Highly oriented BN-based TIMs with high through-plane thermal conductivity and low compression modulus.

In the pursuit of effective thermal management for electronic devices, it is crucial to develop insulation thermal interface materials (TIMs) that exhibit exceptional through-plane thermal conductivity, low thermal resistance, and minimal compression modulus. Boron nitride (BN), given its outstanding thermal conduction and insulation properties, has garnered significant attention as a potential material for this purpose. However, previously reported BN-based composites have consistently demonstrated through-plane thermal conductivity below 10 W m-1 K-1 and high compression modulus, whilst also presenting challenges in terms of mass production. In this study, low molecular weight polydimethylsiloxane (PDMS) and large-size BN were utilized as the foundational materials. Utilizing a rolling-curing integrated apparatus, we successfully accomplished the continuous preparation of large-sized, high-adhesion BN films. Subsequent implementation of stacking, cold pressing, and vertical cutting techniques enabled the attainment of a remarkable BN-based TIM, characterized by an unprecedented through-plane thermal conductivity of up to 12.11 W m-1 K-1, remarkably low compression modulus (55 kPa), and total effective thermal resistance (0.16 °C in2 W-1, 50 Psi). During the TIMs performance evaluation, our TIMs demonstrated superior heat dissipation capabilities compared with commercial TIMs. At a heating power density of 40 W cm-2, the steady-state temperature of the ceramic heating element was found to be 7 °C lower than that of the commercial TIMs. This pioneering feat not only contributes valuable technical insights for the development of high-performance insulating TIMs but also establishes a solid foundation for widespread implementation in thermal management applications across a range of electronic devices.

New therapeutic target NCF1-directed multi-bioactive conjugate therapies prevent preterm birth and adverse pregnancy outcomes.

Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality worldwide, yet the cellular and molecular mechanisms driving this condition remain undeciphered, thus limiting discovery of new therapies. In-depth analyses of human and mouse tissues associated with PTB, in combination with cellular studies, indicated that aberrantly high-expressed neutrophil cytoplasmic factor (NCF) 1 leads to oxidative distress, recruitment, and pro-inflammatory activation of neutrophils and macrophages, while sequentially overexpressed pro-inflammatory mediators induce contractions of uterine smooth muscle cells (USMCs) as well as apoptosis of USMCs and amniotic epithelial cells, thereby causing PTB. According to these new findings, we rationally engineered an amphiphilic macromolecular conjugate LPA by covalently integrating low-molecular-weight heparin, a reactive oxygen species-responsive/scavenging component, and an anti-inflammatory peptide. This bioengineered macromolecular conjugate can self-assemble into multi-bioactive nanoparticles (LPA NP). In a mouse model of PTB, LPA NP effectively delayed PTB and inhibited adverse pregnancy outcomes, by regulating NCF1-mediated oxidative-inflammatory cascades, i.e., attenuating oxidative stress, inhibiting inflammatory cell activation, reducing local inflammation, and decreasing contraction/apoptosis of myometrial cells. Packaging LPA NP into temperature-responsive, self-healing, and bioadhesive hydrogel further potentiated its in vivo efficacies after intravaginal delivery, by prolonging retention time, sustaining nanotherapy release, and increasing bioavailability in the placenta/uterus. Importantly, both the conjugate/nanotherapy and hydrogel formulations exhibited excellent safety profiles in pregnant mice, with negligible side effects on the mother and offspring.

An Osteoimmunomodulatory Biopatch Potentiates Stem Cell Therapies for Bone Regeneration by Simultaneously Regulating IL-17/Ferroptosis Signaling Pathways.

Currently, there are still great challenges in promoting bone defect healing, a common health problem affecting millions of people. Herein an osteoimmunity-regulating biopatch capable of promoting stem cell-based therapies for bone regeneration is developed. A totally biodegradable conjugate is first synthesized, which can self-assemble into bioactive nano micelles (PPT NMs). This nanotherapy effectively improves the osteogenesis of periodontal ligament stem cells (PDLSCs) under pathological conditions, by simultaneously regulating IL-17 signaling and ferroptosis pathways. Incorporation of PPT NMs into biodegradable electrospun nanofibers affords a bioactive patch, which notably improves bone formation in two rat bone defect models. A Janus bio patch is then engineered by integrating the bioactive patch with a stem cell sheet of PDLSCs. The obtained biopatch shows additionally potentiated bone regeneration capacity, by synergistically regulating osteoimmune microenvironment and facilitating stem cell differentiation. Further surface functionalization of the biopatch with tannic acid considerably increases its adhesion to the bone defect, prolongs local retention, and sustains bioactivities, thereby offering much better repair effects in rats with mandibular or cranial bone defects. Moreover, the engineered bioactive patches display good safety. Besides bone defects, this osteoimmunity-regulating biopatch strategy can be applied to promote stem cell therapies for spinal cord injury, wound healing, and skin burns.

Multichiral Mesoporous Silica Screws with Chiral Differential Mucus Penetration and Mucosal Adhesion for Oral Drug Delivery.

In the harsh gastrointestinal tract, helical bacteria with hierarchical chiral architectures possess strong abilities. Taking inspirations from nature, we developed a multichiral mesoporous silica nanoscrew (L/D-MCNS) as an efficient oral drug delivery platform by modifying the structural chiral silica nanoscrew (CNS) with L/D-alanine (L/D-Ala) enantiomers via the sequential application of a chiral template and postmodification strategies. We demonstrated that L-MCNS showed differential biological behaviors and superior advantages in oral adsorption compared to those of CNS, D-MCNS, and DL-MCNS. During the delivery, helical L/D-MCNS presenting distinctive topological structures, including small section area, large rough external surface, and a screw-like body, displayed multiple superiorities in mucus diffusion and mucosal adhesion. Meanwhile, the grafted chiral enantiomers enabled positive or negative chiral recognition with the biosystems. Once racemic flurbiprofen (FP) was encapsulated into the nanopores of L/D-MCNS (FP@L/D-MCNS), L/D-MCNS providing highly cross-linked and mesoscopic chiral nanochannels was beneficial for controlling the drug loading/release kinetics with chiral microenvironment sensitivity. Particularly, we noticed enantioselective absorption of FP in vivo, which could be attributed to the differential biological behaviors of L/D-MCNS. By simple design and regulation of the multilevel chirality of nanocarriers, L/D-MCNS can be employed for efficient oral drug delivery from the perspectives of material science, pharmacy, and bionics.

Immune Dysregulation in SARS-CoV-2 patients coinfected with Mycobacterium tuberculosis (Mtb) or HIV in China.

BACKGROUND: SARS-CoV-2 infections usually cause immune dysregulation in the human body. Studies of immunological changes resulting from coinfections with Mycobacterium tuberculosis (Mtb) or HIV are limited. METHODS: We conducted a retrospective study focusing on patients with COVID-19. A total of 550 patients infected with SARS-CoV-2 were enrolled in our study and categorized into four groups based on the presence of coinfections; 166 Delta-infected patients, among whom 103 patients had no coinfections, 52 who were coinfected with Mtb, 11 who were coinfected with HIV, and 384 Omicron-infected patients. By collecting data on epidemiologic information, laboratory findings, treatments, and clinical outcomes, we analyzed and compared clinical and immunological characteristics. RESULTS: Compared with those in the Delta group, the median white blood cell, CD4 + T-cell and B-cell counts were lower in the Mtb group and the HIV group. Except for those in the Omicron group, more than half of the patients in the three groups had abnormal chest CT findings. Among the three groups, there were no significant differences in any of the cytokines. Compared with those in the Delta group, the disease duration and LOS were longer in the Mtb group and the HIV group. For unvaccinated Delta-infected patients, in the Mtb and HIV groups, the number of B cells and CD4 + T cells was lower than that in the Delta group, with no significant difference in the LOS or disease duration. In the Mtb group, three (6%) patients presented with a disease duration greater than four months and had decreased lymphocyte and IL17A counts, possibly due to double infections in the lungs caused by SARS-CoV-2 and M. tuberculosis. CONCLUSIONS: We found that SARS-CoV-2 patients coinfected with Mtb or HIV exhibited a longer disease duration and longer LOS, with a decrease in B cells and CD4 + T cells, suggesting that these cells are related to immune function. Changes in cytokine levels suggest that coinfection with Mtb or HIV does not result in dysregulation of the immune response. Importantly, we discovered a chronic course of coinfection involving more than four months of Mtb and SARS-CoV-2 infection.

Pathogenesis-Guided Rational Engineering of Nanotherapies for the Targeted Treatment of Abdominal Aortic Aneurysm by Inhibiting Neutrophilic Inflammation.

Abdominal aortic aneurysm (AAA) remains a fatal disease in the elderly. Currently, no drugs can be clinically used for AAA therapy. Considering the pivotal role of neutrophils in the pathogenesis of AAA, herein we propose the targeted therapy of AAA by site-specifically regulating neutrophilic inflammation. Based on a luminol-conjugated α-cyclodextrin material (LaCD), intrinsically anti-inflammatory nanoparticles (NPs) were engineered by simple nanoprecipitation, which were examined as a nanotherapy (defined as LaCD NP). After efficient accumulation in the aneurysmal aorta and localization in pathologically relevant inflammatory cells in rats with CaCl2-induced AAA, LaCD NP significantly alleviated AAA progression, as implicated by the decreased aortic expansion, suppressed elastin degradation, inhibited calcification, and improved structural integrity of the abdominal aorta. By functionalizing LaCD NP with alendronate, a calcification-targeting moiety, the in vivo aneurysmal targeting capability of LaCD NP was considerably enhanced, thereby affording significantly potentiated therapeutic outcomes in AAA rats. Mechanistically, LaCD NP can effectively inhibit neutrophil-mediated inflammatory responses in the aneurysmal aorta. Particularly, LaCD NP potently attenuated the formation of neutrophil extracellular traps (NETs), thereby suppressing NETs-mediated pro-inflammatory events and NETosis-associated negative effects responsible for AAA progression. Consequently, we demonstrated the effectiveness and underlying mechanisms of anti-NETosis nanotherapies for the targeted treatment of AAA. Our findings provide promising insights into discovering precision therapies for AAA and other inflammatory vascular diseases.

RNA-binding protein RBM5 plays an essential role in acute myeloid leukemia by activating the oncogenic protein HOXA9.

BACKGROUND: The oncogenic protein HOXA9 plays a critical role in leukemia transformation and maintenance, and its aberrant expression is a hallmark of most aggressive acute leukemia. Although inhibiting the upstream regulators of HOXA9 has been proven as a significant therapeutic intervention, the comprehensive regulation network controlling HOXA9 expression in leukemia has not been systematically investigated. RESULTS: Here, we perform genome-wide CRISPR/Cas9 screening in the HOXA9-driven reporter acute leukemia cells. We identify a poorly characterized RNA-binding protein, RBM5, as the top candidate gene required to maintain leukemia cell fitness. RBM5 is highly overexpressed in acute myeloid leukemia (AML) patients compared to healthy individuals. RBM5 loss triggered by CRISPR knockout and shRNA knockdown significantly impairs leukemia maintenance in vitro and in vivo. Through domain CRISPR screening, we reveal that RBM5 functions through a noncanonical transcriptional regulation circuitry rather than RNA splicing, such an effect depending on DNA-binding domains. By integrative analysis and functional assays, we identify HOXA9 as the downstream target of RBM5. Ectopic expression of HOXA9 rescues impaired leukemia cell proliferation upon RBM5 loss. Importantly, acute protein degradation of RBM5 through auxin-inducible degron system immediately reduces HOXA9 transcription. CONCLUSIONS: We identify RBM5 as a new upstream regulator of HOXA9 and reveal its essential role in controlling the survival of AML. These functional and molecular mechanisms further support RBM5 as a promising therapeutic target for myeloid leukemia treatment.

Transient Compression Injury Triggers Neuroinflammation in a New Rat Model of Acute Peripheral Neuropathic Pain.

BACKGROUND: Peripheral neuropathic pain (NeP), induced by surgical intervention, is a well-known complication or sequela that remains a clinical challenge with few effective treatments. Ideal animal models that can recapitulate surgery-associated NeP remain to be established for both mechanistic studies and drug discovery. OBJECTIVES: We aimed to establish a new rat model of postsurgical NeP and describe its characteristics, as well as screen-promising therapeutic analgesics. STUDY DESIGN: Experimental research in rats. SETTING: The research took place in the laboratory of Xinqiao Hospital of the Third Military Medical University. METHODS: To mimic the surgical procedure associated with peripheral nerve injury (PNI), we established a transient compression injury (TCI) in the sciatic nerve. Behavioral tests of nociception were used to confirm the effect and the time course of this pain model. Histological assessments (transmission electron microscopy evaluation and immunohistochemistry) were performed to observe the neuropathological and immunological features. RNA sequencing (RNA-seq) of injured nerves and dorsal root ganglia (DRGs) was conducted to reveal the underlying mechanism in the newly established animal model and screen promising therapeutic targets. RESULTS: We established a rat model of TCI of the PN and detected nociceptive hypersensitivity of the injured (ipsilateral) nerve by behavioral tests. This animal model of NeP was further confirmed by observing time-dependent changes in mechanical allodynia and thermal hyperalgesia, as well as by examining the activation of microglia in the ipsilateral spinal dorsal horn. Pathophysiologically, TCI induced macroscopic nerve swelling and demyelination, which resulted in inflammatory responses in ipsilateral nerves. We also found inflammatory cell infiltration in the ipsilateral nerve that was sustained for several weeks, which further exacerbated local inflammation and oxidative stress. Moreover, RNA-seq revealed remarkably upregulated inflammatory reactions in PNs and the DRGs. Notably, the overexpression of inflammatory mediators and the infiltration of macrophages and microglia triggered remote immune responses in DRGs. Based on the RNA-seq results, we also confirmed that gabapentin (GBP) exerts therapeutic effects in TCI-induced NeP by regulating alpha2delta-1. LIMITATIONS: We did not compare the new rat model with the classical pain model (like chronic constriction injury or spared nerve injury) in histology or transcriptomics. CONCLUSIONS: We established a new rat model of NeP and thoroughly characterized neuroinflammation in the injured nerve and DRGs. Based on the upregulated genes in DRGs in this model, we screened a promising analgesic (GBP) capable of reducing pain hypersensitivity in surgery-associated NeP.

Prognostic significance of serum monoclonal proteins based on immunofixation electrophoresis in B-cell non-Hodgkin lymphoma.

The presence of serum monoclonal components has been associated with poor outcomes in various hematological malignancies. The current study focused on exploring its prognostic role in B-cell non-Hodgkin lymphoma. Our study represented 314 patients with information on serum immunofixation electrophoresis at diagnosis that were available with B-cell non-Hodgkin lymphoma. IFE was positive in 61 patients (19%). Baseline features were comparable between pairs of groups, poor ECOG PS, B symptoms, advanced stage, and high-risk IPI score were significantly more frequent in the + IFE group. Shorter PFS and OS of B-NHL patients were observed in patients who presented at diagnosis with a + IFE, and IFE was the independent predictor of PFS and OS in multivariate analysis. Moreover, integrating IFE into the IPI-M1, IPI-M2, and IPI-M3 models improved the area under the curve for more accurate survival prediction and prognosis. Serum monoclonal proteins are significant prognostic indicators for newly diagnosed B-cell non-Hodgkin lymphoma that can early identify patients with poor prognosis and guide clinical treatment decisions.

Simultaneous percutaneous microwave ablation and biopsy for highly suspected malignant pulmonary nodules: a retrospective cohort study.

Background: The conventional diagnosis and treatment for highly suspected malignant pulmonary nodules (PNs) can avoid unnecessary treatment to some extent. However, the relatively separate puncture processes may not only increase puncture-related complications, but also increase the patient's radiation exposure and hospitalization costs. The purpose of this study was to retrospectively analyze the effectiveness of simultaneous percutaneous microwave ablation (MWA) and percutaneous biopsy (PB) for PNs. Methods: From August 2015 to August 2022, 65 consecutive patients [48 solid nodules, 6 ground glass opacities (GGOs), 11 mixed nodules] with suspected single malignant PN underwent MWA and PB combination treatments at the First Affiliated Hospital of Zhengzhou University. The total of 30 patients in Group A underwent synchronous PB and MWA (strategy: low-power MWA-PB-high-power MWA), whereas 35 patients in Group B underwent asynchronous PB and MWA. The technical success, complete ablation (CA), complications, total procedure time (TPT), patient exposure dose (PED), hospitalization time, and costs were compared. An independent samples t-, χ2, or Fisher's exact tests were used. Results: The technical success (100% vs. 100%) and CA (100% vs. 97.1%) rates were not significantly different between Groups A and B. The complications of intrapulmonary hemorrhage (16.7% vs. 41.4%, P=0.02) and hemoptysis (0% vs. 8.6%, P=0.04) were significantly different between Groups A and B. TPT (41.6±7.9 vs. 57.3±8.8 min, P<0.001), PED (12.9±1.4 vs. 19.4±2.3 mSv, P<0.001), hospitalization stay (4.7±1.3 vs. 9.1±2.1 days, P<0.001) and costs (3,768.8±652.9 vs. 4,508.0±514.1 USD, P<0.001) also showed significant differences between Groups A and B. Conclusions: Synchronous PB and MWA for PNs is a safe and effective strategy that can decrease bleeding, PED, the hospitalization stay, and costs.

CAR-T cells targeting CD38 and LMP1 exhibit robust antitumour activity against NK/T cell lymphoma.

BACKGROUND: Natural killer/T cell lymphoma (NKTCL) is an aggressive lymphoma with a poor prognosis. Chimeric antigen receptor-transduced T (CAR-T) cell therapy has become a promising immunotherapeutic strategy against haematologic malignancies. METHODS: In this study, four CAR-T cell lines (CD38-CAR, LMP1-CAR, CD38-LMP1 tandem CAR 1 and CD38-LMP1 tandem CAR 2) were generated. The effect of CAR-T cells against NKTCL cells was evaluated both in vitro and in vivo. Expression of T cell activation markers and cytokines produced by CAR-T cells were detected by flow cytometry. RESULTS: The four CAR-T cell lines could effectively eliminate malignant NKTCL cells. They could be activated and produce inflammatory cytokines in a target-dependent manner. In vivo tests showed that the CAR-T cells exhibited significant antitumour effects in a xenotransplanted NKTCL mouse model. CONCLUSIONS: In summary, four CAR-T cell lines exhibited significant cytotoxicity against NKTCL cells both in vitro and in vivo. These results indicated the effective therapeutic promise of CD38 and LMP1 CAR-T cells in NKTCL.

Genome editing mRNA nanotherapies inhibit cervical cancer progression and regulate the immunosuppressive microenvironment for adoptive T-cell therapy.

CRISPR/Cas9-based genome editing is promising for therapy of cervical cancer by precisely targeting human papillomavirus (HPV). To develop CRISPR/Cas9-based genome editing nanotherapies, a pH-responsive hybrid nonviral nanovector was constructed for co-delivering Cas9 mRNA and guide RNAs (gRNAs) targeting E6 or E7 oncogenes. The pH-responsive nanovector was fabricated using an acetalated cyclic oligosaccharide (ACD), in combination with low molecular weight polyethyleneimine. Thus obtained hybrid ACD nanoparticles (defined as ACD NP) showed efficient loading for both Cas9 mRNA and E6 or E7 gRNA, giving rise to two pH-responsive genome editing nanotherapies E6/ACD NP and E7/ACD NP, respectively. Cellularly, ACD NP exhibited high transfection but low cytotoxicity in HeLa cervical carcinoma cells. Also, efficient genome editing of target genes was achieved in HeLa cells, with minimal off-target effects. In mice bearing HeLa xenografts, treatment with E6/ACD NP or E7/ACD NP afforded effective editing of target oncogenes and considerable antitumor activities. More importantly, treatment with E6/ACD NP or E7/ACD NP notably promoted CD8+ T cell survival by reversing the immunosuppressive microenvironment, thereby leading to synergistic antitumor effects by combination therapy using the gene editing nanotherapies and adoptive T-cell transfer. Consequently, our pH-responsive genome editing nanotherapies deserve further development for the treatment of HPV-associated cervical cancer, and they can also serve as promising nanotherapies to improve efficacies of other immune therapies against different advanced cancers by regulating the immunosuppressive tumor microenvironment.

PARP inhibitor exerts an anti-tumor effect via LMO2 and synergizes with cisplatin in natural killer/T cell lymphoma.

BACKGROUND: PARP inhibitor (PARPi), as a kind of DNA damage repair inhibitor, has been shown to be effective in various solid tumors and hematologic malignancies. Natural killer/T cell lymphoma (NKTCL) is a highly aggressive malignancy, the treatment of which has long been a major challenge in the clinic. Here, we investigated the efficacy and mechanism of PARPi, and the therapeutic value of PARPi combined with cisplatin in NKTCL. METHODS: The cell proliferation, cell apoptosis, and cell cycle of NKTCL cells were detected respectively by CCK-8 and flow cytometry. The changes of mRNA expression and protein level were measured respectively by mRNA-sequencing, quantitative real-time PCR, western blotting, and immunofluorescence. LMO2 expression was detected by immunohistochemistry and western blotting. Targeted knockdown of LMO2 was conducted by short hairpin RNA. The tumor xenograft models were established to evaluate the efficacy of drugs in vivo. RESULTS: PARPi inhibited cell proliferation, promoted cell apoptosis, and induced S-phase cell cycle arrest in NKTCL cells. PARPi led to the accumulation of DNA damage by blocking DNA repair and DNA replication. Additionally, LMO2 deficiency reduced the sensitivity of NKTCL cells to PARPi. Finally, the combination of PARPi and cisplatin exhibited significant synergistic effects both in vitro and in vivo. CONCLUSIONS: In summary, we found that PARPi exerted an anti-tumor effect via LMO2 and synergized with cisplatin in NKTCL, which provides the theoretical basis for the clinical application of PARPi.

Ubiquitin-proteasome system-based signature to predict the prognosis and drug sensitivity of hepatocellular carcinoma.

Background: Ubiquitin-proteasome system (UPS) is implicated in cancer occurrence and progression. Targeting UPS is emerging as a promising therapeutic target for cancer treatment. Nevertheless, the clinical significance of UPS in hepatocellular carcinoma (HCC) has not been entirely elucidated. Methods: Differentially expressed UPS genes (DEUPS) were screened from LIHC-TCGA datasets. The least absolute shrinkage and selection operator (LASSO) and stepwise multivariate regression analysis were conducted to establish a UPS-based prognostic risk model. The robustness of the risk model was further validated in HCCDB18, GSE14520, and GSE76427 cohorts. Subsequently, immune features, clinicopathologic characteristics, enrichment pathways, and anti-tumor drug sensitivity of the model were further evaluated. Moreover, a nomogram was established to improve the predictive ability of the risk model. Results: Seven UPS-based signatures (ATG10, FBXL7, IPP, MEX3A, SOCS2, TRIM54, and PSMD9) were developed for the prognostic risk model. Individuals with HCC with high-risk scores presented a more dismal prognosis than those with low-risk scores. Moreover, larger tumor size, advanced TNM stage, and tumor grade were observed in the high-risk group. Additionally, cell cycle, ubiquitin-mediated proteolysis, and DNA repair pathways were intimately linked to the risk score. In addition, obvious immune cell infiltration and sensitive drug response were identified in low-risk patients. Furthermore, both nomogram and risk score showed a significant prognosis-predictive ability. Conclusion: Overall, we established a novel UPS-based prognostic risk model in HCC. Our results will facilitate a deep understanding of the functional role of UPS-based signature in HCC and provide a reliable prediction of clinical outcomes and anti-tumor drug responses for patients with HCC.

Intrinsically bioactive and biomimetic nanoparticle-derived therapies alleviate asthma by regulating multiple pathological cells.

Asthma is a serious global public health concern. Airway neutrophilic inflammation is closely related to severe asthma, for which effective and safe therapies remain to be developed. Here we report nanotherapies capable of simultaneously regulating multiple target cells relevant to the pathogenesis of neutrophilic asthma. A nanotherapy LaCD NP based on a cyclic oligosaccharide-derived bioactive material was engineered. LaCD NP effectively accumulated in the injured lungs of asthmatic mice and mainly distributed in neutrophils, macrophages, and airway epithelial cells after intravenous or inhalation delivery, thereby ameliorating asthmatic symptoms and attenuating pulmonary neutrophilic inflammation as well as reducing airway hyperresponsiveness, remodeling, and mucus production. Surface engineering via neutrophil cell membrane further enhanced targeting and therapeutic effects of LaCD NP. Mechanistically, LaCD NP can inhibit the recruitment and activation of neutrophils, especially reducing the neutrophil extracellular traps formation and NLRP3 inflammasome activation in neutrophils. Also, LaCD NP can suppress macrophage-mediated pro-inflammatory responses and prevent airway epithelial cell death and smooth muscle cell proliferation, by mitigating neutrophilic inflammation and its direct effects on relevant cells. Importantly, LaCD NP showed good safety performance. Consequently, LaCD-derived multi-bioactive nanotherapies are promising for effective treatment of neutrophilic asthma and other neutrophil-associated diseases.

Development of a model by LASSO to predict hospital length of stay (LOS) in patients with the SARS-Cov-2 omicron variant.

The length of stay (LOS) in hospital varied considerably in different patients with COVID-19 caused by SARS-CoV-2 Omicron variant. The study aimed to explore the clinical characteristics of Omicron patients, identify prognostic factors, and develop a prognostic model to predict the LOS of Omicron patients. This was a single center retrospective study in a secondary medical institution in China. A total of 384 Omicron patients in China were enrolled. According to the analyzed data, we employed LASSO to select the primitive predictors. The predictive model was constructed by fitting a linear regression model using the predictors selected by LASSO. Bootstrap validation was used to test performance and eventually we obtained the actual model. Among these patients, 222 (57.8%) were female, the median age of patients was 18 years and 349 (90.9%) completed two doses of vaccination. Patients on admission diagnosed as mild were 363 (94.5%). Five variables were selected by LASSO and a linear model, and those with P < 0.05 were integrated into the analysis. It shows that if Omicron patients receive immunotherapy or heparin, the LOS increases by 36% or 16.1%. If Omicron patients developed rhinorrhea or occur familial cluster, the LOS increased by 10.4% or 12.3%, respectively. Moreover, if Omicron patients' APTT increased by one unit, the LOS increased by 0.38%. Five variables were identified, including immunotherapy, heparin, familial cluster, rhinorrhea, and APTT. A simple model was developed and evaluated to predict the LOS of Omicron patients. The formula is as follows: Predictive LOS = exp(1*2.66263 + 0.30778*Immunotherapy + 0.1158*Familiar cluster + 0.1496*Heparin + 0.0989*Rhinorrhea + 0.0036*APTT).

Rapid and persistent bactericidal cotton fabrics finished facilely with reactive N-halamine.

Cotton fabrics (CFs) with persistent and rapid bactericidal capability would be of great significance for daily health protection because CFs are very suitable for the growth and reproduction of microorganisms. Herein, we developed a reactive N-halamine compound, 3-(3-hydroxypropyl diisocyanate)-5,5-dimethylhydantoin (IPDMH), that can be covalently bound to a CF to generate a bactericidal CF after chlorination (CF-DMF-Cl) without damaging its surface morphology. The antibacterial rates of CF-DMF-Cl (0.5 wt% IPDMH) against the gram-negative bacterium Escherichia coli (E. coli) and gram-positive bacterium Staphylococcus aureus (S. aureus) reached 99.99 % and were maintained at 90 % (against E. coli) and 93.5 % (against S. aureus) after 50 laundering cycles. The combination of contact killing and release killing mechanisms by CF-PDM-Cl leads to its rapid and persistent bactericidal activity. In addition, CF-DMF-Cl exhibits adequate biocompatibility, well-maintained mechanical properties, air/water vapor permeability and whiteness. Therefore, the proposed CF-DMF-Cl has great potential applications as a bactericidal CF for use in medical textiles, sportswear, home dressings, and so on.

Pathologically triggered in situ aggregation of nanoparticles for inflammation-targeting amplification and therapeutic potentiation.

Uncontrolled and persistent inflammation is closely related to numerous acute and chronic diseases. However, effective targeting delivery systems remain to be developed for precision therapy of inflammatory diseases. Herein we report a novel strategy for engineering inflammation-accumulation nanoparticles via phenolic functionalization. Different phenol-functionalized nanoparticles were first developed, which can undergo in situ aggregation upon triggering by the inflammatory/oxidative microenvironment. Phenolic compound-decorated poly (lactide-co-glycolide) nanoparticles, in particular tyramine (Tyr)-coated nanoparticles, showed significantly enhanced accumulation at inflammatory sites in mouse models of colitis, acute liver injury, and acute lung injury, mainly resulting from in situ cross-linking and tissue anchoring of nanoparticles triggered by local myeloperoxidase and reactive oxygen species. By combining a cyclodextrin-derived bioactive material with Tyr decoration, a multifunctional nanotherapy (TTN) was further developed, which displayed enhanced cellular uptake, anti-inflammatory activities, and inflammatory tissue accumulation, thereby affording amplified therapeutic effects in mice with colitis or acute liver injury. Moreover, TTN can serve as a bioactive and inflammation-targeting nanoplatform for site-specifically delivering a therapeutic peptide to the inflamed colon post oral administration, leading to considerably potentiated in vivo efficacies. Preliminary studies also revealed good safety of orally delivered TTN. Consequently, Tyr-based functionalization is promising for inflammation targeting amplification and therapeutic potentiation of nanotherapies.