Transbronchial cryoablation in peripheral lung parenchyma with a novel thin cryoprobe and initial clinical testing.

BACKGROUND: Transbronchial cryoablation shows potential as a local therapy for inoperable peripheral lung cancer. However, its clinical application for peripheral pulmonary lesions has not been reported yet. METHODS: An improved cryoprobe with an 8-mm-long, 1.9-mm-wide cryotip was used. Initially, the safety and effectiveness of this cryoprobe were assessed in an in vivo porcine model. Transbronchial cryoablation with 2 or 3 freeze-thaw cycles (10 min or 15 min in each freezing time) was performed in 18 pigs under CT monitoring. Radiological and pathological examinations were performed to evaluate the extent of cryoablation. Subsequently, nine patients with stage IA peripheral lung cancer or metastases underwent transbronchial cryoablation with this cryoprobe under the guidance of navigation bronchoscopy and cone-beam CT. Technical success, safety and outcomes were assessed. RESULTS: 36 cryoablation procedures were performed successfully without any major complications in the porcine model. The extent of cryoablation increased with freezing time and the number of freeze-thaw cycles, which peaked at 24 hours and then gradually decreased. Pathological results showed a change from massive haemorrhage at 24 hours to fibrous hyperplasia with chronic inflammation after 4 weeks. In the clinical trial, 10 cryoablations were performed on 9 tumours with a technical success rate of 100%. One mild treatment-related complication occurred. Of the nine tumours, seven achieved complete ablation, while two exhibited incomplete ablation and subsequent local progression at 6 months. CONCLUSION: Our initial experience indicated that transbronchial cryoablation was a safe and feasible procedure for non-surgical peripheral stage IA lung cancer or pulmonary metastases. TRIAL REGISTRATION NUMBER: ChiCTR2200061544.

Epidemiology and diagnosis technologies of human metapneumovirus in China: a mini review.

Human metapneumovirus (HMPV) is a newly identified pathogen causing acute respiratory tract infections in young infants worldwide. Since the initial document of HMPV infection in China in 2003, Chinese scientists have made lots of efforts to prevent and control this disease, including developing diagnosis methods, vaccines and antiviral agents against HMPV, as well as conducting epidemiological investigations. However, effective vaccines or special antiviral agents against HMPV are currently not approved, thus developing early diagnosis methods and knowing its epidemiological characteristics will be beneficial for HMPV control. Here, we summarized current research focused on the epidemiological characteristics of HMPV in China and its available detection methods, which will be beneficial to increase the public awareness and disease control in the future.

Investigation of the Interaction Between Lactones and Ketones in a Cheddar Cheese Matrix Using Feller's Additive Model, σ-τ Plots, U-Models, and Aroma Addition Experiments.

The objective of this study was to examine the sensory interactions between lactones and ketones in a cheddar simulation matrix through perceptual interaction analysis. The olfactory thresholds of 6 key lactones had values ranging from 8.32 to 58.88 µg/kg, whereas those of the 4 key ketones ranged from 6.61 to 660.69 µg/kg. Both Feller's additive model and σ-τ plots demonstrated complex interactions in 24 binary mixtures composed of the 6 lactones and 4 ketones, including synergy, addition, and masking effects. Specifically, we found that 6 binary mixtures exhibited aroma synergistic effects using both methods. Moreover, the σ-τ plot showed a synergistic effect of aroma in 3 ternary mixtures. The U-model further confirmed the synergistic effects of the 6 groups of binary systems and 3 groups of ternary systems on aroma at actual cheese concentrations. In an aroma addition experiment, the combination of δ-octalactone and diacetyl in binary mixtures had the most pronounced impact on enhancing milk flavor. In ternary mixtures, 2 combinations, namely δ-octalactone/δ-dodecalactone/diacetyl and γ-dodecalactone/δ-dodecalactone/acetoin, significantly enhanced the milky and sweet aroma properties of cheese, while also enhancing the overall acceptability of the cheese aroma.

Chromosome-level genome of black cutworm provides novel insights into polyphagy and seasonal migration in insects.

BACKGROUND: The black cutworm, Agrotis ipsilon, is a serious global underground pest. Its distinct phenotypic traits, especially its polyphagy and ability to migrate long distances, contribute to its widening distribution and increasing difficulty of control. However, knowledge about these traits is still limited. RESULTS: We generated a high-quality chromosome-level assembly of A. ipsilon using PacBio and Hi-C technology with a contig N50 length of ~ 6.7 Mb. Comparative genomic and transcriptomic analyses showed that detoxification-associated gene families were highly expanded and induced after insects fed on specific host plants. Knockout of genes that encoded two induced ABC transporters using CRISPR/Cas9 significantly reduced larval growth rate, consistent with their contribution to host adaptation. A comparative transcriptomic analysis between tethered-flight moths and migrating moths showed expression changes in the circadian rhythm gene AiCry2 involved in sensing photoperiod variations and may receipt magnetic fields accompanied by MagR and in genes that regulate the juvenile hormone pathway and energy metabolism, all involved in migration processes. CONCLUSIONS: This study provides valuable genomic resources for elucidating the mechanisms involved in moth migration and developing innovative control strategies.

Characterization of Flavor Profile of Sauced Pork from Different Regions of China Based on E-Nose, E-Tongue and Gas Chromatography-Ion Mobility Spectroscopy.

This study aimed to investigate the volatile flavor compounds and tastes of six kinds of sauced pork from the southwest and eastern coastal areas of China using gas chromatography-ion mobility spectroscopy (GC-IMS) combined with an electronic nose (E-nose) and electronic tongue (E-tongue). The results showed that the combined use of the E-nose and E-tongue could effectively identify different kinds of sauced pork. A total of 52 volatile flavor compounds were identified, with aldehydes being the main flavor compounds in sauced pork. The relative odor activity value (ROAV) showed that seven key volatile compounds, including 2-methylbutanal, 2-ethyl-3, 5-dimethylpyrazine, 3-octanone, ethyl 3-methylbutanoate, dimethyl disulfide, 2,3-butanedione, and heptane, contributed the most to the flavor of sauced pork (ROAV ≥1). Multivariate data analysis showed that 13 volatile compounds with the variable importance in projection (VIP) values > 1 could be used as flavor markers to distinguish six kinds of sauced pork. Pearson correlation analysis revealed a significant link between the E-nose sensor and alcohols, aldehydes, terpenes, esters, and hetero-cycle compounds. The results of the current study provide insights into the volatile flavor compounds and tastes of sauced pork. Additionally, intelligent sensory technologies can be a promising tool for discriminating different types of sauced pork.

Bt maize can provide non-chemical pest control and enhance food safety in China.

China is the world's second-largest maize producer and consumer. In recent years, the invasive fall armyworm Spodoptera frugiperda (J.E. Smith) has adversely affected maize productivity and compromised food security. To mitigate pest-inflicted food shortages, China's Government issued biosafety certificates for two genetically modified (GM) Bt maize hybrids, Bt-Cry1Ab DBN9936 and Bt-Cry1Ab/Cry2Aj Ruifeng 125, in 2019. Here, we quantitatively assess the impact of both Bt maize hybrids on pest feeding damage, crop yield and food safety throughout China's maize belt. Without a need to resort to synthetic insecticides, Bt maize could mitigate lepidopteran pest pressure by 61.9-97.3%, avoid yield loss by 16.4-21.3% (range -11.9-99.2%) and lower mycotoxin contamination by 85.5-95.5% as compared to the prevailing non-Bt hybrids. Yield loss avoidance varied considerably between experimental sites and years, as mediated by on-site infestation pressure and pest identity. For either seed mixtures or block refuge arrangements, pest pressure was kept below established thresholds at 90% Bt maize coverage in Yunnan (where S. frugiperda was the dominant species) and 70% Bt maize coverage in other sites dominated by Helicoverpa armigera (Hübner) and Ostrinia furnacalis (Guenée). Drawing on experiences from other crop/pest systems, Bt maize in se can provide area-wide pest management and thus, contribute to a progressive phase-down of chemical pesticide use. Hence, when consciously paired with agroecological and biodiversity-based measures, GM insecticidal crops can ensure food and nutrition security, contribute to the sustainable intensification of China's agriculture and reduce food systems' environmental footprint.

Regulation of the pleiotropic transcriptional regulator CodY on the conversion of branched-chain amino acids into branched-chain aldehydes in Lactococcus lactis.

IMPORTANCE: Branched-chain aldehydes are the primary compounds that contribute to the nutty flavor in cheddar cheese. Lactococcus lactis, which is often applied as primary starter culture, is a significant contributor to the nutty flavor of cheddar cheese due to its ability of conversion of BCAAs into branched-chain aldehydes. In the present study, we found that the regulatory role of CodY is crucial for the conversion. CodY acts as a pleiotropic transcriptional regulator via binding to various regulatory regions of key genes. The results presented valuable knowledge into the role of CodY on the regulation and biosynthetic pathway of branched-chain amino acids and the related aldehydes. Furthermore, it provided new insight for increasing the nutty flavor produced during the manufacture and ripening of cheese.

Dynamics of microbial communities associated with flavor formation during sour juice fermentation and the milk fan drying process.

Milk fan is an acid-curd cheese with strong national characteristics (a traditional dairy product of the Bai nationality with a shape like a piece of paper) and a long history in Yunnan province, China. In our previous study, we characterized the microbial community diversity of milk fan, but the succession of microorganisms associated with flavor formation in milk fan is still unknown. Therefore, we examined the predominant microorganisms and their correlations with the formation of flavor in the fermentation of sour juice and drying of milk fan by gas chromatography mass spectrometry, high-throughput 16S rDNA sequencing, intergenic spacer sequencing and metatranscriptome analysis. We found that the relative abundances of Lactobacillus and Issatchenkia initially decreased and then increased with time during the fermentation of sour juice. However, the relative abundances of Acetobacter, Leuconostoc, Lactococcus, Geotrichum, and Dipodascus initially increased and then decreased. During the drying step, the relative abundances of Lactobacillus and Issatchenkia continuously increased and became the dominant microorganisms in the milk fan. The metatranscriptomes generated from the milk fan showed that "carbohydrate metabolism," "translation," and "signal transduction" were the main metabolic functions of the microbial communities. Rhodotorula and Yarrowia contained more differentially expressed genes than other genera, which indicated they may be associated with the production of the characteristic flavor. Furthermore, a Pearson correlation analysis showed that Lactococcus, Rhodotorula, Candida, Cutaneotrichosporon, and Yarrowia were significantly positively correlated with more aroma-active compounds, mainly ethyl acetate, 2-heptanone, isovaleraldehyde, butyric acid, nonanal, and hexanal. In conclusion, these findings contribute to a better understanding of the flavor production mechanism during the production of milk fan.

Aroma Sensory Properties of Gouda Cheeses Based on Young Chinese Consumers' Preference.

The objective of this study was to examine the aroma profiles of 12 Gouda cheeses sold in China and determine which aromas were preferred by young Chinese consumers (n = 110). The consumers selected 11 descriptors of the aromas of the Gouda cheeses in a Check-All-That-Apply (CATA) questionnaire. These 11 descriptors were used by a panel of experts for sensory analysis to perform a Quantitative Descriptive Analysis (QDA) of the cheeses. A principal component analysis of the data from the QDA revealed that the characteristic aromas of the young Gouda cheeses, medium-aged Gouda cheeses and aged Gouda cheeses were "milky" and "whey"; "creamy"; and "sour," "rancid," "nutty," etc., respectively. The results of a penalty analysis combined with the CATA results and the preference scores showed that the 3 groups of young Chinese consumers (those who often ate cheese, occasionally ate cheese, and never ate cheese) preferred the Gouda cheeses with "milky" or "creamy" aromas and did not like those with "sour" or "rancid" aromas. Occasional cheese eaters comprised the majority of the young Chinese consumers, and they were more tolerant of the Gouda cheeses with "whey" and "sulfury" aromas than those who often ate cheese and those who never ate cheese. In addition, there was a positive correlation between the consumers' preferences for the aromas of the Gouda cheeses and their willingness to pay for the cheeses. Overall, the results of this study should help promote the development of Gouda cheeses and associated products that meet the preferences of young Chinese consumers.

Effect of alsD deletion and overexpression of nox and alsS on diacetyl and acetoin production by Lacticaseibacillus casei during milk fermentation.

Diacetyl and acetoin are key aroma components of fermented milk but are produced in low concentrations by starter cultures. In this study, we expressed NADH oxidase, acetolactate synthase, and inactivated acetolactate decarboxylase in Lacticaseibacillus casei TCS to generate recombinant L. casei strains, and investigated the effects of the genes encoding these enzymes on diacetyl and acetoin production during milk fermentation. In the single-gene recombinant strains tested, diacetyl concentrations were highest in milk fermented by L. casei TCSI-nox (nox gene overexpressed, 3.68 mg/kg), whereas acetoin concentrations were highest in milk fermented by L. casei TCS-ΔalsD (alsD gene deleted, 32.94 mg/kg). Moreover, diacetyl and acetoin concentrations were higher in the inducible strains than in the corresponding constitutive strains (e.g., TCSI-nox vs. TCSC-nox, and TCSI-ΔalsD-nox vs. TCSC-ΔalsD-nox). This phenomenon was also reflected in the protein expression levels and enzyme activities. In the double-gene recombinant strains tested, the highest concentrations of diacetyl and acetoin were produced by L. casei TCSI-ΔalsD-nox (nox overexpressed and alsD deleted, 4.66 mg/kg, 69.62 mg/kg, respectively). The triple-gene recombinant L. casei TCS-ΔalsD-nox-alsS produced the highest concentrations of diacetyl and acetoin, which were 2.38 and 11.19 times, respectively, the concentrations produced by the original strain. These results show that the nox, alsS, and alsD genes make key contributions to the biosynthesis of diacetyl and acetoin by L. casei. The modification of multiple genes had a synergistic effect, leading to greatly increased synthesis of diacetyl and acetoin by L. casei during its fermentation of milk.

Characterization of metabolic pathways for biosynthesis of the flavor compound 3-methylbutanal by Lactococcus lactis.

3-Methylbutanal is a key volatile compound that imparts a nutty flavor to Cheddar cheese. Lactococcus lactis has been successfully applied as a starter to increase the level of 3-methylbutanal produced during the ripening of cheese. However, the mechanism of action and genetic diversity of this bacterium for 3-methylbutanal biosynthesis remains unclear. In this study, we investigated the association between the L. lactis genotype and phenotype in the biosynthesis of 3-methylbutanal via both direct and indirect pathways. Fourteen strains of L. lactis were screened for the capacity to produce 3-methylbutanal, and strain 408 (>140 µM) produced the highest among all tested strains, which exhibited both α-keto acid decarboxylase and α-ketoacid dehydrogenase activities. Furthermore, the results of a sodium meta-arsenite inhibition experiment showed that the 3-methylbutanal-producing capacities of each strain declined to various degrees. The kdcA gene, which encodes the direct pathway component α-ketoacid decarboxylase, was detected in 4 of the 14 strains, of which only strain 408 contained the full-length gene. We then characterized the genes associated with the indirect pathway by detecting the expression levels of the pdh gene cluster, ack, and pta, which were expressed at relatively higher levels in a high-yield strain than in a low-yield strain. As a result, these L. lactis strains were divided into 3 categories according to gene diversity, gene expression, and 3-methylbutanal production. The results of this study refine our knowledge of the genetic determinants of 3-methylbutanal biosynthesis in L. lactis and explain the effect of both synthesis pathways on 3-methylbutanal production.

Effects of CcpA against salt stress in Lactiplantibacillus plantarum as assessed by comparative transcriptional analysis.

Lactiplantibacillus plantarum is frequently exposed to salt stress during industrial applications. Catabolite control protein (CcpA) controls the transcription of many genes, but its role in the response to salt stress remains unclear. In this study, we used transcriptome analyses to investigate differences in the logarithmic growth phases of Lactiplantibacillus plantarum ST-III and its ccpA-knockout mutant when grown with or without salt and glycine betaine (GB). The deletion of ccpA significantly affected bacterial growth under different conditions. Among the comparisons, the highest proportion of differentially expressed genes (64%) was observed in the comparison between the wild-type and ccpA mutant grown with NaCl, whereas the lowest proportion (6%) was observed in the comparison between the ccpA mutant strain cultures grown with NaCl alone or with GB together. Transcriptomic analyses showed that CcpA could regulate GB uptake, activate iron uptake, produce acetyl-CoA, and affect fatty acid composition to maintain membrane lipid homeostasis in the adaptation of high-salinity conditions. Conclusively, these results demonstrate the importance of CcpA as a master regulator of these processes in response to salt stress, and provide new insights into the complex regulatory network of lactic acid bacteria. KEY POINTS: • The absence of CcpA significantly affected growth of L. plantarum and its response to salt stress. • CcpA regulates compatible solutes absorption and ions transport to resist salt stress. • CcpA alters fatty acids composition to maintain membrane lipid homeostasis towards salt stress.

The Cryoablation for Peripheral Pulmonary Lesions Using a Novel Flexible Bronchoscopic Cryoprobe in the ex vivo Pig Lung and Liver.

BACKGROUND: Percutaneous cryoablation has been used for the treatment of lung cancer and has been shown to be safe and effective. However, some lung cancer lesions cannot be reached by percutaneous puncture; using bronchoscopy cryoablation is necessary in these cases. PURPOSES: To examine the efficiency and security of a flexible cryoprobe, we measured the size and temperature distribution of the frozen area (ice ball) in ex vivo pig lung and liver and the temperature of the bronchoscope. METHODS: We evaluated flexible cryoprobe cryoablation using a bronchoscope in ex vivo pig lung and a flexible cryoprobe alone in ex vivo pig liver. Seven temperature sensors were positioned at the surface of the cryoprobe and at distances of 0.3, 0.6, 0.9, 1.2, 1.5, and 1.8 cm from the cryoprobe. Two temperature sensors were positioned at the surface of the bronchoscope. The ex vivo pig lung and liver were perfused with 37°C saline and the former was inflated using a ventilator to simulate in vivo lung conditions. The whole operation is usually 2-3 freezing cycles. RESULTS: In ex vivo pig liver, probes made ice balls of 33.2 ± 0.2 mm in diameter. In ex vivo pig lung, probes made ice balls of 35.1 ± 1.7 mm in diameter. The temperature at the surface of the bronchoscope at distances of 1 and 10 cm from the cryoprobe reached 21.1 ± 0.1 and 10.5 ± 0.2°C. CONCLUSION: A flexible cryoprobe using a bronchoscope in ex vivo pig lung and liver was a sufficiently safe treatment method.

Effects of Seven Plant Essential Oils on the Growth, Development and Feeding Behavior of the Wingless Aphis gossypii Glover.

Cotton aphid Aphis gossypii Glover damages plants such as cotton directly by feeding on leaves and indirectly by transmitting viruses and excreting honeydew, which interferes with photosynthesis. The control of A. gossypii is still dominated by the frequent use of insecticides, which leads to a gradual increase in pesticide resistance in A. gossypii. Research is therefore needed on non-pesticide controls. In this study, seven plant essential oils (EOs) of Ocimum sanctum L., Ocimum basilicum L., Ocimum gratissimum L., Mentha piperita L., Mentha arvensis L., Tagetes erecta L., and Lavandula angustifolia Mill. were examined as potential controls for A. gossypii. We used life tables and electrical penetration graphs (EPG) to explore the effects of these EOs on the growth, development, and feeding behavior of A. gossypii, followed by a study of effects of the EOs on honeydew secretion by A. gossypii as a measure of their antifeedant activity. We found that the EOs of O. sanctum, M. piperita, M. arvensis and T. erecta significantly extended the pre-adult developmental period. Also, adult longevity, number of oviposition days, and total fecundity of A. gossypii treated with the EOs of M. arvensis or T. erecta were all significantly reduced. Aphids treated with the EOs of O. sanctum, M. piperita, or L. angustifolia showed significant reductions in their net reproductive rate (R0), intrinsic rate of increase (rm), and finite rate of increase (λ), and significant increases in mean generation time (T). In terms of their effects on the feeding behavior of A. gossypii, all seven EOs significantly reduced the total duration of phloem feeding (E2 waves), the number of phloem-feeding bouts, and the proportion of time spent in secretion of saliva into phloem sieve elements (E1 waves) and phloem feeding (E2). The total duration and number of E1 waves (saliva secretion) were significantly reduced by the EOs of O. sanctum, O. gratissimum, and M. arvensis. For C waves (probing in non-vascular tissues), the total duration spent in this behavior was significantly increased by the EOs of O. gratissimum, M. piperita, and L. angustifolia, but the number of such probing events was increased only by L. angustifolia EO. The EOs of O. basilicum, M. arvensis, and T. erecta significantly increased the total duration of ingestion of xylem sap (G waves), while the total time of mechanical difficulty in stylet penetration (F waves) was increased by M. arvensis. The total duration and number of the non-probing events (Np waves) were significantly increased by EOs of O. sanctum and O. basilicum. After treatment with all seven of these EOs, the area covered by honeydew was significantly reduced compared with the control. Studies have analyzed that EOs of O. sanctum, M. piperita, and T. erecta were most effective, followed by the EOs of M. arvensis and L. angustifolia, and finally the EOs of O. basilicum and O. gratissimum. In the present study, the EOs of O. sanctum, M. piperita, and T. erecta were found to have potential for the development as antifeedants of A. gossypii, and these data provide a basis for future research on non-pesticide chemical control of A. gossypii.

Impact of normalized COVID-19 prevention and control measures on lower respiratory tract infection pathogenesis in hospitalized children.

Objective: This study aimed to investigate the epidemiological characteristics of common pathogens contributing to childhood lower respiratory tract infections (LRTIs) in Xiangtan City, Hunan Province before and during the coronavirus disease 2019 (COVID-19) pandemic. Methods: A total of 11,891 enrolled patients, aged 1 month to 14 years, diagnosed with LRTIs and admitted to Xiangtan Central Hospital from January 2018 to December 2021 were retrospectively reviewed in this study. Specifically, the epidemiological characteristics of these pathogens before and during the COVID-19 pandemic were analyzed. Results: There was a significant decrease in the number of children hospitalized with LRTIs during the COVID-19 pandemic (2020-2021) compared to data from 2018 to 2019 (before the COVID-19 pandemic). Of these cases, 60.01% (7,136/11,891) were male and 39.99% (4,755/11,891) were female. 78.9% (9,381/11,891) cases occurred in children under 4 years of age. The average pathogen detection rate among 11,891 hospitalized LRTIs children was 62.19% (7,395/11,891), with the average pathogen detection rate of 60.33% (4,635/7,682) and 65.57% (2,670/4,209) before and during COVID-19 pandemic, respectively. The detection rates of adenovirus (ADV), bordetella pertussis (BP) and moraxella catarrhalis (M. catarrhalis) decreased dramatically, while the detection rates of influenza viruses (IFV), parainfluenza viruses (PIV), respiratory syncytial virus (RSV), haemophilus influenzae (H. influenzae), streptococcus pneumoniae (S. pneumoniae), and staphylococcus aureus (S. aureus) increased significantly during the COVID-19 pandemic. Overall, RSV, mycoplasma pneumoniae (MP), H. influenzae, and IFV were the major pathogens causing LRTIs in hospitalized children before and during the COVID-19 pandemic. Conclusion: Public health interventions for COVID-19 prevention are beneficial to reduce the incidence of LRTIs in children by limiting the prevalence of ADV, MP, BP, and M. catarrhalis, but which have limited restrictive effects on other common LRTIs-associated pathogens. Collectively, the data in this study comprehensively investigated the effects of COVID-19 pandemic on the epidemiological characteristics of respiratory pathogens, which will be beneficial for improving early preventive measures.

PD-L1 expression and its correlation with clinicopathological and molecular characteristics in Chinese patients with non-small cell lung cancer.

Little is known about the relationship between programmed cell death-ligand 1 (PD-L1) expression and histologic and genetic features in real-world Chinese non-small cell lung cancer patients. From November 2017 to June 2019, tumor tissues were collected from 2674 non-small cell lung cancer patients. PD-L1 expression was detected with immunohistochemistry using the 22C3 and SP263 antibodies, and patients were stratified into subgroups based on a tumor proportion score of 1%, 1% to 49%, and ≥ 50%. Genetic alterations were profiled using targeted next-generation sequencing. In the total population, 50.5% had negative PD-L1 expression (tumor proportion score < 1%), 32.0% had low-positive expression (1%-49%), and 17.5% had high-positive expression (≥50%). The PD-L1 positive rate was 39.0% in squamous cell carcinomas and 53.6% in adenocarcinomas. PD-L1 expression was higher in squamous cell carcinomas (P < .001) and lower in adenocarcinomas (P < .001). Of the overall patient population, 11.2% had Kirsten rat sarcoma viral oncogene (KRAS) mutations, 44.9% had epidermal growth factor receptor (EGFR) mutations, 2.1% had BRAF V600E mutations, 0.3% had MET exon 14 skipping mutations, 5.4% had anaplastic lymphoma kinase translocations, and 0.9% had ROS proto-oncogene 1 translocations. Patients carrying ROS proto-oncogene 1 translocations (P = .006), KRAS (P < .001), and MET (P = .023) mutations had significantly elevated expression of PD-L1, while those harboring EGFR (P < .001) mutations had lower PD-L1 expression. In our study, PD-L1 expression was significantly higher in squamous cell carcinomas and lower in adenocarcinomas, and was positively associated with MET and KRAS mutations, as well as the wild-type EGFR gene state. Nonetheless, additional studies are needed to further validate those associations and determine the clinical significance for immune checkpoint inhibitors of these factors.

Circular RNAs: characteristics, functions, mechanisms, and potential applications in thyroid cancer.

Thyroid cancer (TC) is one of the most common endocrine malignancies, and its incidence has increased globally. Despite extensive research, the underlying molecular mechanisms of TC remain partially understood, warranting continued exploration of molecular markers for diagnostic and prognostic applications. Circular RNAs (circRNAs) have recently garnered significant attention owing to their distinct roles in cancers. This review article introduced the classification and biological functions of circRNAs and summarized their potential as diagnostic and prognostic markers in TC. Further, the interplay of circRNAs with PI3K/Akt/mTOR, Wnt/ß-catenin, MAPK/ERK, Notch, JAK/STAT, and AMPK pathways is elaborated upon. The article culminates with an examination of circRNA's role in drug resistance of TC and highlights the challenges in circRNA research in TC.

Novel bispecific nanobody mitigates experimental intestinal inflammation in mice by targeting TNF-α and IL-23p19 bioactivities.

BACKGROUND: Inflammatory bowel diseases (IBDs) pose significant challenges in terms of treatment non-response, necessitating the development of novel therapeutic approaches. Although biological medicines that target TNF-α (tumour necrosis factor-α) have shown clinical success in some IBD patients, a substantial proportion still fails to respond. METHODS: We designed bispecific nanobodies (BsNbs) with the ability to simultaneously target human macrophage-expressed membrane TNF-α (hmTNF-α) and IL-23. Additionally, we fused the constant region of human IgG1 Fc (hIgG1 Fc) to BsNb to create BsNb-Fc.  Our study encompassed in vitro and in vivo characterization of BsNb and BsNb-Fc. RESULTS: BsNb-Fc exhibited an improved serum half-life, targeting capability and effector function than BsNb. It's demonstrated that BsNb-Fc exhibited superior anti-inflammatory effects compared to the anti-TNF-α mAb (infliximab, IFX) combined with anti-IL-12/IL-23p40 mAb (ustekinumab, UST) by Transwell co-culture assays. Notably, in murine models of acute colitis brought on by 2,4,6-trinitrobenzene sulfonic acid（TNBS) and dextran sulphate sodium (DSS), BsNb-Fc effectively alleviated colitis severity. Additionally, BsNb-Fc outperformed the IFX&UST combination in TNBS-induced colitis, significantly reducing colon inflammation in mice with colitis produced by TNBS and DSS. CONCLUSION: These findings highlight an enhanced efficacy and improved biostability of BsNb-Fc, suggesting its potential as a promising therapeutic option for IBD patients with insufficient response to TNF-α inhibition. KEY POINTS: A bispecific nanobody (BsNb) was created to target TNF-α and IL-23p19, exhibiting high affinity and remarkable stability. BsNb-Fc inhibited the release of cytokines in CD4+T cells during co-culture experiments. BsNb-Fc effectively alleviated colitis severity in mouse model with acute colitis induced by DSS or TNBS, outperforming the IFX&UST combination.

Antibacterial Activity and Mechanism of Oxidized Bacterial Nanocellulose with Different Carboxyl Content.

Oxidized bacterial nanocellulose (OBC) is reported to prevent microbial growth, but its antibacterial characteristics and mechanism are still unclear. Here, the antibacterial mechanism of OBC is explored by detecting and assessing the interaction of OBC with different carboxyl content on Staphylococcus aureus and Escherichia coli. The results show that OBC has strong antibacterial activity and antibiofilm activity against S. aureus and E. coli, which is positively correlated with the carboxyl content of OBC. After OBC treatment, the bacteria adhesion is inhibited and the cell membrane is destroyed leading to increased permeability. Further investigation reveals that the concentration of cyclic diguanosine monophosphate (c-di-GMP) that induced biofilm formation is significantly decreased to 1.81 pmol mg-1 after OBC treatment. In addition, OBC inactivates mature biofilms, with inactivation rates up to 79.3%. This study suggests that OBC has excellent antibacterial and antiadhesion properties, which can increase the cell membrane permeability and inhibit c-di-GMP formation. In addition, OBC also has a strong inactivation effect on mature biofilm, which can be used as an effective antibiofilm agent.

Rapid identification of adulteration in raw bovine milk with soymilk by electronic nose and headspace-gas chromatography ion-mobility spectrometry.

The adulteration of soymilk (SM) into raw bovine milk (RM) to gain profit without declaration could cause a health risk. In this study, electronic nose (E-nose) and headspace-gas chromatography ion-mobility spectrometry (HS-GC-IMS) were applied to establish a rapid and effective method to identify adulteration in RM with SM. The obtained data from HS-GC-IMS and E-nose can distinguish the adulterated samples with SM by principal component analysis. Furthermore, a quantitative model of partial least squares was established. The detection limits of E-nose and HS-GC-IMS quantitative models were 1.53% and 1.43%, the root mean square errors of prediction were 0.7390 and 0.5621, the determination coefficients of prediction were 0.9940 and 0.9958, and the relative percentage difference were 10.02 and 13.27, respectively, indicating quantitative regression and good prediction performances of SM adulteration levels in RM were achieved. This research can provide scientific information on the rapid, non-destructive and effective adulteration detection for RM.