Cellulose Nanofiber-Based Triboelectric Nanogenerators for Efficient Air Filtration in Harsh Environments.

Advanced portable healthcare devices with high efficiencies, small pressure drops, and high-temperature resistance are urgently desired in harsh environments with high temperatures, high humidities, and high levels of atmospheric pollution. Triboelectric nanogenerators (TENGs), which serve as energy converters in a revolutionary self-powered sensor device, present a sustainable solution for meeting these requirements. In this work, we developed a porous negative triboelectric material by synthesizing ZIF-8 on the surface of a cellulose/graphene oxide aerogel, grafting it with trimethoxy(1H,1H,2H,2H-heptadecafluorodecyl)silane, and adding a negative corona treatment, and it was combined with a positive triboelectric material to create a cellulose nanofiber-based TENG self-powered filter. The devices achieved a balance between a small pressure drop (53 Pa) and high filtration efficiency (98.97%, 99.65%, and 99.93% for PM0.3, PM0.5, and PM1, respectively), demonstrating robust filtration properties at high temperatures and high humidities. Our work provides a new approach for developing self-powered wearable healthcare devices with excellent air filtration properties.

Facile and Ultrasensitive Food Allergen Quantification Using Microzone Paper-Based Mass Spectrometric Immunoassay.

Highly sensitive and rapid measurement of food allergens is essential to avoid unanticipated food allergies and to determine whether cross-contamination occurs in the food industry. Commercial immunoassay kits offer high specificity and convenience for allergen detection but still suffer limited quantitative sensitivity, accuracy, and stability based on the optical readout. In this work, a paper-based mass spectrometric immunoassay platform was constructed to achieve facile and highly sensitive quantification of peanut allergen, which combined the advantages of good specificity and accurate quantification from mass spectrometry and simplicity from a paper-based immunoassay. In this platform, a novel quaternary ammonium-based mass tag and a paper chip with a microzone were designed and developed, contributing to a large signal enhancement. This method was able to detect Ara h1 with a linear range of 0.1-100 ng mL-1 and a detection limit of 0.08 ng mL-1 in milk matrices. It has also been successfully applied to the accurate quantification of Ara h1 in six milk-related beverages, two biscuits, and two candy bars with complicated matrices and presented a low-concentration quantitation capability. This method gives a new type of mass spectrometric immunoassay for rapid and ultrasensitive allergen regulation in the food industry and for individual allergen differentiation research.

Novel protein ligase based on dual split intein.

Inteins are unique single-turnover enzymes that can excise themselves from the precursor protein without the aid of any external cofactors or energy. In most cases, inteins are covalently linked with the extein sequences and protein splicing happens spontaneously. In this study, a novel protein ligation system was developed based on two atypical split inteins without cross reaction, in which the large segments of one S1 and one S11 split intein fusion protein acted as a protein ligase, the small segments (only several amino acids long) was fused to the N-extein and C-extein, respectively. The splicing activity was demonstrated in E. coli and in vitro with different extein sequences, which showed ∼15% splicing efficiency in vitro. The protein trans-splicing in vitro was further optimized, and possible reaction explanations were explored. As a proof of concept, we expect this approach to expand the scope of trans-splicing-based protein engineering and provide new clues for intein based protein ligase.

Arginine-linked HPV-associated E7 displaying bacteria-derived outer membrane vesicles as a potent antigen-specific cancer vaccine.

BACKGROUND: Bacteria-based cancer therapy have demonstrated innovative strategies to combat tumors. Recent studies have focused on gram-negative bacterial outer membrane vesicles (OMVs) as a novel cancer immunotherapy strategy due to its intrinsic properties as a versatile carrier. METHOD: Here, we developed an Human Papillomavirus (HPV)-associated E7 antigen displaying Salmonella-derived OMV vaccine, utilizing a Poly(L-arginine) cell penetrating peptide (CPP) to enhance HPV16 E7 (aa49-67) H-2 Db and OMV affinity, termed SOMV-9RE7. RESULTS: Due to OMV's intrinsic immunogenic properties, SOMV-9RE7 effectively activates adaptive immunity through antigen-presenting cell uptake and antigen cross-presentation. Vaccination of engineered OMVs shows immediate tumor suppression and recruitment of infiltrating tumor-reactive immune cells. CONCLUSION: The simplicity of the arginine coating strategy boasts the versatility of immuno-stimulating OMVs that can be broadly implemented to personalized bacterial immunotherapeutic applications.

Conditional protein splicing triggered by SUMO protease.

Conditional protein splicing is a powerful biotechnological tool that can be used to post-translationally control the activity of target proteins. Here we demonstrated a novel conditional protein splicing approach in which the small ubiquitin-like modifier (SUMO) protease induced the splicing of an atypical split intein. The engineered Ter DnaE-3 S11 split intein which has a small C-intein segment with only 6 amino acids was used in this study. A SUMO tag was fused to the N-terminus of the C-intein to inhibit the protein trans-splicing in vitro. The splicing products could be detected in 15 min with the addition of SUMO protease by western blotting and the splicing efficiency was ∼4-fold higher than the control without SUMO protease for overnight reaction. This engineered Ter DnaE-3 S11 split intein-mediated protein trans-splicing had been further shown to be triggered by SUMO protease in different exteins in vitro. Our study provides new insights into the regulation of protein splicing and is a promising tool for the control of protein structure and function in vitro.

Improved Electrical Output Performance of Cellulose-Based Triboelectric Nanogenerators Enabled by Negative Triboelectric Materials.

Cellulose-based triboelectric nanogenerators (TENGs) have attracted widespread attention due to the low cost and environmentally friendly characteristics of cellulose. However, achieving high electrical energy output from these generators still presents significant challenges. Here, cellulose is dissolved-regenerated to form a composite aerogel with high specific surface area, in which cellulose-based composites with excellent negative triboelectric properties are developed by coupling the rich 3D network structure of the regenerated cellulose aerogel, modified barium titanate, and poly(vinylidene fluoride). The TENGs assembled from the composite materials exhibit an output voltage of 1040 V and a current of 1.165 mA at an external force of 8 N and a frequency of 4 Hz, outperforming all cellulose-based negative triboelectric materials. In addition, the nanogenerators have a stable electrical energy output capacity, with no significant property degradation in 100 000 contact-separation tests. The excellent electrical output property of the composite materials enables them to harvest energy from human movement and waterdrops, demonstrating their great application prospects in wearable devices, energy harvesting devices, self-powered sensors, and other fields.

Localization of Salmonella and albumin-IL-2 to the tumor microenvironment augments anticancer T cell immunity.

BACKGROUND: For centuries, microbial-based agents have been investigated as a therapeutic modality for the treatment of cancer. In theory, these methods would be cheap to produce, broadly applicable in a wide array of cancer types, and could synergize with other cancer treatment strategies. We aimed to assess the efficacy of combining microbial-based therapy using Salmonella SL7207 with interleukin-2 (IL-2), a potent immunostimulatory agent, in the treatment of murine colon carcinoma. METHODS: Female BALB/c mice were implanted subcutaneously with CT26 tumors, a model of colon carcinoma. Mice bearing tumors were selected and administered Albumin-IL-2 (Alb-IL2), a fusion protein, for further analysis of anticancer effect. RESULTS: We demonstrated that Salmonella SL7207, a genetically modified strain of Salmonella enterica serovar Typhimurium, preferentially accumulates in the tumor microenvironment, potentiating it to stimulate localized innate immunity. We delivered IL-2 as a fusion protein, Alb-IL2, which we demonstrate to have preferential accumulation properties, bringing it to the tumor and secondary lymphoid organs. Treatment of tumor-bearing mice with Salmonella + Alb-IL2 leads to superior tumor control and enhanced overall survival compared to controls. When assessing immunological factors contributing to our observed tumor control, significantly enhanced T cell population with superior effector function was observed in mice treated with Salmonella + Alb-IL2. We confirmed that these T cells were indispensable to the observed tumor control through antibody-mediated T cell depletion experiments. CONCLUSIONS: These findings highlight the ability of Salmonella + Alb-IL2 to serve as a novel therapeutic approach to induce T cell-mediated antitumor immunity and exert long-term tumor control in a murine model of cancer.

Preparation and Characterization of Nanofibrous Membranes Electro-Spun from Blended Poly(l-lactide-co-ε-caprolactone) and Recombinant Spider Silk Protein as Potential Skin Regeneration Scaffold.

Biomaterial scaffolding serves as an important strategy in skin tissue engineering. In this research, recombinant spider silk protein (RSSP) and poly(L-lactide-co-ε-caprolactone) (PLCL) were blended in different ratios to fabricate nanofibrous membranes as potential skin regeneration scaffolds with an electro-spinning process. Scanning electron microscopy (SEM), water contact angles measurement, Fourier transform infrared (FTIR) spectroscopy, wide angle X-ray diffraction (WAXD), tensile mechanical tests and thermo-gravimetric analysis (TGA) were carried out to characterize the nanofibrous membranes. The results showed that the blending of RSSP greatly decreased the nanofibers' average diameter, enhanced the hydrophilicity, changed the microstructure and thermal properties, and could enable tailored mechanical properties of the nanofibrous membranes. Among the blended membranes, the PLCL/RSSP (75/25) membrane was chosen for further investigation on biocompatibility. The results of hemolysis assays and for proliferation of human foreskin fibroblast cells (hFFCs) confirmed the membranes potential use as skin-regeneration scaffolds. Subsequent culture of mouse embryonic fibroblast cells (NIH-3T3) demonstrated the feasibility of the blended membranes as a human epidermal growth factor (hEGF) delivery matrix. The PLCL/RSSP (75/25) membrane possessed good properties comparable to those of human skin with high biocompatibility and the ability of hEGF delivery. Further studies can be carried out on such membranes with chemical or genetic modifications to make better scaffolds for skin regeneration.

MRI features and differential diagnoses of congenital vaginal atresia.

Objective: To investigate the MRI manifestations of congenital vaginal atresia, analyze its imaging features, and improve the understanding of the disease. Methods: MRI findings and clinical data of 12 patients with congenital vaginal atresia confirmed by hysteroscopy and laparoscopic surgery were retrospectively analyzed. Vaginal atresia was classified according to vaginal dysplasia in AFS female genital malformation classification system. Results: In this study, 12 cases of congenital vaginal atresia were diagnosed by combined preoperative MRI with operative diagnosis. Among them, 10 patients all had type-I congenital vaginal atresia, and their uterus and cervix were normal (1 patient had ectopic renal malformation combined with left ovarian endometriosis cyst and 1 patient with uterine empyema). The other two cases were diagnosed congenital vaginal atresia type II (1 case merged with residual uterus, 1 case with cervical dysplasia). MRI mainly manifested as dilatation and hemorrhage in the uterine cavity, cervical canal and vaginal upper segment. T1WI showed high signal, T2WI showed slightly lower and slightly higher signal. The dilated vagina was above the perineal level. Conclusion: MRI features of congenital vaginal atresia have certain characteristics. MRI cannot only accurately assess the type of vaginal dysplasia and its associated complications, but also make objective evaluation and diagnosis, so it can be used as the best effective preoperative image evaluation.

The new antihypertensive drug iptakalim activates ATP-sensitive potassium channels in the endothelium of resistance blood vessels.

AIM: To investigate the mechanisms underlying the activation of ATP-sensitive potassium channels (K(ATP)) by iptakalim in cultured rat mesenteric microvascular endothelial cells (MVECs). METHODS: Whole-cell KATP currents were recorded in MVECs using automated patch clamp devices. Nucleotides (ATP, ADP and UDP) were added to the internal perfusion system, whereas other drugs were added to the cell suspension on NPC-1 borosilicate glass chips. RESULTS: Application of iptakalim (10 and 100 µmol/L) significantly increased the whole-cell K(ATP) currents, which were prevented by the specific K(ATP) blocker glibenclamide (1.0 µmol/L). The opening of K(ATP) channels by iptakalim depended upon the intracellular concentrations of ATP or NDPs: iptakalim activated K(ATP) channels when the intracellular ATP or NDPs were at 100 or 1000 µmol/L, and was ineffective when the non-hydrolysable ATP analogue ATPγS (1000 µmol/L) was infused into the cells. In contrast, the K(ATP) opener pinacidil activated K(ATP) channels when the intracellular concentrations of ATP or NDPs ranged from 10 to 5000 µmol/L, and even ATPγS (1000 µmol/L) was infused into the cells. CONCLUSION: Iptakalim activates K(ATP) channels in the endothelial cells of resistance blood vessels with a low metabolic status, and this activation is dependent on both ATP hydrolysis and ATP ligands.

Comparison of complications of the suprameatal approach and mastoidectomy with posterior tympanotomy approach in cochlear implantation: a meta-analysis.

BACKGROUND: Cochlear implantation (CI) is a popular procedure to preserve hearing in patients with severe-to-profound hearing loss. Evidence shows that the suprameatal approach (SMA) may help reducing the risk of the incidence of complications and shortening the surgery time, but there is still dispute. OBJECTIVES: The aim of this study was to compare the incidence of complications of SMA and the mastoidectomy with posterior tympanotomy approach (MPTA), and to find whether SMA yields better outcomes than MPTA. METHODS: We searched PubMed, the Cochrane Library, the Web of Science and Chinese Biomedical Literature databases, Chinese National Knowledge Infrastructure, the Chinese Science and Technology Journal Full-Text database, and Wangfang database. The latest data was accessed in March 2013. Review Manager 5.1 software was used for comprehensive quantification data analysis. RESULTS: Three studies were included in the meta-analysis, composed of 799 participants and reporting major and minor complications. The meta-analysis indicated no statistically significant difference in major and minor complications between the two approaches, except for facial nerve and chorda tympani injuries (OR = 0.13; 95% CI: 0.02, 0.67; p = 0.02; I(2) = 0%). CONCLUSIONS: Current evidence suggests that SMA may be clearly a good alternative to the classical surgery technique for CI in terms of reducing the incidence of facial nerve injury and chorda tympani sacrifice.

A rare transcript homozygous variants in CLRN1(USH3A) causes Usher syndrome type 3 in a Chinese family.

BACKGROUND: Usher syndrome type 3 (USH3) is an autosomal recessive inherited disorder caused by pathogenic variants in the CLRN1 gene. OBJECT: To evaluate the genotype-phenotype correlation of Usher syndrome type 3 (USH3) in a deaf-blind Chinese family of 3 generations with 2 patients. METHODS: We collected blood samples and clinical data from all of the pedigree family members. Genomic DNA was isolated from peripheral leukocytes using standard method. Targeted next generation sequencing and Sanger sequencing were performed to find the pathogenic variants in this family. Digital PCR and plasmid overexpression assay were used to verify the pathogenicity of variant sites in different transcripts. RESULTS: All patients developed bilateral sensorineural hearing loss (SHL), progressive vision loss and nyctalopia. NGS of genes for Usher syndrome, deafness and retinal dystrophy identified a locus mutation in CLRN1 that caused completely different amino acid changes in different transcripts[CLRN1:c.474T > A(P.Cys158Ter) at NM_001256819.2 or c.302T > A(p.Val101Asp) at NM_174878.3], and plasmid overexpression experiments confirmed that the c.474T > A(P.Cys158Ter, NM_001256819.2) was a pathogenic variant which has never been associated with Usher syndrome in China, and the transcript of this mutation was not the version commonly found worldwide. CONCLUSIONS: The CLRN1c.474T > A(NM_001256819.2) mutation is the causative variant in the Chinese family with USH3. The pathogenicity of different transcripts should be particularly considered in pathogenicity analysis.

Reconstructing Signaling Networks Using Biosensor Barcoding.

Understanding how signaling networks are regulated offers valuable insights into how cells and organisms react to internal and external stimuli and is crucial for developing novel strategies to treat diseases. To achieve this, it is necessary to delineate the intricate interactions between the nodes in the network, which can be accomplished by measuring the activities of individual nodes under perturbation conditions. To facilitate this, we have recently developed a biosensor barcoding technique that enables massively multiplexed tracking of numerous signaling activities in live cells using genetically encoded fluorescent biosensors. In this chapter, we detail how we employed this method to reconstruct the EGFR signaling network by systematically monitoring the activities of individual nodes under perturbations.

A novel intronic variant causing aberrant splicing identified in two deaf Chinese siblings with enlarged vestibular aqueducts.

OBJECTIVE: We aimed to evaluate the genotype-phenotype relationship in two Chinese family members with enlarged vestibular aqueduct (EVA). METHODS: We collected blood samples and clinical data from each pedigree family member. Genomic DNA was isolated from peripheral leukocytes using standard methods. Targeted next-generation sequencing and Sanger sequencing were performed to find the pathogenic mutation in this family. Minigene assays were used to verify whether the novel intronic mutation SLC26A4c.765+4A>G influenced mRNA splicing. RESULTS: Hearing loss in the patients with EVA was diagnosed using auditory tests and imaging examinations. Two pathogenic mutations, c.765+4A>G and c.919-2A>G were detected in SLC26A4. In vitro minigene analysis confirmed that c.765+4A>G variant could cause aberrant splicing, resulting in skipping over exon 6. CONCLUSIONS: The SLC26A4c.765+4A>G mutation is the causative variant in the Chinese family with EVA. Particular attention should be paid to intronic variants.

Calibration of FRET-based biosensors using multiplexed biosensor barcoding.

Förster resonance energy transfer (FRET) between fluorescent proteins (FPs) is widely used in the design of genetically encoded fluorescent biosensors, which are powerful tools for monitoring the dynamics of biochemical activities in live cells. FRET ratio, defined as the ratio between acceptor and donor signals, is often used as a proxy for the actual FRET efficiency, which must be corrected for signal crosstalk using donor-only and acceptor-only samples. However, the FRET ratio is highly sensitive to imaging conditions, making direct comparisons across different experiments and over time challenging. Inspired by a method for multiplexed biosensor imaging using barcoded cells, we reasoned that calibration standards with fixed FRET efficiency can be introduced into a subset of cells for normalization of biosensor signals. Our theoretical analysis indicated that the FRET ratio of high-FRET species relative to non-FRET species slightly decreases at high excitation intensity, suggesting the need for calibration using both high and low FRET standards. To test these predictions, we created FRET donor-acceptor pairs locked in "FRET-ON" and "FRET-OFF" conformations and introduced them into a subset of barcoded cells. Our results confirmed the theoretical predictions and showed that the calibrated FRET ratio is independent of imaging settings. We also provided a strategy for calculating the FRET efficiency. Together, our study presents a simple strategy for calibrated and highly multiplexed imaging of FRET biosensors, facilitating reliable comparisons across experiments and supporting long-term imaging applications.

Efficient mitigation of lithium dendrite by two-dimensional A-type molecular sieve membrane for lithium metal battery.

Uneven lithium deposition poses a primary challenge for lithium-ion batteries, as it often triggers the growth of lithium dendrites, thereby significantly compromising battery performance and potentially giving rise to safety concerns. Therefore, the high level of safety must be guaranteed to achieve the large-scale application of battery energy storage systems. Here, we present a novel separator design achieved by incorporating a two-dimensional A-type molecular sieve coating onto the polypropylene separator surface, which functions as an effective lithium ion redistribution layer. The results demonstrated that even after undergoing 1000 cycles, the cell equipped with a two-dimensional A-type molecular sieve-Polypropylene (2D-A-PP) separator still maintains an impressive capacity retention rate of 70 %. In contrast, cells equipped with Polypropylene (PP) separators exhibit capacity retention rates below 50 % after only 500 cycles. Additionally, the incorporation of a two-dimensional molecular sieve enhances the mechanical properties of the PP separator, thereby bolstering battery safety. This study proposes a novel concept for the design of lithium-ion battery separator materials, offering a fresh perspective on the development of separators with exceptional thermal stability, enhanced porosity, superior electrolyte affinity, and effective inhibition of lithium dendrite formation.

Salmonella immunotherapy engineered with highly efficient tumor antigen coating establishes antigen-specific CD8+ T cell immunity and increases in antitumor efficacy with type I interferon combination therapy.

Bacteria-based cancer therapy employs various strategies to combat tumors, one of which is delivering tumor-associated antigen (TAA) to generate specific immunity. Here, we utilized a poly-arginine extended HPV E7 antigen (9RE7) for attachment on Salmonella SL7207 outer membrane to synthesize the bacterial vaccine Salmonella-9RE7 (Sal-9RE7), which yielded a significant improvement in the amount of antigen presentation compared to the previous lysine-extended antigen coating strategy. In TC-1 tumor mouse models, Sal-9RE7 monotherapy decreased tumor growth by inducing E7 antigen-specific immunity. In addition, pairing Sal-9RE7 with adjuvant Albumin-IFNß (Alb-IFNß), a protein cytokine fusion, the combination significantly increased the antitumor efficacy and enhanced immunogenicity in the tumor microenvironment (TME). Our study made a significant contribution to personalized bacterial immunotherapy via TAA delivery and demonstrated the advantage of combination therapy.

Application progress of nanocellulose in food packaging: A review.

With the increasing environmental and ecological problems caused by petroleum-based packaging materials, the focus has gradually shifted to natural resources for the preparation of functional food packaging materials. In addition to biodegradable properties, nanocellulose (NC) mechanical properties, and rich surface chemistry are also fascinating and desired to be one of the most probable green packaging materials. In this review, we firstly introduce the recent progress of novel applications of NC in food packaging, including intelligent packaging, nano(bio)sensors, and nano-paper; secondly, we focus on the modification techniques of NC to summarize the properties (antimicrobial, mechanical, hydrophobic, antioxidant, and so on) that are required for food packaging, to expand the new synthetic methods and application areas. After presenting all the latest advances related to material design and sustainable applications, an overview summarizing the safety of NC is presented to promote a continuous and healthy movement of NC toward the field of truly sustainable packaging.

STAT1-Deficient HPV E6/E7-Associated Cancers Maintain Host Immunocompetency against Therapeutic Intervention.

Human papillomavirus (HPV) remains a global health concern because it contributes to the initiation of various HPV-associated cancers such as anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancer. In HPV-associated cancers, oncogenesis begins with an HPV infection, which is linked to the activation of the Janus protein tyrosine kinase (JAK)/STAT signaling pathway. Various STAT signaling pathways, such as STAT3 activation, have been well documented for their tumorigenic role, yet the role of STAT1 in tumor formation remains unclear. In the current study, STAT1-/- mice were used to investigate the role of STAT1 in the tumorigenesis of a spontaneous HPV E6/E7-expressing oral tumor model. Subsequently, our candidate HPV DNA vaccine CRT/E7 was administered to determine whether the STAT1-/- host preserves a therapeutic-responsive tumor microenvironment. The results indicated that STAT1-/- induces robust tumorigenesis, yet a controlled tumor response was attained upon CRT/E7 vaccination. Characterizing this treatment effect, immunological analysis found a higher percentage of circulating CD4+ and CD8+ T cells and tumor-specific cytotoxic T cells. In addition, a reduction in exhaustive lymphocyte activity was observed. Further analysis of a whole-cell tumor challenge affirmed these findings, as spontaneous tumor growth was more rapid in STAT1-/- mice. In conclusion, STAT1 deletion accelerates tumorigenesis, but STAT1-/- mice maintains immunocompetency in CRT/E7 treatments.

Physical Properties of the Second Type of Aciniform Spidroin (AcSp2) from Neoscona theisi Reveal a pH-Dependent Self-Assembly Repetitive Domain.

Orb-weaving spiders can use an array of specialized silks with diverse mechanical properties and functions for daily survival. Of all spider silk types, aciniform silk is the toughest silk fiber that combines high strength and elasticity. Although aciniform spidroins (AcSp) are the main protein in aciniform silks, their complete genes have rarely been characterized until now. Moreover, the structural and physical properties of AcSp variant proteins within the species are also unclear. Here, we present three full-length AcSp genes (named AcSp1A, AcSp1B, and AcSp2) from the orb-weaving spider Neoscona theisi and investigate the structural and mechanical features of these three AcSp repetitive domains. We demonstrate that all three AcSp proteins have mainly α-helical structural features in neutral solution and high thermal stability. Significantly, the AcSp2 repetitive domain shows a pH-dependent structural transition from α to ß conformations and can self-assemble into amyloid fibrils under acidic conditions, which is the first reported AcSp repetitive domain with pH-dependent self-assembly capacity. Compared with the other two AcSp spidroins, AcSp2 demonstrated the lowest expression level in the aciniform gland but had the highest strength for its silk fiber. Collectively, our findings provide new insight into the physical properties of each component of aciniform silk and expand the repertoire of known spidroin sequences for the synthesis of artificial silk materials.