Investigating shared genetic architecture between inflammatory bowel diseases and primary biliary cholangitis.

Background & Aims: Inflammatory bowel disease (IBD) is commonly associated with extraintestinal complications, including autoimmune liver disease. The co-occurrence of IBD and primary biliary cholangitis (PBC) has been increasingly observed, but the underlying relationship between these conditions remains unclear. Methods: Using summary statistics from genome-wide association studies (GWAS), we investigated the causal effects between PBC and IBD, including Crohn's disease (CD) and ulcerative colitis (UC). We also analyzed the shared genetic architecture between IBD and PBC using data from GWAS, bulk-tissue RNA sequencing, and single cell RNA sequencing, and explored potential functional genes. Result: There was a strong positive genetic correlation between PBC and IBD (linkage disequilibrium score regression: rg = 0.2249, p = 3.38 × 10-5). Cross-trait analysis yielded 10 shared-risk single nucleotide polymorphisms (SNPs), as well as nine novel SNPs, which were associated with both traits. Using Mendelian randomization, a stable causal effect was established of PBC on IBD. Genetically predicted PBC was found to have a risk effect on IBD (1.105; 95% CI: 1.058-1.15; p = 1.16 × 10-10), but not vice versa. Shared tissue-specific heritability enrichment was identified for PBC and IBD (including CD and UC) in lung, spleen, and whole-blood samples. Furthermore, shared enrichment was observed of specific cell types (T cells, B cells, and natural killer cells) and their subtypes. Nine functional genes were identified based on summary statistics-based Mendelian randomization. Conclusions: This study detected shared genetic architecture between IBD and PBC and demonstrated a stable causal relationship of genetically predicted PBC on the risk of IBD. These findings shed light on the biological basis of comorbidity between IBD and PBC, and have important implications for intervention and treatment targets of these two diseases simultaneously. Impact and Implications: The discovery of novel shared single nucleotide polymorphisms (SNPs) and functional genes provides insights into the common targets between inflammatory bowel disease (IBD) and primary biliary cholangitis (PBC), serving as a basis for new drug development and contributing to the study of disease pathogenesis. Additionally, the established significant causality and genetic correlation underscore the importance of clinical intervention in preventing the comorbidity of IBD and PBC. The enrichment of SNP heritability in specific tissues and cell types reveals the role of immune factors in the potential disease mechanisms shared between IBD and PBC. This stimulates further research on potential interventions and could lead to the development of new targets for immune-based therapies.

Ultrasonic-assisted green extraction and incorporation of Spirulina platensis bioactive components into turmeric essential oil-in-water nanoemulsion for enhanced antioxidant and antimicrobial activities.

The utilization of essential oils as natural antioxidants and preservatives is limited by high volatility, poor water solubility, and long-term instability. To address this, a novel ultrasonic-assisted method was used to prepare and stabilize a nanoemulsion of turmeric essential oil-in-water, incorporating bioactive components extracted from Spirulina platensis. Ultrasonic treatment enhanced the extraction efficacy and nanoemulsion stability. Algal biomass subjected to ultrasonic treatment (30 min at 80% amplitude) yielded a dry extract of 73.66 ± 3.05%, with the highest protein, phenolic, phycocyanin, and allophycocyanin content, as well as maximum emulsifying activity. The resulting nanoemulsion (5% oil, 0.3% extract, 10 min ultrasonic treatment) showed reduced particle size (173.31 ± 2.24 nm), zeta potential (-36.33 ± 1.10 mV), low polydispersity index, and enhanced antioxidant and antibacterial properties. Rheology analysis indicated shear-thinning behavior, while microscopy and spectroscopy confirmed structural changes induced by ultrasonic treatment and extract concentration. This initiative developed a novel ultrasonic-assisted algal-based nanoemulsion with antioxidant and antibacterial properties.

The effects of inulin on solubilizing and improving anti-obesity activity of high polymerization persimmon tannin.

High polymerization persimmon tannin has been reported to have lipid-lowering effects. Unfortunately, the poor solubility restricts its application. This research aimed to investigate the effect and mechanism of inulin on solubilizing of persimmon tannin. Furthermore, we examined whether the addition of inulin would affect the attenuated obesity effect of persimmon tannin. Transmission electron microscope (TEM), Isothermal titration calorimetry (ITC) and Fourier transform infrared spectroscopy (FT-IR) results demonstrated that inulin formed a gel-like network structure, which enabled the encapsulation of persimmon tannin through hydrophobic and hydrogen bond interactions, thereby inhibiting the self-aggregation of persimmon tannin. The turbidity of the persimmon tannin solution decreased by 56.2 %, while the polyphenol content in the supernatant increased by 60.0 %. Furthermore, biochemical analysis and 16s rRNA gene sequencing technology demonstrated that persimmon tannin had a significant anti-obesity effect and improved intestinal health in HFD-fed mice. Moreover, inulin was found to have a positive effect on enhancing the health benefits of persimmon tannin, including improving hepatic steatosis and gut microbiota dysbiosis. it enhanced the abundance of beneficial core microbes while decreasing the abundance of harmful bacteria. Our findings expand the applications of persimmon tannin in the food and medical sectors.

Moxibustion ameliorates ovarian function in premature ovarian insufficiency rats by activating cAMP/PKA/CREB to promote steroidogenesis in ovarian granulosa cells.

Premature ovarian insufficiency (POI) presents a substantial challenge to women's physiological and psychological well-being. Hormone replacement therapy, as the preferred therapeutic approach, involves solely exogenous supplementation of estrogen. Moxibustion, a traditional Chinese external treatment, has been investigated in our previous studies. It not only improves hormone levels and clinical symptoms in POI patients but also safeguards ovarian reserve. This study aims to explore the regulatory mechanisms by which moxibustion modulates hormone levels and restores ovarian function in POI. A POI rat model was established using cyclophosphamide, and moxibustion treatment was applied at acupoints "CV4" and "SP6" for a total of four courses. Subsequently, ovaries from each group were subjected to transcriptome sequencing (Bulk RNA-seq). Target pathways and key genes were selected through enrichment analysis and GSVA scoring, with validation using various techniques including electron microscopy, ELISA, Western blot, and immunohistochemistry. The results demonstrated that moxibustion restored the estrous cycle in POI rats, improved sex hormone levels, reduced the number of atretic follicles, and increased the count of dominant follicles (P<0.05). Bulk RNA-seq analysis revealed that moxibustion downregulated pathways associated with ovarian dysfunction, infertility, and immune responses, upregulated pathways related to follicular development and ovarian steroidogenesis. Furthermore, our data confirmed that moxibustion significantly increased the number of ovarian granulosa cells (GCs) and upregulated the expression of proteins related to steroidogenesis in GCs, including FSHR, P450 arom, cAMP, PKA, and CREB (P<0.05), with no significant effect observed on proteins related to steroidogenesis in theca cells. These outcomes aligned with the RNA-seq results. In conclusion, these findings propose that moxibustion enhances steroidogenesis in GCs through the activation of the cAMP/PKA/CREB pathway, consequently improving impaired ovarian function in POI rats. This study provides robust evidence supporting moxibustion as a targeted intervention for treating POI by specifically regulating steroidogenesis in GCs.

Tuning Surface Organic Structures by Small Gas Molecules through Catassembly and Coassembly.

The field of molecular assembly has seen remarkable advancements across various domains, such as materials science, nanotechnology, and biomedicine. Small gas molecules serve as pivotal modulators, capable of altering the architecture of assemblies via tuning a spectrum of intermolecular forces including hydrogen bonding, dipole-dipole interactions, and metal coordination. Surface techniques, notably scanning tunneling microscopy and atomic force microscopy, have proven instrumental in dissecting the structural metamorphosis and characteristic features of these assemblies at an unparalleled single-molecule resolution. Recent research has spotlighted two innovative approaches for modulating surface molecular assemblies with the aid of small gas molecules: "catassembly" and "coassembly". This Perspective delves into these methodologies through the lens of varying molecular interaction types. The strategies discussed here for regulating molecular assembly structures using small gas molecules can aid in understanding various complex assembly processes and structures and provide guidance for the further fabrication of complex surface structures.

Robot-assisted minimally invasive bronchial resection with primary anastomosis for schwannoma arising from left main bronchus: a case report.

Background: Tracheobronchial schwannomas are extremely rare, which account for lower than 0.2% in all pulmonary tumors. In large part because of the rarity and insufficient reported clinical details, tracheobronchial schwannoma lacks guidelines or expert consensus for diagnosis and treatment, and the delay in diagnosis can range from months to years. The main treatment option is surgery. Endoscopic intervention can also be selected. An increasing number of thoracic surgery cases were performed on the robotic platforms in recent years. With their assistance, surgeons can accomplish the high technique required surgical procedures with ease. Case Description: In this case, a 48-year-old female had a history of shortness of breath for more than 1 year. The chest computed tomography (CT) and bronchoscopy examination revealed a new growth of nodule in the left main bronchus. The nodule was considered a schwannoma by transbronchial biopsy, which was removed by robot-assisted bronchial resection with primary anastomosis. The application of Da Vinci Si robotic surgical system benefited the process of this surgery. Pathology and immunohistochemistry results confirmed the diagnosis of schwannomas. The patient tolerated the treatment without any complications. No sign of recurrence was discovered at present, 6 months after the intervention. Conclusions: We reported the first sleeve resection for bronchial schwannoma using Da Vinci robotic surgical system. The clinical details of tracheobronchial schwannoma should be revealed more specifically to achieve more systematic diagnosis and treatment.

Observation of Chiral Channels in Helical Covalent Organic Frameworks.

Unraveling the mechanism of chirality transfer across length scales is crucial to the rational development of functional materials with hierarchical chirality. The key obstacle is the lack of structural information, especially at the mesoscopic level. We report herein the structural identification of helical covalent organic frameworks (heliCOFs) with hierarchical chirality, which integrate molecular chirality, channel chirality, and morphology chirality into one crystalline entity. Specifically, benefiting from the highly ordered structure of heliCOFs, the existence of chiral channels at the mesoscopic level has been confirmed by electron crystallography, and the handedness of these chiral channels has been directly determined through the stereopair imaging technique. Accordingly, the chirality transfer in heliCOFs from microscopic to macroscopic levels could be rationalized with a layer-rotating model that has been supported by both crystal structure analysis and theoretical calculations. Observation of chiral channels in heliCOFs not only provides unprecedented data for the understanding of the chirality transfer process but also sheds new light on the rational construction of highly ordered polymeric materials with hierarchical chirality.

[Essential oil of Cinnamomum camphora mitigates depression-like behavior in mice by regulating Nrf2/HO-1 pathway and inhibiting inflammatory cytokines].

This study aims to investigate the essential oil(EOL) of Cinnamomum camphora regarding its anti-depression effect and mechanism in regulating inflammatory cytokines and the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway. A mouse model of depression was established by intraperitoneal injection of lipopolysaccharide(LPS). Open field, elevated plus maze, and forced swimming tests were carried out to examine mouse behaviors. Western blot and qRT-PCR were employed to determine the expression of proteins and genes in the Nrf2/HO-1 pathway in the hippocampus. The levels of tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1ß in the serum were measured by enzyme-linked immunosorbent assay(ELISA). The changes of apoptosis in mouse brain were detected by Tunel staining. Compared with the blank control group, the model group showed shortened distance travelled and time spent in the central zone and reduced number of entries in the central zone in the open field test. In the elevated plus maze test, the model group showed reduced open arm time(OT%) and open arm entries(OE%). In the force swimming test, the model group showed extended duration of immobility compared with the blank control group. Compared with the model group, the treatment with EOL significantly increased the distance travelled and time spent in the central zone and increased the number of entries in the central zone in the open field test. In addition, EOL significantly increased the OT% and OE% in the elevated plus maze and shor-tened the immobility duration in the forced swimming test. The model group showed lower expression levels of Nrf2 and HO-1 and hig-her levels of TNF-α, IL-6, and IL-1ß than the blank control group. Compared with the model group, the treatment with EOL up-regulated the expression levels of Nrf2 and HO-1 and lowered the levels of TNF-α, IL-6, and IL-1ß. The Tunel staining results showed that the apoptosis rate in the brain tissue of mice decreased significantly after the treatment with EOL. To sum up, EOL can mitigate the depression-like behaviors of mice by up-regulating the expression of Nrf2 and HO-1 and preventing hippocampal inflammatory damage. The findings provide empirical support for the application of EOL and aromatherapy in the treatment of depression.

Differential Cantilever Enhanced Fiber-Optic Photoacoustic Sensor for Diffusion Gas Detection.

Aiming at the problem of the fiber-optic photoacoustic (PA) sensor being easily disturbed by external vibration and noise, a differential cantilever enhanced fiber-optic PA sensor is proposed for diffusion gas detection. The sensor comprises two PA tubes with the same structure and a pair of differential interferometric cantilevers. The two PA tubes are symmetrically distributed. The laser is incident on the PA tube as the signal channel to excite the PA pressure wave. Another tube without incident laser is used as the reference channel to suppress external disturbance. The external interference signals and PA signals superimposed with disturbance are detected by the differential cantilevers from the two channels. The signals are simultaneously restored by a single white-light interferometry demodulator, which multiplexed the spectral frequency domain of the superimposed interference spectrum. The experimental results show that the suppression effect of the differential cantilever enhanced PA sensor on ambient noise is improved by 80%, compared to the traditional single-cantilever sensor. The external cofrequency disturbance is suppressed by 20.9 dB. The minimum detection limit to acetylene (C2H2) downs to about 60 ppb with an integration time of 100 s. The sensor has excellent antivibration and electromagnetic interference ability.

Effect of external electric fields on the ESDPT process and photophysical properties of 1,8-dihydroxy-2-naphthaldehyde.

In this work, by capitalizing on the density functional theory (DFT) and the time-dependent density functional theory (TD-DFT) methods, it has been systematically studied that the excited state double intramolecular proton transfer (ESDPT) process and the photophysical properties of 1,8-dihydroxy-2-naphthaldehyde (DHNA) are affected by the distinct external electric fields (EEFs). The obtained intramolecular hydrogen bond (IHB) parameters containing bond lengths and angles, as well as infrared (IR) vibrational spectra demonstrate that IHB strength changes in the distinct EEFs. Moreover, not only do the potential energy surfaces (PESs) indicate that the ESDPT process of DHNA is stepwise, but also increasing the positive EEF results in a decrease in the energy barrier accordingly, while vice versa. The absorption and fluorescence spectra also undergo a corresponding red or blue shift in the EEF; for instance, when the EEF changes from +10 × 10-4 a.u. to +20 × 10-4 a.u., the fluorescence peak undergoes a blue shift from 602 nm to 513 nm in the keto2 form. In a nutshell, the ESDPT process of DHNA can be influenced by the EEF, which will serve as a reference in regulating and controlling proton transfer that causes luminescence.

Online tools to predict individualised survival for primary oesophageal cancer patients with and without pathological complete response after neoadjuvant therapy followed by oesophagectomy: development and external validation of two independent nomograms.

OBJECTIVE: This study aimed to develop and validate robust predictive models for patients with oesophageal cancer who achieved a pathological complete response (pCR) and those who did not (non-pCR) after neoadjuvant therapy and oesophagectomy. DESIGN: Clinicopathological data of 6517 primary oesophageal cancer patients who underwent neoadjuvant therapy and oesophagectomy were obtained from the National Cancer Database for the training cohort. An independent cohort of 444 Chinese patients served as the validation set. Two distinct multivariable Cox models of overall survival (OS) were constructed for pCR and non-pCR patients, respectively, and were presented using web-based dynamic nomograms (graphical representation of predicted OS based on the clinical characteristics that a patient could input into the website). The calibration plot, concordance index and decision curve analysis were employed to assess calibration, discrimination and clinical usefulness of the predictive models. RESULTS: In total, 13 and 15 variables were used to predict OS for pCR and non-pCR patients undergoing neoadjuvant therapy followed by oesophagectomy, respectively. Key predictors included demographic characteristics, pretreatment clinical stage, surgical approach, pathological information and postoperative treatments. The predictive models for pCR and non-pCR patients demonstrated good calibration and clinical utility, with acceptable discrimination that surpassed that of the current tumour, node, metastases staging system. CONCLUSIONS: The web-based dynamic nomograms for pCR (https://predict-survival.shinyapps.io/pCR-eso/) and non-pCR patients (https://predict-survival.shinyapps.io/non-pCR-eso/) developed in this study can facilitate the calculation of OS probability for individual patients undergoing neoadjuvant therapy and radical oesophagectomy, aiding clinicians and patients in making personalised treatment decisions.

Effect of marinating with green tea extract on the safety and sensory profiles of oven-baked oyster.

Baked oyster is a popular seafood dish around the world. The present study investigated the effect of various concentrations of a green-tea extract (GTE) marinade on the safety and sensory profiles of oysters baked for different durations. The results showed 10 g/L of GTE and 10-min baking time was the optimal combination, as supported by significantly attenuated lipid oxidation (35.29 %) and Nε-(carboxyethyl)lysine (CEL) content (48.51 %) without appreciable negative impact on the sensory or nutritional quality of the oysters. However, high concentrations of the marinade or prolonged baking promoted protein oxidation and Nε-(carboxymethyl)lysine (CML) formation likely through the pro-oxidative action of the GTE phytochemicals. Correlation analysis further revealed the main factors that affected CML, CEL, and fluorescent AGEs generation, respectively. These findings provide theoretical support for the protective effect and mechanism of GTE against quality deterioration of baked oysters and would help broaden the application of GTE in the food industry.

Insights into the influence of polystyrene microplastics on the bio-degradation behavior of tetrabromobisphenol A in soil.

Soil contamination by emerging pollutants tetrabromobisphenol A (TBBPA) and microplastics has become a global environmental issue in recent years. However, little is known about the effect of microplastics on degradation of TBBPA in soil, especially aged microplastics. In this study, the effect of aged polystyrene (PS) microplastics on the degradation of TBBPA in soil and the mechanisms were investigated. The results suggested that the aged microplastics exhibited a stronger inhibitory effect on the degradation of TBBPA in soil than the pristine microplastics, and the degradation efficiency of TBBPA decreased by 21.57% at the aged microplastic content of 1%. This might be related to the higher TBBPA adsorption capacity of aged microplastics compared to pristine microplastics. Aged microplastics strongly altered TBBPA-contaminated soil properties, reduced oxidoreductase activity and affected microbial community composition. The decrease in soil oxidoreductase activity and relative abundance of functional microorganisms (e.g., Bacillus, Pseudarthrobacter and Sphingomonas) caused by aged microplastics interfered with metabolic pathways of TBBPA. This study indicated the importance the risk assessment and soil remediation for TBBPA-contaminated soil with aged microplastics.

The mediating and moderating effects of resilience on the relationship between sleep quality and psychological distress in Chinese women with infertility.

BACKGROUND: Research has widely indicated that the psychological distress experienced by infertile patients during fertility treatments may have a negative effect on the results of assisted reproduction. Although numerous studies have shown that psychological resilience and sleep quality are important influencing factors for psychological distress, the mediating mechanisms of psychological resilience in the relationship between sleep quality and psychological distress for Chinese women in particular remain unclear. Therefore, the current study investigates the association between sleep quality, resilience, and psychological distress in Chinese women with infertility and examines the mediating and moderating roles of resilience on the relationship between sleep quality and psychological distress. METHODS: In this cross-sectional study, a total of 595 women with infertility who were undergoing IVF-ET were recruited at the Reproductive Medicine, Shandong University, from April to November 2019. Participants were instructed to complete four questionnaires, including a questionnaire about socio-demographic and clinical-related information, the Pittsburgh Sleep Quality Index (PSQI), the 10-item Connor-Davidson Resilience Scale (CD-RISC-10), and the Kessler-10 (K10). Pearson's correlation analysis was conducted preliminarily to describe the relationships between sleep quality, resilience, and psychological distress. A mediation model and a moderated model were constructed and analyzed using the PROCESS macro for SPSS. The Johnson-Neyman (J-N) technique was then used to identify the regions of significance across the levels of moderator values. RESULTS: Patients in the sample had a high prevalence of psychological distress (48.6%, K10 scores > 22), and mediation analysis indicated that resilience played a partially mediating role in the relationship between sleep quality and psychological distress (indict effect = 0.072, P < 0.001). Moderation analysis indicated that resilience also moderated the association between sleep quality and psychological distress. CONCLUSIONS: Resilience may play a key role in the relationship between sleep quality and psychological distress. Our findings imply that resilience training may therefore be an effective component of psychological distress intervention in women with infertility.

Multi-step strategies for synergistic treatment of urinary tract infections based on D-xylose-decorated antimicrobial peptide carbon dots.

Urinary tract infections (UTIs) caused by Uropathogenic Escherichia coli (UPEC), often reoccur due to the formation of intracellular bacterial colonies (IBCs) and antibiotic resistance. Given the significance of YadC for UPEC infection in our previous study, we developed D-xylose-decorated ɛ-poly-L-lysine (εPL)-based carbon dots (D-xyl@εPLCDs) that can be traced, and employed multi-step approaches to elucidate the functional roles of D-xyl@εPLCDs in UPEC infection. Compared to undecorated particles, D-xyl@εPLCDs demonstrate YadC-dependent bacterial targeting and exhibit enhanced bactericidal activities both intracellularly and extracellularly. Moreover, pre-treatment of D-xyl@εPLCDs before infection blocked the subsequent adhesion and invasion of UPEC to bladder epithelial cells 5637. Increase of ROS production and innate immune responses were observed in bladder epithelial cells 5637 treated with D-xyl@εPLCDs. In addition, treatment of D-xyl@εPLCDs post-infection facilitated clearance of UPEC in the bladders of the UTI mouse model, and reduced ultimate number of neutrophils, macrophages and inflammatory responses raised by invaded bacteria. Collectively, we presented a comprehensive evaluating system to show that D-xyl@εPLCDs exhibits superior bactericidal effects against UPEC, making them a promising candidate for drug development in clinical UTI therapeutics.

Ultrahigh-speed phase demodulation of a Fabry-Perot sensor based on fiber array parallel spectral detection.

An ultrahigh-speed phase demodulation system was designed for the Fabry-Perot (F-P) interferometric sensor based on fiber array parallel spectral detection. A high-power amplified spontaneous emission (ASE) source served as the broadband detection light. The spectrum generated by the dispersion of the F-P interference light through an arrayed waveguide grating (AWG) was incident into the fiber array and was detected in parallel by 48 photodiodes. The 48-channel signals were acquired synchronously and processed in real time to achieve a phase demodulation for the F-P cavity at 200 kHz. As a result, a low-resolution spectral detection and demodulation system was constructed with high speed. The length demodulation range of the F-P cavity was 60-700 µm, and the demodulation resolution was as high as 0.22 nm. The designed high-sensitivity demodulator is expected to be used for ultrasonic and high-frequency vibration detection.

A non-metal single atom nanozyme for cutting off the energy and reducing power of tumors.

Enzymes are considered safe and effective therapeutic tools for various diseases. With the increasing integration of biomedicine and nanotechnology, artificial nanozymes offer advanced controllability and functionality in medical design. However, several notable gaps, such as catalytic diversity, specificity and biosafety, still exist between nanozymes and their native counterparts. Here we report a non-metal single-selenium (Se)-atom nanozyme (SeSAE), which exhibits potent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mimetic activity. This novel single atom nanozyme provides a safe alternative to conventional metal-based catalysts and effectively cuts off the cellular energy and reduction equivalents through its distinctive catalytic function in tumors. In this study, we have demonstrated the substantial efficacy of SeSAE as an antitumor nanomedicine across diverse mouse models without discernible systemic adverse effects. The mechanism of the NADPH oxidase-like activity of the non-metal SeSAE was rationalized by density functional theory calculations. Furthermore, comprehensive elucidation of the biological functions, cell death pathways, and metabolic remodeling effects of the nanozyme was conducted, aiming to provide valuable insights into the development of single atom nanozymes with clinical translation potential.

High-Precision Multipass Fiber-Optic Photoacoustic Gas Analyzer Based on 2f/1f Wavelength Modulation Spectroscopy.

A self-calibration fiber-optic photoacoustic (PA) gas analyzer based on 2f/1f wavelength modulation spectroscopy (WMS) is proposed, which utilizes gas and solid multipass absorption enhancement. The laser light is incident obliquely on the cell wall, and one end of the cell is equipped with a highly reflective mirror. The gas analyzer takes full advantage of the miniature multipass PA cell, which enhances the absorption of gas and solid simultaneously. As a result, the double absorption enhancement of 1f and 2f PA signals are realized. A dual-channel lock-in white-light interferometer based on fiber-optic PA demodulation is designed to simultaneously extract the 1f and 2f PA signals detected by the silicon cantilever. The experimental results of methane gas detection show that the minimum detection limit (MDL) of the PA gas analyzer is 20 ppb when the integration time is 60 s. Moreover, the detection error of gas concentration is within 3% when the laser power is reduced by half. The fiber-optic PA gas analyzer eliminates the influence of changes in the laser power and optical path loss, which can be used for the high-precision detection of trace gases.

A domain-label-guided translation model for molecular optimization.

Molecular optimization, which aims to improve molecular properties by modifying complex molecular structures, is a crucial and challenging task in drug discovery. In recent years, translation models provide a promising way to transform low-property molecules to high-property molecules, which enables molecular optimization to achieve remarkable progress. However, most existing models require matched molecular pairs, which are prone to be limited by the datasets. Although some models do not require matched molecular pairs, their performance is usually sacrificed due to the lack of useful supervising information. To address this issue, a domain-label-guided translation model is proposed in this paper, namely DLTM. In the model, the domain label information of molecules is exploited as a control condition to obtain different embedding representations, enabling the model to generate diverse molecules. Besides, the model adopts a classifier network to identify the property categories of transformed molecules, guiding the model to generate molecules with desired properties. The performance of DLTM is verified on two optimization tasks, namely the quantitative estimation of drug-likeness and penalized logP. Experimental results show that the proposed DLTM is superior to the compared baseline models.

Immune microenvironment heterogeneity of concurrent adenocarcinoma and squamous cell carcinoma in multiple primary lung cancers.

The molecular profiles and tumor immune microenvironment (TIME) of multiple primary lung cancers (MPLCs) presenting as concurrent lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC) remain unknown. We aimed to clarify these factors. We performed whole-exome sequencing (WES), RNA sequencing (RNA-Seq), and multiplex immunohistochemistry (mIHC) for five patients with concurrent ADC and SQCC. We found the genetic mutations were similar between ADC and SQCC groups. RNA-Seq revealed that the gene expression and pathways enriched in ADC and SQCC groups were quite different. Gene set enrichment analysis (GSVA) showed that nine gene sets were significantly differentially expressed between the ADC and SQCC groups (p < 0.05), with four gene sets relevant to squamous cell features upregulated in the SQCC group and five gene sets upregulated in the ADC group. Reactome enrichment analysis of differentially expressed genes showed that the immune function-related pathways, including programmed cell death, innate immune system, interleukin-12 family signaling, and toll-like receptor 2/4 pathways, etc. were significantly enriched. Transcriptomic TIME analysis, with mIHC in patient specimens and in vivo validation, showed tumor-infiltrating immune cells were significantly more enriched and diverse in ADC, especially CD8 + T cells. Our results revealed that the transcriptomic profiles and TIME features were quite different between ADC and SQCC lesions. ADC lesions exhibited a more active TIME than SQCC lesions in MPLCs.