response was subsequently investigated. The results revealed that the dual-material printed structures demonstrated later entry into the densification phase compared to the single-material printed structures. Moreover, the soft material in the interlayer offered exceptional protection, thereby ensuring the overall integrity of the structure. These findings effectively serve as a reference for the design of dual-material re-entrant honeycombs. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) accounts for over 80% of cases among liver cancer, with high incidence and poor prognosis. Thus, it is of valuable clinical significance for discovery of potential biomarkers and drug targets for HCC. In this study, based on proteomics data analysis, really interesting new gene (RING) finger protein 149 (RNF149) was found to be elevated in hepatocellular carcinoma (HCC) tissues and associated with HCC malignancy, which was validated by immunohistochemistry (IHC) staining. RNF149 was demonstrated to promote proliferation, migration, and invasion of HCC cells dependent on its E3 ubiquitin ligase activity in vitro, and further bioinformatics analysis indicated that high expression of RNF149 correlated with immunosuppressive tumor microenvironment (TME). These results suggest that RNF149 could exert protumor functions in HCC in dependence of its E3 ubiquitin ligase activity, and might be a potential prognostic marker and therapeutic target for HCC treatment. Hepatocellular carcinoma (HCC) accounts for over 80% of cases among liver cancer, with high incidence and poor prognosis. Thus, it is of valuable clinical significance for discovery of potential biomarkers and drug targets for HCC. In this study, based on the proteomic profiling data of paired early-stage HCC samples, we found that RNF149 was strikingly upregulated in tumor tissues and correlated with poor prognosis in HCC patients, which was further validated by IHC staining experiments of an independent HCC cohort. Consistently, overexpression of RNF149 significantly promoted cell proliferation, migration, and invasion of HCC cells. We further proved that RNF149 stimulated HCC progression via its E3 ubiquitin ligase activity, and identified DNAJC25 as its new substrate. In addition, bioinformatics analysis showed that high expression of RNF149 was correlated with immunosuppressive tumor microenvironment (TME), indicating its potential role in immune regulation of HCC. These results suggest that RNF149 could exert protumor functions in HCC in dependence of its E3 ubiquitin ligase activity, and might be a potential prognostic marker and therapeutic target for HCC treatment. [ABSTRACT FROM AUTHOR]

Osteoarthritis caused by articular cartilage defects is a particularly common orthopedic disease that can involve the entire joint, causing great pain to its sufferers. A global patient population of approximately 250 million people has an increasing demand for new therapies with excellent results, and tissue engineering scaffolds have been proposed as a potential strategy for the repair and reconstruction of cartilage defects. The precise control and high flexibility of 3D printing provide a platform for subversive innovation. In this perspective, cartilage tissue engineering (CTE) scaffolds manufactured using different biomaterials are summarized from the perspective of 3D printing strategies, the bionic structure strategies and special functional designs are classified and discussed, and the advantages and limitations of these CTE scaffold preparation strategies are analyzed in detail. Finally, the application prospect and challenges of 3D printed CTE scaffolds are discussed, providing enlightening insights for their current research. [ABSTRACT FROM AUTHOR]

Soft robots have drawn a lot of attention due to their soft materials that make them highly flexible and adaptable to complex environments. However, these also make soft robots not suited to high-load tasks, and achieving controllable material stiffness variation is still a challenge. Herein, we designed a soft structure with variable stiffness based on electrorheological fluids, which presented the advantages of continuously variable stiffness and fast response. The structure exhibited a stiffness of up to 1065 mN mm−1 when the electric field strength was 4.5 kV mm−1 (displacement of 1 mm). When varying the electric field strength (0 to 4.5 kV mm−1), the rate of stiffness variation was over 1500%. According to the load cycle experiments, it was shown that the structure's response time to a change in load was less than 65 ms, and that the structure changes could be made repeatedly. In addition, we demonstrated the functions of stiffness adjustment, shape memory, and motion locking of the structure. This work has potential applications in the fields of soft robotics and artificial muscles. [ABSTRACT FROM AUTHOR]

Omics data from clinical samples are the predominant source of target discovery and drug development. Typically, hundreds or thousands of differentially expressed genes or proteins can be identified from omics data. This scale of possibilities is overwhelming for target discovery and validation using biochemical or cellular experiments. Most of these proteins and genes have no corresponding drugs or even active compounds. Moreover, a proportion of them may have been previously reported as being relevant to the disease of interest. To facilitate translational drug discovery from omics data, we have developed a new classification tool named O mics and T ext driven T ranslational M edicine (OTTM). This tool can markedly narrow the range of proteins or genes that merit further validation via drug availability assessment and literature mining. For the 4489 candidate proteins identified in our previous proteomics study, OTTM recommended 40 FDA-approved or clinical trial drugs. Of these, 15 are available commercially and were tested on hepatocellular carcinoma Hep-G2 cells. Two drugs—tafenoquine succinate (an FDA-approved antimalarial drug targeting CYC1) and branaplam (a Phase 3 clinical drug targeting SMN1 for the treatment of spinal muscular atrophy)—showed potent inhibitory activity against Hep-G2 cell viability, suggesting that CYC1 and SMN1 may be potential therapeutic target proteins for hepatocellular carcinoma. In summary, OTTM is an efficient classification tool that can accelerate the discovery of effective drugs and targets using thousands of candidate proteins identified from omics data. The online and local versions of OTTM are available at http://otter-simm.com/ottm.html. [ABSTRACT FROM AUTHOR]

Disseminated ankle mycosis is a life-threatening systemic infection caused by the emerging opportunistic and lethal fungal pathogen Talaromyces marneffei which is more common in HIV-positive patients. However, an increasing number of infections are occurring in HIV-negative patients. Here, we report a case of Talaromyces marneffei infection in HIV-negative patient. A 50s HIV-negative male patient with fever, cough, bloody sputum expectoration, pulmonary sarcoidosis and body rashes was hospitalized at Zhejiang Provincial People's Hospital. CT scanning showed pulmonary multiple nodules with apical bronchial occlusion, patchy infiltration and pathological biopsy demonstrated bronchiolitis obliterans with organized pneumonia and chronic active inflammation of lung tissue with infiltration of numerous lymphocytes, plasma cells, phagocytes and neutrophils. Laboratory tests revealed significantly increased white blood cells count 18.3 × 109/L, neutrophil count 15.34 × 109/L, monocyte count 0.66 × 109/L, platelet count 517 × 109/L, C-reactive protein 116 mg/L, erythrocyte sedimentation rate 112mm/h. The β-D-glucan test was negative (33.06 pg/mL) while fungal culture of broncho alveolar lavage fluid revealed colonies with temperature-dependent dimorphic growth character and Talaromyces marneffei was confirmed by ITS sequencing of the colonies. The patient exhibited radiological improvement and clinical recuperation after intravenously guttae of voriconazole. Talaromycosis in immunocompetent and HIV-negative individuals is relatively rare and is characterized by an insidious onset, various clinical manifestations, and is clinically challenging. Fungal culture and ITS sequencing are warranted for diagnosis Talaromyces marneffei infection. This is the first report on identification of Talaromyces marneffei infection in an HIV-negative patient with skin involvement by ITS sequencing in Zhejiang. [ABSTRACT FROM AUTHOR]

As an effective technique for fabricating conductive and thermally conductive polymer composites, a multi-filler system incorporates different types and sizes of multiple fillers to form interconnected networks with improved electrical, thermal, and processing properties. In this study, DIW forming of bifunctional composites was achieved by controlling the temperature of the printing platform. The study was based on enhancing the thermal and electrical transport properties of hybrid ternary polymer nanocomposites with multi-walled carbon nanotubes (MWCNTs) and graphene nanoplates (GNPs). With thermoplastic polyurethane (TPU) used as the matrix, the addition of MWCNTs, GNPs and both mixtures further improved the thermal conductivity of the elastomers. By adjusting the weight fraction of the functional fillers (MWCNTs and GNPs), the thermal and electrical properties were gradually explored. Here, the thermal conductivity of the polymer composites increased nearly sevenfold (from 0.36 W·m−1·k−1 to 2.87 W·m−1·k−1) and the electrical conductivity increased up to 5.49 × 10−2 S·m−1. It is expected to be used in the field of electronic packaging and environmental thermal dissipation, especially for modern electronic industrial equipment. [ABSTRACT FROM AUTHOR]

A majority of biological organisms in nature can adjust their biomechanical energy to adapt to complex environments, but most of the current synthetic composites have limited rigid and flexible states that cannot achieve multi-level and continuous regulation on altering mechanical stiffness. Herein, a direct ink printing (DIW) approach for forming a 4D printable phase-changing elastomer that achieves multiple stable stages in response to a thermal stimulus has been developed. This composite consists of low melting point alloy (LMPA) microparticles incorporated into a silicone elastomer (PDMS) using a facile composite manufacturing process. The particles with different melting points amplify the steady stage in flexural modulus under a thermal stimulus, which is desirable for stiffness-changing applications, particularly relevant to soft robotics. Moreover, the composites exhibit improved printability for three-dimensional direct printing via adjusting the volume ratio of the raw materials, which circumvents the dilemma that most sample structures are restricted between one- and two-dimensional transformations and the conventional craftsmanship is limited by complex production. It is demonstrated as well that the utility of LMPA/PDMS composites has an advantage of multiple stiffness changes at the set-transition temperature for unveiling their brilliant prospects for soft actuators with 4D printing technology. [ABSTRACT FROM AUTHOR]