LC-MS/MS method for dual-ligand peptide-drug CBP-1018 and its deconjugated payload MMAE including sample stabilization strategy for its MC-Val-Cit-PABC linker.

Recently, peptide-drug conjugate (PDC) has become the most promising conjugated drug for tumor therapy after antibody-drug conjugate due to stronger tumor penetration capacity and lower immunogenicity. CBP-1018 was a PDC with dual-ligand conjugated to MMAE via a cleavable linker (MC-Val-Cit-PABC) that can be lysed by cathepsins B. In this study, two specific LC-MS/MS methods were developed and validated for the determination of CBP-1018 and its metabolite MMAE in human plasma. To prevent the cleavable MC-Val-Cit-PABC linker from degradation, a protease inhibitor (cOmplete solution) was added to the pre-cooled vacuum tubes and the separated plasma samples. The assays involved the pretreatment of CBP-1018 by protein precipitation with H2O-ACN (1:9, v/v) and the extraction of MMAE by liquid-liquid extraction with ethyl acetate under alkaline condition to eliminate the interference of CBP-1018 on MMAE. The two analytes showed good linearities over the calibration ranges (R2 ≥ 9980). Both accuracy and precision met the acceptance criteria. The validated methods were successfully applied to the phase I dose-escalation study of CBP-1018 injection in Chinese patients with solid tumors to evaluate the pharmacokinetic properties of CBP-1018 and MMAE. The results showed that CBP-1018 was eliminated immediately after injection and MMAE reached the maximum exposure at approximately 2 h after infusion. The maximum concentration of MMAE did not exceed 20.0 ng/mL, suggesting that the off-target toxicity of CBP-1018 injection was controllable.

Enhancing storage stability of pea peptides through encapsulation in maltodextrin and gum tragacanth via monitoring scavenge ability to free radicals.

Pea peptides can lead to degradation through oxidation, deamidation, hydrolysis, or cyclization during production, processing, and storage, which in turn limit their broader application. To stabilize pea peptides, this study employed spray drying technology to create a pea peptide micro-encapsule using maltodextrin, gum tragacanth, and pea peptides. Four key factors, including polysaccharide ratio, glycopeptide ratio, solid-liquid ratio, and inlet temperature, were optimized to enhance the antioxidant properties of the pea peptide micro-encapsule. The results indicated that the utilization of maltodextrin and gum tragacanth significantly improves the storage stability and antioxidant activity of pea peptides. Moreover, optimal storage stability for pea peptides was achieved with a polysaccharide ratio of 9:1, a glycopeptide ratio of 10:1, a solid-liquid ratio of 4:40, and an inlet temperature of 180 °C. After 60 days of storage, the encapsulated pea peptides maintained 70.22 %, 25.19 %, and 40.32 % for scavenging abilities to hydroxyl radical, superoxide anion, and ABTS radical, respectively. In contrast, the unencapsulated pea peptides showed a decline to 47.02 %, 0 %, and 24.46 % in the same antioxidant activities after storage. These findings underscore the potential of spray drying technology to enhance the functional properties of pea peptides for various applications.

Molecular alterations and prognosis of breast cancer with cutaneous metastasis.

PURPOSE: Cutaneous metastasis (CM) accounts for 5-30% of patients with breast cancer (BC) and presents unfavorable response to treatment and poor prognosis. A better understanding of the molecular alterations involved in metastasis is essential, which would help identify diagnostic and efficacy biomarkers for CM. MATERIALS: We retrospectively reviewed a total of 13 patients with histological or cytological diagnosis of breast cancer and CM. Clinical information was extracted from the medical records. The mutational landscape of matched primary tumors with their lymph nodes or CM tissues were analyzed using next-generation sequencing (NGS) of 425 cancer-relevant genes. All tissues were also analyzed by immunohistochemistry (IHC). The association of prognosis with various clinical and molecular factors was also evaluated. RESULTS: More than half of the patients were Ki67 low (< 50%, 53.7%). Most patients (12, 92.3%) had other metastasis sites other than skin. The median time from diagnosis to the presentation of CM (T1) was 15 months (range: 0-94 months) and the median time from CM to death (T2) was 13 months (range 1-78). The most frequently altered genes across the three types of tissues were TP53 (69.6%, 16/23), PIK3CA (34.8%, 8/23), and MYC (26.1%). The number of alterations in CM tends to be higher than in primary tumors (median 8 vs. 6, P = 0.077). Copy number loss in STK11, copy number gain in FGFR4, TERT, AR, FLT4 and VEGFA and mutations in ATRX, SRC, AMER1 and RAD51C were significantly enriched in CM (all P < 0.05). Ki67 high group (> 50%) showed significantly shorter T1 than the Ki67 low group (≤ 50%) (median 12.5 vs. 50.0 months, P = 0.036). TP53, PIK3CA mutations, and TERT amplification group were associated with inferior T2 (median 11 vs. 36 months, P = 0.065; 8 vs. 36 months, P = 0.013, 7 vs. 36 months, P = 0.003, respectively). All p values were not adjusted. CONCLUSION: We compared the genomic features of primary breast cancer tissues with their corresponding CM tissues and discussed potential genes and pathways that may contribute to the skin metastasis of advanced breast cancers patients. TP53, PIK3CA mutant, and TERT amplification may serve as biomarkers for poor prognosis for CM patients.

LINC01432 binds to CELF2 in newly diagnosed multiple myeloma promoting short progression-free survival to standard therapy.

Multiple Myeloma (MM) is a highly prevalent and incurable form of cancer that arises from malignant plasma cells, with over 35,000 new cases diagnosed annually in the United States. While there are a growing number of approved therapies, MM remains incurable and nearly all patients will relapse and exhaust all available treatment options. Mechanisms for disease progression are unclear and in particular, little is known regarding the role of long non-coding RNAs (lncRNA) in mediating disease progression and response to treatment. In this study, we used transcriptome sequencing to compare newly diagnosed MM patients who had short progression-free survival (PFS) to standard first-line treatment (PFS < 24 months) to patients who had prolonged PFS (PFS > 24 months). We identified 157 differentially upregulated lncRNAs with short PFS and focused our efforts on characterizing the most upregulated lncRNA, LINC01432. We investigated LINC01432 overexpression and CRISPR/Cas9 knockdown in MM cell lines to show that LINC01432 overexpression significantly increases cell viability and reduces apoptosis, while knockdown significantly reduces viability and increases apoptosis, supporting the clinical relevance of this lncRNA. Next, we used individual-nucleotide resolution cross-linking immunoprecipitation with RT-qPCR to show that LINC01432 directly interacts with the RNA binding protein, CELF2. Lastly, we showed that LINC01432-targeted locked nucleic acid antisense oligonucleotides reduce viability and increases apoptosis. In summary, this fundamental study identified lncRNAs associated with short PFS to standard NDMM treatment and further characterized LINC01432, which inhibits apoptosis.

Effects of Freshwater Acidification on the Gut Microbial Community of Trachemys scripta elegans.

Freshwater acidification (FA) has become a global environmental problem, posing a potential threat to freshwater ecosystems. The gut microbiota plays a crucial role in the host's response and adaptation to new environments. In this study, we investigated the changes in microbial communities in Red-eared slider (Trachemys scripta elegans) under acidic conditions to reveal the ecological impacts of acidification on freshwater turtles. The results showed that there were significant differences in ß-diversity (p = 0.03), while there were no significant differences in the α-diversity of gut microbiota in T. s. elegans between the different levels of acidification (pH of 5.5, 6.5, 7.5). Both the Gut Microbiome Health Index (GMHI) and the Microbial Dysbiosis Index (MDI) exhibited significant differences when comparing environments with a pH of 5.5 to those with a pH of 6.5 (p < 0.01). A comparative analysis between pH levels of 5.5 and 6.5 also revealed substantial differences (p < 0.01). Likewise, a comparative analysis between pH levels of 6.5 and 7.5 also revealed substantial differences (p < 0.01). At the phylum level, Firmicutes, Fusobacteria, and Bacteroidota formed a major part of the gut microbial community, Fusobacteria showed significant differences in different acidity environments (p = 0.03). At the genus level, Cetobacterium, Turicibacter, unclassified Eubacteriaceae, and Anaerorhabdus_furcosa_group showed significant differences in different acidity environments. The pH reduced interactivity in the gut microbiota of T. s. elegans. In addition, LEfSe analysis and functional prediction revealed that the potentially_pathogenic and stress_tolerant functional characteristics also showed significant differences in different acidity environments. The findings underscore the pivotal role of the gut microbiota in T. s. elegans in response to freshwater acidification and provide a foundation for further exploration into the impacts of acidification on freshwater ecosystems.

A down-regulated cytochrome P450 in Neoseiulus barkeri Hughes (Acari: Phytoseiidae) can dechlorinate and hydroxylate chlorpyrifos without producing chlorpyrifos-oxon.

Selection of chemical-resistant predatory mites is a good alternative to balance the contradiction between chemical control and biological control. Previously, a resistant strain of Neoseiulus barkeri for chlorpyrifos was obtained. In the current study, two up-regulated (NbCYP3A6, NbCYP3A16) and one down-regulated (NbCYP3A24) P450s were screened through differential expression analysis and other detoxification-related genes such as CCEs, GST, etc. were not found. 3D modelling and molecular docking indicated that the chlorine at position 5 on the pyridine ring of chlorpyrifos, as well as a methyl group, were closest to the heme iron of the enzymes (less than 5 Å). Three active recombinant P450 proteins were heterologously expressed and metabolized with chlorpyrifos in vitro. HPLC assay showed that only NbCYP3A24 could metabolize chlorpyrifos, with a metabolism rate of 21.60 %. Analysis of the m/z of metabolites by LC-MS/MS showed that chlorine at the 5C position of chlorpyrifos was stripped and hydroxylated, whereas chlorpyrifos-oxon, a common product of oxidation by P450, was not found. Knockdown of the NbCYP3A24 gene in the susceptiblestrain did reduce the susceptibility of N. barkeri to chlorpyrifos, suggesting that the biological activity of the metabolite may be similar to chlorpyrifos-oxon, thus enhancing the inhibitory effect on the target.

Microbe-material hybrids for therapeutic applications.

As natural living substances, microorganisms have emerged as useful resources in medicine for creating microbe-material hybrids ranging from nano to macro dimensions. The engineering of microbe-involved nanomedicine capitalizes on the distinctive physiological attributes of microbes, particularly their intrinsic "living" properties such as hypoxia tendency and oxygen production capabilities. Exploiting these remarkable characteristics in combination with other functional materials or molecules enables synergistic enhancements that hold tremendous promise for improved drug delivery, site-specific therapy, and enhanced monitoring of treatment outcomes, presenting substantial opportunities for amplifying the efficacy of disease treatments. This comprehensive review outlines the microorganisms and microbial derivatives used in biomedicine and their specific advantages for therapeutic application. In addition, we delineate the fundamental strategies and mechanisms employed for constructing microbe-material hybrids. The diverse biomedical applications of the constructed microbe-material hybrids, encompassing bioimaging, anti-tumor, anti-bacteria, anti-inflammation and other diseases therapy are exhaustively illustrated. We also discuss the current challenges and prospects associated with the clinical translation of microbe-material hybrid platforms. Therefore, the unique versatility and potential exhibited by microbe-material hybrids position them as promising candidates for the development of next-generation nanomedicine and biomaterials with unique theranostic properties and functionalities.

Extracorporeal membrane oxygenation states basilar artery thrombectomy and left posterior cerebral artery stent thrombectomy: A case report.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a new type of extracorporeal respiratory and circulatory assistance device. It can drain venous blood out of the body and inject it into veins or arteries after being oxygenated by an oxygenator (membrane lung) to replace lung and heart functions in a short time. ECMO can provide tissue blood perfusion and gas exchange almost equivalent to cardiac output and extend the effective treatment time window for patients with acute circulatory failure to restore cardiopulmonary function. CASE SUMMARY: We report a case of an 81-year-old woman who underwent whole cerebral angiography, basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain after implantation of ECMO. The patient was admitted to the hospital due to myocardial infarction. Considering that the cause of the patient's disturbance of consciousness was unknown and cerebrovascular accident could not be ruled out after the implantation of ECMO, the department of Radioactive Intervention performed cerebral angiography. And the result of the angiography indicated vascular occlusion. After the basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain, the patency of the occlusive vessel was achieved. CONCLUSION: Although the patient eventually died of circulatory failure, the result of this case verifies the feasibility of cerebral angiography and thrombectomy in patients with implanted ECMO in the intubated state.

Q48K mutation in the type IB nitroreductase NrmA is responsible for nitrofurantoin resistance in Enterococcus faecium.

Nitrofurantoin is recommended as first-line therapy for the optimal treatment of uncomplicated urinary tract infections (UTIs) caused by enterococci and Escherichia coli. The mutations in nfsA and nfsB genes encoding nitroreductases can lead to nitrofurantoin resistance in gram-negative bacteria. However, the mechanisms of nitrofurantoin resistance in enterococci have not been elucidated. In this study, a total of 128 clinical isolates of Enterococcus faecium were collected from patients with UTIs and 59 (46.1%) isolates were resistant to nitrofurantoin. By analyzing the whole-genome sequences of E. faecium in the NCBI database, a type IB nitroreductase was found in all E. faecium strains and designated nrmA, representing nitroreductase in E. faecium. Nitroreductase NrmA shared 18.7% sequence identity with nitroreductase NfsB in E. coli. Different from NrmA in nitrofurantoin-susceptible E. faecium, NrmA in nitrofurantoin-resistant E. faecium had one amino acid substitution, i.e., a lysine instead of a glutamine at position 48 (Q48K mutation). This mutation was located in conserved regions, which might include the flavin mononucleotide binding site, in NfsB and other nitroreductases in gram-negative bacteria. Complementation assays of nitrofurantoin-resistant E. faecium HS17-112 showed that the nitrofurantoin minimal inhibitory concentration of the complemented strain HS17-112: pIB166-nrmA (wild type [WT]) reduced from 128 mg/L to 4 mg/L. Compared with NrmA(WT), NrmA(Q48K) showed poor catalytic efficiency for nitrofurantoin. The kcat/Km of NrmA(Q48K) for nitrofurantoin decreased from 0.122 µM-1 s-1 to 0.000042 µM-1 s-1. In conclusion, the Q48K mutation of the nitroreductase NrmA is responsible for nitrofurantoin resistance in E. faecium.

Influence of short-term hypoxia exposure on dynamic visual acuity.

Background: To quantify the changes in dynamic visual acuity (DVA) and explain the hidden reasons after acute exposure to hypobaric hypoxia status. Methods: The study group comprised 18 healthy male and 15 healthy female participants aged 20-24 years old. DVA was measured with the self-developed software of Meidixin (Tianjin) Co., Ltd. Measurements were taken at eight altitudes. Data analysis was performed using the Kolmogorov-Smirnov test, paired sample T-test, and two-way repeated measures analysis of variance (ANOVA) for repeated measurements. Results: At constant altitude, DVA showed an overall decreasing trend with increasing angular velocity and a fluctuating decrease at the vast majority of altitudes. At constant angular velocities, DVA gradually increased with altitude, with the most pronounced increase in DVA at altitude 5, and thereafter a gradual decrease in DVA as altitude increased. Finally, as altitude decreased, DVA increased again and reached a higher level at the end of the experiment, which was superior to the DVA in the initial state. Conclusion: Under a hypobaric hypoxic environment at high altitude, DVA was affected by the angular velocity and the degree of hypoxia, manifesting as an increase or decrease in DVA, which affects the pilot's observation of the display and control interfaces during the driving process, acquisition of information, and decision-making ability, which in turn may potentially jeopardize the safety of the flight.

Identification and Functional Characterization of Carboxylesterase Genes Involved in Spirodiclofen Resistance in Panonychus citri (McGregor).

Overexpression of carboxyl/cholinesterase (CCE) genes has been reported to be associated with many cases of pesticide resistance in arthropods. However, it has been rarely documented that CCE genes participate in spirodiclofen resistance in Panonychus citri. In previous research, we found that spirodiclofen resistance is related to increased P450 and CCE enzyme activities in P. citri. In this study, we identified two CCE genes, PcCCE3 and PcCCE5, which were significantly upregulated in spirodiclofen-resistant strain and after exposure to spirodiclofen. RNA interference of PcCCE3 and PcCCE5 increased the spirodiclofen susceptibility in P. citri. In vitro metabolism indicated that PcCCE3 and PcCCE5 could interact with spirodiclofen, but metabolites were detected only in the PcCCE3 treatment. Our results indicated that PcCCE3 participates in spirodiclofen resistance through direct metabolism, and PcCCE5 may be involved in the spirodiclofen resistance by passive binding and sequestration, which provides new insights into spirodiclofen resistance in P. citri.

Central lean mass distribution and the risks of all-cause and cause-specific mortality in 40283 UK Biobank participants.

Introduction The purpose of this study is to investigate the association of central lean mass distribution with the risk of mortality. Methods This cohort study included 40283 UK Biobank participants. Cox proportional hazards regression models were used to estimate the association of central lean mass distribution, i.e., trunk-to-leg lean mass ratio, assessed by dual energy X-ray absorptiometry, with the risk of mortality. Results The median age of the participants was 65 years and 52% were women. During a median follow-up of 4.18 years, 674 participants died, of whom 366 were due to cancer, and 126 were due to cardiovascular causes. Compared with the lowest tertile of a trunk-to-leg lean mass ratio, the multivariable-adjusted (age, sex, ethnicity, lifestyle, comorbidities, body mass index, and appendicular muscle mass index) hazards ratios of the highest tertile of trunk-to-leg lean mass ratio were 1.55 (95%CI, 1.23 - 1.94), 1.69 (95%CI, 1.26 - 2.26), and 1.14 (95%CI, 0.72 - 1.80) for all-cause, cancer and cardiovascular mortality, respectively. Neutrophil-to-lymphocyte ratio mediated 9.3% (95% CI, 3.3%-40.4%) of the association of trunk-to-leg lean mass ratio with all-cause mortality. There was evidence for additive interactions of trunk-to-leg lean mass ratio with older age and poor diet quality for all-cause mortality. Conclusion Trunk-to-leg lean mass ratio, assessed by dual energy X-ray absorptiometry, was positively associated with the risks of all-cause and cancer mortality, independent of general obesity and central obesity, in UK middle-aged and older adults. Central lean mass distribution may interact synergistically with aging, and poor diet quality to further increase the risk of death.

Centipeda minima and 6-O-angeloylplenolin enhance the efficacy of immune checkpoint inhibitors in non-small cell lung cancer.

BACKGROUND: Chemotherapeutic agents including cisplatin, gemcitabine, and pemetrexed, significantly enhance the efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) by increasing PD-L1 expression and potentiating T cell cytotoxicity. However, the low response rate and adverse effects limit the application of chemotherapy/ICI combinations in patients. METHODS: We screened for medicinal herbs that could perturb PD-L1 expression and enhance T cell cytotoxicity in the presence of anti-PD-L1 antibody, and investigated the underlying mechanisms. RESULTS: We found that the aqueous extracts of Centipeda minima (CM) significantly enhanced the cancer cell-killing activity and granzyme B expression level of CD8+ T cells, in the presence of anti-PD-L1 antibody. Both CM and its active component 6-O-angeloylplenolin (6-OAP) upregulated PD-L1 expression by suppressing GSK-3ß-ß-TRCP-mediated ubiquitination and degradation. CM and 6-OAP significantly enhanced ICI-induced reduction of tumor burden and prolongation of overall survival of mice bearing NSCLC cells, accompanied by upregulation of PD-L1 and increase of CD8+ T cell infiltration. CM also exhibited anti-NSCLC activity in cells and in a patient-derived xenograft mouse model. CONCLUSIONS: These data demonstrated that the induced expression of PD-L1 and enhancement of CD8+ T cell cytotoxicity underlay the beneficial effects of 6-OAP-rich CM in NSCLCs, providing a clinically available and safe medicinal herb for combined use with ICIs to treat this deadly disease.

Analysis of the adhesion mechanism of functionalized carbon nanotubes by molecular dynamics simulation.

Although a lot of research has been carried out on the adhesion mechanism of gecko bristles, the research on materials inspired by gecko bristles is still limited to the design of geometric structure and the optimization of preparation process, and the adhesion mechanism of materials is still unclear. In this paper, the molecular structure of the end of the bristle-like material is focused on, and the interaction between functional group modified carbon nanotubes and the interface is analyzed by molecular dynamics simulation. Thus, the influence of different polar functional groups on the interfacial force between carbon nanotubes and silica is revealed, and the adhesion enhancement mechanism of polar groups on the interface between carbon nanotubes and silica is further verified.

Three-dimensional printing the navigation template for precise percutaneous renal puncture to treat pyonephrosis on a porcine model and a patient ：a case report.

Objective: Percutaneous nephrolithotomy (PCNL) is the main method for pyonephrosis or lithotripsy in urology. However, it often comes with high risk, as the inaccurate puncture inevitably causes bleeding, intra- and post-operative complications. So, a new inter-disciplinary approach is needed to perform the puncture more accurately. Methods: 3 signs made of lead were marked onto the skin of the posterior side of the waist of a domestic pig or a patient, which was scanned by computed tomography (CT). Based on the CT images, the computer design and the 3D printing, a navigation template made of the transparent resin material is constructed. They were attached onto the surgical area on pig or patient according to the signs. During the PCNL, with this template, the puncture position, angle and depth were optimized in order to precisely enter the targeted renal pelvis or calices. Results: With the 3D navigation templates, 18G puncture needles were used to enter the renal pelvis upon performing the PCNL on a porcine model and a patient. On the porcine model, the urine outflow was observed with minimal complication. Post-operative CT scans revealed that the needle was located in the renal pelvis. For the patient case, the puncture point was designed to target the calix with stone. No obvious bleeding and complication was found in renal puncture with template. Conclusions: The navigation template was made with the combination of 3D printing, CT images and computer design. This template allows for accurate puncture of the renal pelvis or calix. Surgical improvement in kidney stones and pyonephrosis was observed in porcine model and patient case. In the future, prospective, trandomized, controlled clinical trials are needed to further confirm its advantage.

Inadequate Glucagon Suppression During OGTT in prediabetes: A Systematic Review and Meta-Analysis.

CONTEXT: Glucagon plays a role in the development of type 2 diabetes, yet its role in prediabetes (preDM) remains uncertain. OBJECTIVE: To evaluate glucagon levels in fasting state and its response to glucose inhibition in preDM through meta-analysis. METHODS: A systematic search across Pubmed, Embase, Web of Science, and Cochrane Library identified studies assessing glucagon levels during 75g oral glucose tolerance test (OGTT) in both preDM and normal glucose tolerance (NGT) cohorts. Data on glucagon, glucose and insulin were pooled using random-effect model. RESULTS: Although glucagon levels decreased in both preDM and NGT groups upon glucose challenge, glucagon levels at 0h, 0.5h, 1h and 1.5h in preDM were significantly higher compared to NGT, despite higher glucose levels at all time points and higher insulin levels at 0h, 1h, 1.5h and 2h during OGTT. Subgroup analysis revealed that in studies using the radioimmunoassay (RIA) method, glucagon levels in preDM were higher at 0.5h and 1h than NGT, while in studies using the Enzyme linked immunosorbent assay (ELISA) method, glucagon levels were similar to those of the NGT group despite higher glucose in preDM compared to NGT. Fasting glucagon level was inadequately suppressed in both impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Responsiveness to glucose inhibition was preserved in IFG, while glucagon level in IGT group at 0.5h after glucose intake was not suppressed and was higher than NGT. CONCLUSION: Glucagon was not adequately suppressed during OGTT in preDM. Glucagon dysregulation is a contributing mechanism underlying both IFG and IGT.

Complex evolutionary trajectories in vivo of two novel KPC variants conferring ceftazidime-avibactam resistance.

More and more ceftazidime-avibactam resistant KPC-producing K. pneumoniae have been reported with its widespread use, and the detection rate of KPC variants has increased dramatically. However, the evolutionary mechanism and fitness effects during KPC mutation remained unknown. Here, we report the complex in vivo evolutionary trajectories of two novel KPC variants, KPC-155 (L169P/GT242A) and KPC-185 (D179Y/GT242A), from Klebsiella pneumoniae in the same patient. The novel variants were shown to confer ceftazidime-avibactam resistance but restore carbapenem susceptibility based on the results of plasmid transformation assays, cloning experiments, and enzyme kinetic measurements. In vitro competition experiments highlighted the adaptive advantage conferred by strains carrying these KPC variants, which could lead to the rapid spread of these ceftazidime-avibactam resistant strains. The growth curve indicated that blaKPC-185 had better growth conditions at lower avibactam concentration compared to blaKPC-155, which was consistent with ceftazidime-avibactam use in vivo. In addition, replicative transposition of the IS26-flanked translocatable unit (IS26-ISKpn6-blaKPC-ISKpn27-IS26) also contributes to the blaKPC amplification and formation of two copies (blaKPC-2 and blaKPC-185), conferring both carbapenem and ceftazidime-avibactam resistance. However, strains with double copies showed reduced competitive advantage and configuration stability. The comparative plasmid analysis of IS26 group (IS26-blaKPC-IS26) and Tn1721 group (Tn1721-blaKPC-IS26) revealed that IS26-insertion could influence the distribution of resistance genes and ability of self-conjugation. The dynamic changes in blaKPC configuration highlight the need for consistent monitoring including antimicrobial susceptibility testing and determination of blaKPC subtypes-during clinical treatment, especially when ceftazidime-avibactam is administered.

A method for calculating vector forces at human-mattress interface during sleeping positions utilizing image registration.

The vector forces at the human-mattress interface are not only crucial for understanding the distribution of vertical and shear forces exerted on the human body during sleep but also serves as a significant input for biomechanical models of sleeping positions, whose accuracy determines the credibility of predicting musculoskeletal system loads. In this study, we introduce a novel method for calculating the interface vector forces. By recording indentations after supine and lateral positions using a vacuum mattress and 3D scanner, we utilize image registration techniques to align body pressure distribution with the mattress deformation scanning images, thereby calculating the vector force values for each unit area (36.25 mm × 36.25 mm). This method was validated through five participants attendance from two perspectives, revealing that (1) the mean summation of the vertical force components is 98.67% ± 7.21% body weight, exhibiting good consistency, and mean ratio of horizontal component force to body weight is 2.18% ± 1.77%. (2) the predicted muscle activity using the vector forces as input to the sleep position model aligns with the measured muscle activity (%MVC), with correlation coefficient over 0.7. The proposed method contributes to the vector force distribution understanding and the analysis of musculoskeletal loads during sleep, providing valuable insights for mattress design and evaluation.

Embedded monitoring system and teaching of artificial intelligence online drug component recognition.

Drug testing has many test elements. It aims to prevent unqualified drugs from entering the market and ensure drug safety. The existing artificial intelligence (AI) online monitoring system identifies active ingredients in the process of use. Owing to their openness, data are easy to be lost, failing to meet user needs and inducing a specific impact on the use of the monitoring system. With the continuous development of computer and measurement technologies, various biochemical data are increasing at an unprecedented speed, and numerous databases are emerging. Extracting patterns from considerable known data and experimental facts is an essential task for a wide range of biological and chemical workers. Pattern recognition is one of the essential technologies for data mining. It is widely used in industry, agriculture, national defense, biomedicine, meteorology, astronomy, and other fields. To improve the effect of the online drug ingredient recognition system, this study used AI to design an online drug ingredient recognition-embedded monitoring system and applied AI to the teaching field to improve teaching efficiency. First, this study constructed the framework of the AI online drug ingredient recognition-embedded monitoring system and introduced the process of online drug ingredient recognition. Then, it introduced the pattern recognition method, constructed the pattern recognition system, and presented the pattern recognition algorithm and the algorithm evaluation index. Afterward, it used pattern recognition to conduct a qualitative analysis of the infrared spectrum of drug components and introduced the overall process of the qualitative analysis. In addition, this study employed AI to implement changes to the embedded system instruction in colleges and universities, summarizing the current issues. The impact of drug component recognition and the educational impact of embedded systems were investigated in the experimental portion. The experimental findings demonstrated the excellent accuracy, sensitivity, specificity, and Matthew correlation coefficient of the online drug component recognition-integrated monitoring system in this work. Compared with that of other systems, its average drug component recognition accuracy was above 0.85. Students in five majors reported high levels of satisfaction with the embedded system teaching, which is better for delivering college instruction.