Biometric-Tuned E-Skin Sensor with Real Fingerprints Provides Insights on Tactile Perception: Rosa Parks Had Better Surface Vibrational Sensation than Richard Nixon.

The dense mechanoreceptors in human fingertips enable texture discrimination. Recent advances in flexible electronics have created tactile sensors that effectively replicate slowly adapting (SA) and rapidly adapting (RA) mechanoreceptors. However, the influence of dermatoglyphic structures on tactile signal transmission, such as the effect of fingerprint ridge filtering on friction-induced vibration frequencies, remains unexplored. A novel multi-layer flexible sensor with an artificially synthesized skin surface capable of replicating arbitrary fingerprints is developed. This sensor simultaneously detects pressure (SA response) and vibration (RA response), enabling texture recognition. Fingerprint ridge patterns from notable historical figures - Rosa Parks, Richard Nixon, Martin Luther King Jr., and Ronald Reagan - are fabricated on the sensor surface. Vibration frequency responses to assorted fabric textures are measured and compared between fingerprint replicas. Results demonstrate that fingerprint topography substantially impacts skin-surface vibrational transmission. Specifically, Parks' fingerprint structure conveyed higher frequencies more clearly than those of Nixon, King, or Reagan. This work suggests individual fingerprint ridge morphological variation influences tactile perception and can confer adaptive advantages for fine texture discrimination. The flexible bioinspired sensor provides new insights into human vibrotactile processing by modeling fingerprint-filtered mechanical signals at the finger-object interface.

Tunable Dual Self-Healing Composite Coatings with Self-Assembled Structures Regulated by Janus Nanoparticles.

The durability of concrete structures can be enhanced in a convenient and permanent manner through the surface protection of cementitious materials with composite polymer coatings. However, polymer coatings are susceptible to various mechanical and physical deterioration in complex and variable environments. In this paper, the theory of polymer microstructure regulation was employed to improve the sustainability of the protective performance of composite coatings. The self-assembled core-shell structure regulated by amphiphilic Janus nanoparticles is employed to modify the tunable polystyrene acrylate-polysiloxane self-healing coatings. The results demonstrate that the adhesion strength of the prepared self-assembled coating reached 3.7 MPa, which is sufficient to resist the damage to the microstructure of cementitious materials caused by physical erosion, seepage, and ionic corrosion. The self-healing coating, regulated by Janus particles, exhibited a residual creep of only 57.03% and a maximum loss angle tangent of 0.381. Furthermore, the material exhibited a superior shape memory function due to the presence of strong hydrogen bonding. The regulated self-healing coating repaired the polymer structural damage under mechanical and thermal deformation by bridging and filling effects. The coating demonstrated a tensile strength recovery of up to 71.23% in a wetted state, accompanied by a rapid restoration of its electrochemical properties and corrosion resistance. Furthermore, the self-healing emulsion penetrates the substrate defects and forms numerous polymer crystalline particles that effectively fill the microcracks.

On Demand Bioorthogonal Switching of an Antibody-Conjugated SPECT Probe to a Cytotoxic Payload: from Imaging to Therapy.

Antibody-drug conjugates (ADCs) for the treatment of cancer aim to achieve selective delivery of a cytotoxic payload to tumor cells while sparing normal tissue. In vivo, multiple tumor-dependent and -independent processes act on ADCs and their released payloads to impact tumor-versus-normal delivery, often resulting in a poor therapeutic window. An ADC with a labeled payload would make synchronous correlations between distribution and tissue-specific pharmacological effects possible, empowering preclinical and clinical efforts to improve tumor-selective delivery; however, few methods to label small molecules without destroying their pharmacological activity exist. Herein, we present a bioorthogonal switch approach that allows a radiolabel attached to an ADC payload to be removed tracelessly at will. We exemplify this approach with a potent DNA-damaging agent, the pyrrolobenzodiazepine (PBD) dimer, delivered as an antibody conjugate targeted to lung tumor cells. The radiometal chelating group, DOTA, was attached via a novel trans-cyclooctene (TCO)-caged self-immolative para-aminobenzyl (PAB) linker to the PBD, stably attenuating payload activity and allowing tracking of biodistribution in tumor-bearing mice via SPECT-CT imaging (live) or gamma counting (post-mortem). Following TCO-PAB-DOTA reaction with tetrazines optimized for extra- and intracellular reactivity, the label was removed to reveal the unmodified PBD dimer capable of inducing potent tumor cell killing in vitro and in mouse xenografts. The switchable antibody radio-drug conjugate (ArDC) we describe integrates, but decouples, the two functions of a theranostic given that it can serve as a diagnostic for payload delivery in the labeled state, but can be switched on demand to a therapeutic agent (an ADC).

Integrated bioinformatics combined with machine learning to analyze shared biomarkers and pathways in psoriasis and cervical squamous cell carcinoma.

Background: Psoriasis extends beyond its dermatological inflammatory manifestations, encompassing systemic inflammation. Existing studies have indicated a potential risk of cervical cancer among patients with psoriasis, suggesting a potential mechanism of co-morbidity. This study aims to explore the key genes, pathways, and immune cells that may link psoriasis and cervical squamous cell carcinoma (CESC). Methods: The cervical squamous cell carcinoma dataset (GSE63514) was downloaded from the Gene Expression Omnibus (GEO). Two psoriasis-related datasets (GSE13355 and GSE14905) were merged into one comprehensive dataset after removing batch effects. Differentially expressed genes were identified using Limma and co-expression network analysis (WGCNA), and machine learning random forest algorithm (RF) was used to screen the hub genes. We analyzed relevant gene enrichment pathways using GO and KEGG, and immune cell infiltration in psoriasis and CESC samples using CIBERSORT. The miRNA-mRNA and TFs-mRNA regulatory networks were then constructed using Cytoscape, and the biomarkers for psoriasis and CESC were determined. Potential drug targets were obtained from the cMAP database, and biomarker expression levels in hela and psoriatic cell models were quantified by RT-qPCR. Results: In this study, we identified 27 key genes associated with psoriasis and cervical squamous cell carcinoma. NCAPH, UHRF1, CDCA2, CENPN and MELK were identified as hub genes using the Random Forest machine learning algorithm. Chromosome mitotic region segregation, nucleotide binding and DNA methylation are the major enrichment pathways for common DEGs in the mitotic cell cycle. Then we analyzed immune cell infiltration in psoriasis and cervical squamous cell carcinoma samples using CIBERSORT. Meanwhile, we used the cMAP database to identify ten small molecule compounds that interact with the central gene as drug candidates for treatment. By analyzing miRNA-mRNA and TFs-mRNA regulatory networks, we identified three miRNAs and nine transcription factors closely associated with five key genes and validated their expression in external validation datasets and clinical samples. Finally, we examined the diagnostic effects with ROC curves, and performed experimental validation in hela and psoriatic cell models. Conclusions: We identified five biomarkers, NCAPH, UHRF1, CDCA2, CENPN, and MELK, which may play important roles in the common pathogenesis of psoriasis and cervical squamous cell carcinoma, furthermore predict potential therapeutic agents. These findings open up new perspectives for the diagnosis and treatment of psoriasis and squamous cell carcinoma of the cervix.

Deep Learning-Based Microscopic Cell Detection using Inverse Distance Transform and Auxiliary Counting.

Microscopic cell detection is a challenging task due to significant inter-cell occlusions in dense clusters and diverse cell morphologies. This paper introduces a novel framework designed to enhance automated cell detection. The proposed approach integrates a deep learning model that produces an inverse distance transform-based detection map from the given image, accompanied by a secondary network designed to regress a cell density map from the same input. The inverse distance transform-based map effectively highlights each cell instance in the densely populated areas, while the density map accurately estimates the total cell count in the image. Then, a custom counting-aided cell center extraction strategy leverages the cell count obtained by integrating over the density map to refine the detection process, significantly reducing false responses and thereby boosting overall accuracy. The proposed framework demonstrated superior performance with F-scores of 96.93%, 91.21%, and 92.00% on the VGG, MBM, and ADI datasets, respectively, surpassing existing state-of-the-art methods. It also achieved the lowest distance error, further validating the effectiveness of the proposed approach. These results demonstrate significant potential for automated cell analysis in biomedical applications.

The relativity analysis of hypoxia inducible factor-1α in pulmonary arterial hypertension (ascites syndrome) in broilers: a review.

Ascites syndrome (AS) in broiler chickens, also known as pulmonary arterial hypertension (PAH), is a significant disease in the poultry industry. It is a nutritional metabolic disease that is closely associated with hypoxia-inducible factors and rapid growth. The rise in pulmonary artery pressure is a crucial characteristic of AS and is instrumental in its development. Hypoxia-inducible factor 1α (HIF-1α) is an active subunit of a key transcription factor in the oxygen-sensing pathway. HIF-1α plays a vital role in oxygen homeostasis and the development of pulmonary hypertension. Studying the effects of HIF-1α on pulmonary hypertension in humans or mammals, as well as ascites in broilers, can help us understand the pathogenesis of AS. Therefore, this review aims to (1) summarize the mechanism of HIF-1α in the development of pulmonary hypertension, (2) provide theoretical significance in explaining the mechanism of HIF-1α in the development of pulmonary arterial hypertension (ascites syndrome) in broilers, and (3) establish the correlation between HIF-1α and pulmonary arterial hypertension (ascites syndrome) in broilers. HIGHLIGHTSExplains the hypoxic mechanism of HIF-1α.Linking HIF-1α to pulmonary hypertension in broilers.Explains the role of microRNAs in pulmonary arterial hypertension in broilers.

Whole-genome sequence of Porphyromonas pogonae PP01-1, a human strain harbouring blaOXA-347 and tet(Q)with chromosomal location.

OBJECTIVES: The aim of this study was to characterise the first complete genome of Porphyromonas pogonae strain PP01-1 of human origin in China. METHODS: The Illumina NovaSeq 6000 (200X coverage) and Nanopore MinION platforms (100× coverage) were used for genome sequencing. A de novo hybrid assembly of short Illumina reads and long MinION reads was performed using Unicycler (v.0.5.0). Genome annotation of PP01-1 was performed using the prokaryotic gene-prediction tool Prokka1.14.6. The genome was further analysed using several bioinformatics tools, including ResFinder, VFDB, VirulenceFinder, Type Strain Genome Server, AntiSMASH, PathogenFinder, MobileElementfinder, CRISPRFinder, and IslandViewer. RESULTS: The assembled circular genome of P. pogonae strain PP01-1 was 2 916 423 bp in length, with a GC content of 41.0%, and no plasmid sequence was detected. A total of 2399 coding sequences were predicted by Prokka. PP01-1 harbours antimicrobial resistance genes blaOXA-347 (ß-lactamase resistance), tet(Q) (tetracycline resistance), and floR (chloramphenicol and florfenicol resistance). CONCLUSIONS: Here, we are the first to report the complete genome of P. pogonae strain PP01-1 of human origin. In this strain, we first identified blaOXA-347 and tet(Q) in P. pogonae, which will pave the way for further analysis that could identify the potential mechanism of antibiotic resistance and virulence factors in P. pogonae.

Potent cancer therapy by liposome microstructure tailoring with active-to-passive targeting and shell-to-core thermosensitive features.

Liposomes have been widely studied as drug carriers for clinical application, and the key issue is how to achieve effective delivery through targeting strategies. Even though certain cell-level targeting or EPR effect designs have been developed, reaching sufficient drug concentration in intracellular regions remains a challenge due to the singularity of functionality. Herein, benefiting from the unique features of tumor from tissue to cell, a dual-thermosensitive and dual-targeting liposome (DTSL) was creatively fabricated through fine microstructure tailoring, which holds intelligent both tissue-regulated active-to-passive binding and membrane-derived homologous-fusion (HF) properties. At the micro level, DTSL can actively capture tumor cells and accompany the enhanced HF effect stimulated by self-constriction, which achieves a synergistic promotion effect targeting tissues to cells. As a result, this first active-then passive targeting process makes drug delivery more accurate and effective, and after dynamic targeting into cells, the nucleus of DTSL undergoes further thermally responsive contraction, fully releasing internal drugs. In vivo experiments showed that liposomes with dual targeting and dual thermosensitive features almost completely inhibited tumor growth. Summarized, these results provide a reference for a rational design and microstructural tailoring of the liposomal co-delivery system of drugs, suggesting that active-to-passive dual-targeting DTSL can function as a new strategy for cancer treatment.

[Different concentrations of adapalene induce differentiation and apoptosis of SH-SY5Y cells]. / 不同浓度阿达帕林诱导SH-SY5Y细胞的分化及凋亡.

OBJECTIVES: To investigate the effects of different concentrations of adapalene on the morphology and functions of neuroblastoma cell line SH-SY5Y, as well as its role in inducing cell differentiation and apoptosis. METHODS: SH-SY5Y cells were divided into control group, low concentration (0.1 µM and 1 µM) adapalene groups, and high concentration (10 µM) adapalene group. Time-lapse microscopy was used to observe the morphological changes of SH-SY5Y cells. Immunofluorescence staining was performed to detect the expression of neuronal specific marker ßIII-tubulin and mature neuronal marker neurofilament heavy polypeptide (NFH). Multi-electrode array was used to record the electrophysiological features of SH-SY5Y cells. Cell apoptosis was evaluated using a cell apoptosis detection kit. RESULTS: Low concentrations of adapalene promoted the formation of neurite outgrowth in SH-SY5Y cells, with the neurites interconnected to form a network. Spontaneous discharge activity was observed in SH-SY5Y cells treated with low concentrations of adapalene. Compared to the control group, the expression of ßIII-tubulin and NFH increased in the 1 µM adapalene group, while the level of cell apoptosis increased in the high concentration adapalene group (P<0.05). CONCLUSIONS: Low concentrations of adapalene can induce differentiation of SH-SY5Y cells into mature functional neurons, while high concentrations of adapalene can induce apoptosis in SH-SY5Y cells.

Camrelizumab, chemotherapy and apatinib in the neoadjuvant treatment of resectable oesophageal squamous cell carcinoma: a single-arm phase 2 trial.

Background: In resectable oesophageal squamous cell carcinoma (ESCC), the efficacy of camrelizumab combined with chemotherapy and apatinib followed by minimally invasive oesophagectomy is not clear. We aimed to fill this knowledge gap. Methods: This investigator-initiated, single-arm, prospective, phase 2 trial was performed at the Second Affiliated Hospital of Zhejiang University, China. Patients (aged 18-75 years) who were histologically or cytologically diagnosed with ESCC were deemed suitable to participate in this trial. Patients received 2-3 cycles of neoadjuvant therapy with camrelizumab, nedaplatin, albumin paclitaxel, and apatinib; each cycle was repeated every 14 days. Surgery occurred 4-6 weeks after the last neoadjuvant treatment cycle. The primary outcome was the pathological complete response (PCR) rate of the tumour and lymph nodes. The changes in the peripheral blood immunoprofile among patients without PCR (ie, non-PCR [NPCR]) and with PCR were assessed by mass cytometry. This study was registered with ClinicalTrials.gov, NCT04666090. Findings: 42 patients were enrolled between November 23, 2020 and December 31, 2022. The disease control rate was 100.0% (95% CI, 91.6-100%), and the objective response rate was 83.3% (95% CI, 68.6-93.0%). Six (14.3%) patients experienced grade 3 adverse events. The most common were white blood cell count decrease (31.0%), alopecia (81.0%), asthenia (38.1%), and reactive cutaneous capillary endothelial proliferation (35.7%). 41 patients received minimally invasive oesophagectomy; all 41patients achieved R0 resection, and 18 (43.9%, 95% CI, 28.5-60.3%) patients achieved PCR. The median follow-up was 23 months and the 2-year survival rate was 85.9%. T-cell subsets in both the PCR and NPCR groups exhibited consistency in response to neoadjuvant therapy. In contrast, some of natural killer (NK) cells (NK-C03, NK-C11), B cells (B-C06) and monocytes (M-C05), exhibited significant differences between the PCR and NPCR groups before neoadjuvant therapy. M-C06 had a significant difference in the PCR group and NPCR group after neoadjuvant therapy. NK-C12 and B-C15 showed significant differences both before and after neoadjuvant therapy. Interpretation: The application of camrelizumab, chemotherapy and apatinib in the neoadjuvant setting for locally advanced ESCC has shown promising antitumour activity and an acceptable safety profile in this single-arm study. In the neoadjuvant setting, NK cell, B cell, and monocyte subsets exhibited greater predictive power for immunotherapy responsiveness than T-cell subsets. Longer follow-up to assess survival outcomes and a phase 3 randomised trial are needed to further evaluate the proposed treatment. Funding: The China Anti-Cancer Association and the "Leading Goose" Research and Development Project of Zhejiang Province.

Surface Coordination Environment Engineering on PtxCu1-x Alloy Catalysts for the Efficient Photocatalytic Reduction of CO2 to CH4.

Alloy catalysts have been reported to be robust in catalyzing various heterogeneous reactions due to the synergistic effect between different metal atoms. In this work, aimed at understanding the effect of the coordination environment of surface atoms on the catalytic performance of alloy catalysts, a series of PtxCu1-x alloy model catalysts supported on anatase-phase TiO2 (PtxCu1-x/Ti, x = 0.4, 0.5, 0.6, 0.8) were developed and applied in the classic photocatalytic CO2 reduction reaction. According to the results of catalytic performance evaluation, it was found that the photocatalytic CO2 reduction activity on PtxCu1-x/Ti showed a volcanic change as a function of the Pt/Cu ratio, the highest CO2 conversion was achieved on Pt0.5Cu0.5/Ti, with CH4 as the main product. Further systematic characterizations and theoretical calculations revealed that the equimolar amounts of Pt and Cu in Pt0.5Cu0.5/Ti facilitated the generation of more Cu-Pt-paired sites (i.e., the higher coordination number of Pt-Cu), which would favor a bridge adsorption configuration of CO2 and facilitate the electron transfer, thus resulting in the highest photocatalytic CO2 reduction efficiency on Pt0.5Cu0.5/Ti. This work provided new insights into the design of excellent CO2 reduction photocatalysts with high CH4 selectivity from the perspective of surface coordination environment engineering on alloy catalysts.

Analysis of the effect of reconstructing the ossicular chain under otoendoscopy with and without a stapes superstructure.

BACKGROUND: Numerous studies have been conducted on the effect of the stapes superstructure after ossicular chain reconstruction, but the findings are not uniform. OBJECTIVE: To compare the hearing outcomes of ossicular chain reconstruction with partial ossicular replacement prosthesis (PORP) or total ossicular replacement prosthesis (TORP) under otoendoscopy. MATERIALS AND METHODS: The records of 111 patients diagnosed with chronic suppurative otitis media were retrospectively analyzed. These patients were divided into PORP group (n = 57) and TORP group (n = 54). They were further subdivided into subgroups PORP-a (with a malleus handle) and PORP-b (without a malleus handle), subgroups TORP-a and TORP-b. Pre- and postoperative audiometric results were analyzed. RESULTS: The mean postoperative air conduction hearing thresholds improvement, mean air-bone gap improvement, and the success rate of reconstruction were significantly higher in the PORP group than in the TORP group (p < .05). The mean postoperative air conduction hearing thresholds improvement and the success rate of reconstruction were significantly higher in the PORP-a group than in the TORP-a group (p < .05); and similar results were concluded in comparison of the PORP-b group and the TORP-b group. CONCLUSIONS AND SIGNIFICANCE: The stapes superstructure has an important positive effect on the postoperative outcome of endoscopic ossicular chain reconstruction.

Fe(II)-catalyzed phase transformation of Cd(II)-bearing ferrihydrite-kaolinite associations under anoxic conditions: New insights to role of kaolinite and fate of Cd(II).

Cadmium-bearing ferrihydrite-kaolinite associations (Cd-associations) are commonly found in cadmium-contaminated paddy soils in tropical and subtropical regions. In the presence of anaerobic conditions caused by flooding, the creation of Fe(II) can facilitate the transformation of ferrihydrite into secondary Fe (hydr)oxides, resulting in the redistribution of Cd. However, the role of kaolinite in iron oxides transformation and changes in Cd chemical species have largely not been determined. In this study, Cd-associations were prepared for reaction with Fe(II) under anoxic conditions. The results obtained from powder XRD and EXAFS indicated that the presence of kaolinite association noticeably hastened the transformation of ferrihydrite into crystalline goethite. Specific surface area and electrochemical analyses revealed that smaller particle sizes and higher reactivity of ferrihydrite within Cd-associations collaboratively contribute to the acceleration. Chemical analyses demonstrated a significant negative correlation between ferrihydrite-Fe and aqueous-Cd, and a significant positive correlation between crystalline-Fe and residual-Cd. HRTEM analyses indicated that a portion of the Cd was incorporated into the crystal lattices of lepidocrocite and goethite, with the majority of Cd being sequestered within goethite lattice. These findings provide new insights into the roles of clay minerals in the geochemical cycling of Fe and Cd in paddy soils under anoxic conditions.

Complete remission of gallbladder neuroendocrine carcinoma with liver metastasis by tislelizumab plus chemotherapy: a case report.

Background: Gallbladder neuroendocrine carcinoma (GB-NEC) is an extremely rare cancer with a poor prognosis in the clinic. Although surgical resection remains the primary and preferred therapeutics, many patients are in a late stage and lose the opportunity for surgery. However, due to the extremely low morbidity, the specific treatment guidelines for GB-NEC have not been established. Case presentation: A 52-year-old woman was admitted to our hospital with the chief complaint of "almost 1 month after palliative surgery for metastatic gallbladder carcinoma." According to the results of pathological findings and imaging manifestations, the patient was diagnosed with GB-NEC with a clinical stage of pT3N1M1 (IVB). The patient then received tislelizumab plus EP chemotherapy (etoposide 100 mg + cisplatin 30 mg, d1-3) every 3 weeks for 8 cycles from 12 November, 2021, followed by maintenance therapy (tislelizumab alone) every 3 weeks until now. The tumor response was evaluated as complete remission since 13 February, 2023. As of the last follow-up, the patient remains alive, with no complaints of discomfort. Conclusions: Gallbladder NEC has no specific symptoms, and the diagnosis is based on pathological and immunohistochemical results. The therapeutic course and efficacy of the case in this study indicates that the application of PD-1 inhibitor might be a feasible therapeutic option for GB-NEC. However, this potential strategy needs validation by further clinical studies in the future.

Design, Synthesis, and Antitumor Activity Evaluation of Artemisinin Bivalent Ligands.

Five artemisinin bivalent ligands molecules 4a-4e were designed, synthesized, and confirmed by 1H NMR, 13C NMR, and low-resolution mass spectrometry, and the bioactivities of the target compounds were investigated against four human tumor cell lines in vitro, including BGC-823, HepG-2, MCF-7, and HCT-116. The results showed 4a, 4d, and 4e exhibited significantly tumor cell inhibitory activity compared with the artemisinin and dihydroartemisinin; compound 4e has good biological activity inhibiting BGC-823 with an IC50 value of 8.30 µmol/L. Then, the good correlations with biological results were validated by molecular docking through the established bivalent ligands multi-target model, which showed that 4e could bind well with the antitumor protein MMP-9.

Comparative structural, digestion and absorption characterization of three common extruded plant proteins.

Extruded plant proteins, also known as textured vegetable proteins (TVPs), serve as vital components in plant-based meat analogue, yet their structural and nutritional characteristics remain elusive. In this study, we examined the impact of high-moisture (HM) and low-moisture (LM) extrusion on the structures, digestion and absorption of three types of plant proteins. Extrusion transformed plant proteins from spherical to fibrous forms, and formed larger aggregate particles. It also led to the disruption of original disulfide bonds and hydrophobic interactions within protein molecules, and the formation of new cross-links. Intriguingly, compared to native plant proteins, TVPs' α-helix/ß-sheet values decreased from 0.68 to 0.69 to 0.56-0.65. Extrusion increased the proportion of peptides shorter than 1 kD in digesta of TVPs by 1.44-23.63%. In comparison to unextruded plant proteins, TVPs exhibited lower content of free amino acids in cell transport products. Our findings demonstrated that extrusion can modify protein secondary structure by diminishing the α-helix/ß-sheet value, and impact protein tertiary structure by reducing disulfide bonds and hydrophobic interactions, promoting the digestion and absorption of plant proteins. These insights offer valuable scientific backing for the utilization of extruded plant-based proteins, bolstering their role in enhancing the palatability and nutritional profile of plant-based meat substitutes.

Distant organ metastasis patterns and prognosis of lung adenosquamous carcinoma: a SEER database analysis.

OBJECTIVES: Our purpose is to evaluate the patterns of organ metastasis and the prognosis in lung adenosquamous carcinoma patients with organ metastasis. METHODS: We collected the data from the surveillance epidemiology and end results database, covering the period of 2000-2018. Cox regression, Kaplan-Meier and log-rank analyses were performed. RESULTS: Totally, 2698 patients were enrolled, comprising 851 (31.54%) patients diagnosed with organ metastasis and 2017 (68.46%) patients without organ metastasis. Patients with distant organ metastasis show a significant decrease in median overall survival. In addition to the aforementioned factors, age over 70 years, male, main bronchus, advanced T stage, larger tumour size, absence of primary tumour surgery and lack of radiotherapy have all been identified as prognostic indicators associated with a poorer outcome. In terms of treatment options, patients with organ metastasis can benefit from chemotherapy and primary tumour surgery. Moreover, in patients with organ metastasis, those who received a combination treatment of surgery, chemotherapy and radiotherapy displayed the most favourable prognosis, with a median overall survival of 17 months. CONCLUSIONS: We identified the prognostic indicators for organ metastasis in patients with lung adenosquamous carcinoma. Highly selected patients who undergo a combination treatment of surgery, chemotherapy and radiotherapy may experience the greatest survival benefit.

Human monoclonal antibody F61 nasal spray effectively protected high-risk populations from SARS-CoV-2 variants during the COVID-19 pandemic from late 2022 to early 2023 in China.

Following the national dynamic zero-COVID strategy adjustment, the utilization of broad-spectrum nasal neutralizing antibodies may offer an alternative approach to controlling the outbreak of Omicron variants between late 2022 and early 2023 in China. This study involved an investigator-initiated trial (IIT) to assess the pharmacokinetic, safety and efficacy of the F61 nasal spray. A total of 2,008 participants were randomly assigned to receive F61 nasal spray (24 mg/0.8 mL/dose) or normal saline (0.8 mL/dose) and 1336 completed the follow-up in the IIT. Minimal absorption of F61 antibody into the bloodstream was detected in individuals receiving F61 nasal spray for seven consecutive days. No treatment-emergent adverse reactions of grade 3 severity or higher were reported. In the one-dose cohort, the 7-day cumulative SARS-CoV-2 infection rate was 79.0% in the F61 group and 82.6% in the placebo group, whereas, in the multiple-dose (once daily for 7 consecutive days) cohort, the rates were 6.55% in the F61 group and 23.83% in the placebo group. The laboratory-confirmed efficacy of F61 was 3.78% (-3.74%-10.75%) in the one-dose cohort and 72.19% (57.33%-81.87%) in the multiple-dose cohort. In the real-world study, 60,225 volunteers in four different regions were administered the F61 nasal spray based on the subject's wishes, over 90% efficacy rate was observed against different Omicron variants. The F61 nasal spray, with its favourable safety profile, could be a promising prophylactic monoclonal antibody against SARS-CoV-2 VOCs.

Promoting Intratumoral Drug Accumulation by Bio-Membrane Regulated Active Targeting for Tumor Photothermal Therapy.

Introduction: Insufficient tumor permeability and inadequate nanoparticle retention continue to be significant limitations in the efficacy of anti-tumor drug therapy. Numerous studies have focused on enhancing tumor perfusion by improvement of tumor-induced endothelial leakage, often known as the enhanced permeability and retention (EPR) effect. However, these approaches have produced suboptimal therapeutic outcomes and have been associated with significant side effects. Therefore, in this study, we prepared tumor cell membrane-coated gold nanorods (GNR@TM) to enhance drug delivery in tumors through homogeneous targeting of tumor cell membranes and in situ real-time photo-controlled therapy. Methods: Here, we fabricated GNR@TM, and characterized it using various techniques including Ultraviolet-Visible (UV-Vis) spectrophotometer, particle size analysis, potential measurement, and transmission electron microscopy (TEM). The cellular uptake and cytotoxicity of GNR@TM were analyzed by flow cytometry, confocal laser scanning microscopy (CLSM), TEM, CCK8 assay and live/dead staining. Tissue drug distribution was determined by inductively coupled plasma mass spectrometry (ICP-MS) and immunofluorescence staining. Furthermore, to evaluate the therapeutic effect, mice bearing MB49 tumors were intravenously administered with GNR@TM. Subsequently, near-infrared (NIR) laser therapy was performed, and the mice's tumor growth and body weight were monitored. Results: The tumor cell membrane coating endowed GNR@TM with extended circulation time in vivo and homotypic targeting to tumor, thereby enhancing the accumulation of GNR@TM within tumors. Upon 780 nm laser, GNR@TM exhibited excellent photothermal conversion capability, leading to increased tumor vascular leakage. This magnification of the EPR effect induced by NIR laser further increased the accumulation of GNR@TM at the tumor site, demonstrating strong antitumor effects in vivo. Conclusion: In this study, we successfully developed a NIR-triggered nanomedicine that increased drug accumulation in tumor through photo-controlled therapy and homotypic targeting of the tumor cell membrane. GNR@TM has been demonstrated effective suppression of tumor growth, excellent biocompatibility, and significant potential for clinical applications.

Translatability of In Vitro Stress for Predicting Deamidation and Oxidation Biotransformation on Biotherapeutics.

Biotransformation leading to single residue modifications (e.g., deamidation, oxidation) can contribute to decreased efficacy/potency, poor pharmacokinetics, and/or toxicity/immunogenicity for protein therapeutics. Identifying and characterizing such liabilities in vivo are emerging needs for biologics drug discovery. In vitro stress assays involving PBS for deamidation or AAPH for oxidation are commonly used for predicting liabilities in manufacturing and storage and are sometimes considered a predictive tool for in vivo liabilities. However, reports discussing their in vivo translatability are limited. Herein, we introduce a mass spectrometry workflow that characterizes in vivo oxidation and deamidation in pharmacokinetically relevant compartments for diverse protein therapeutic modalities. The workflow has low bias of <10% in quantitating degradation in the relevant pharmacokinetic concentration range for monkey and rabbit serum/plasma (1-100 µg/mL) and allows for high sequence coverage (∼85%) for discovery/monitoring of amino acid modifications. For oxidation and deamidation, the assay was precise, with percent coefficient of variation of <8% at 1-100 µg/mL and ≤6% method-induced artifacts. A high degree of in vitro and in vivo correlation was observed for deamidation on the six diverse protein therapeutics (seven liability sites) tested. In vivo translatability for oxidation liabilities were not observed for the 11 molecules tested using in vitro AAPH stress. One of the molecules dosed in eyes resulted in a false positive and a false negative prediction for in vivo oxidation following AAPH stress. Finally, peroxide stress was also tested but resulted in limited success (1 out of 4 molecules) in predicting oxidation liabilities.