Optical feedback frequency locking: impact of directly reflected field and responding strategies.

The challenges presented by the directly reflected field in optical feedback cavity-enhanced spectroscopy systems serve as substantial obstacles, introducing additional complexity to existing systems and compromising their sensitivity, as the underlying mechanisms of its adverse effects remain not fully understood. This study aims to address this issue by introducing a comprehensive analytical model. Additionally, frequency locking can be achieved by decreasing the feedback rate, the laser's linewidth enhancement factor, and the directly reflected field, and by increasing the refractive index of the gain medium, the length of the laser's resonant cavity, the electric field reflectivity of the laser's output facet, and the resonant field. These parameters can affect the feedback coupling rate pre-factor, and for a resonant cavity with a length of 0.394 m, optical feedback can only be established when the feedback coupling rate pre-factor is less than 1.05 × 109. Through experimental validation, we successfully confirm the effectiveness of the proposed solution in eliminating the detrimental effects of the directly reflected field. Importantly, this suppression is achieved without compromising other aspects of the system's performance. The research findings not only offer the potential to optimize various cavity-enhanced spectroscopy systems that rely on optical feedback but also show promising applications in advancing the development of high-purity spectrum diode lasers utilizing optical feedback from an external high-finesse cavity.

Case report: Intraabdominal infection of Mycobacterium syngnathidarum in an immunocompetent patient confirmed by whole-genome sequencing.

Background: The taxonomic group of non-tuberculous mycobacteria (NTM) encompasses more than 190 species and subspecies, some of which can cause pulmonary and extrapulmonary diseases across various age groups in humans. However, different subspecies exhibit differential drug sensitivities, and traditional detection techniques struggle to accurately classify NTM. Therefore, clinicians need more effective detection methods to identify NTM subtypes, thus providing personalized medication for patients. Case presentation: We present the case of a 47-year-old female patient diagnosed with an intraabdominal infection caused by Mycobacterium syngnathidarum. Despite computed tomography of the chest suggesting potential tuberculosis, tuberculosis infection was ruled out due to negative TB-DNA results for ascites fluid and sputum and limited improvement of lung lesions after treatment. Additionally, acid-fast staining and Lowenstein-Jensen culture results revealed the presence of mycobacterium in ascites fluid. Subsequent whole-genome sequencing (WGS) confirmed the DNA sequences of Mycobacterium syngnathidarum in colonies isolated from the ascites fluid, which was further corroborated by polymerase chain reaction and Sanger sequencing. Ultimately, the patient achieved a complete recovery following the treatment regimen targeting Mycobacterium syngnathidarum, which involved clarithromycin, ethambutol hydrochloride, pyrazinamide, rifampicin, and isoniazid. Conclusion: This is the first reported case of Mycobacterium syngnathidarum infection in humans. Mycobacterium syngnathidarum was detected by WGS in this case, suggesting that WGS may serve as a high-resolution assay for the diagnosis of different subtypes of mycobacterium infection.

Simple technique of coupling a diode laser into a linear power buildup cavity for Raman gas sensing.

We report a novel, to the best of our knowledge, and simple technique to lock a 642 nm multi-quantum well diode laser to an external linear power buildup cavity by directly feeding the cavity reflected light back to the diode laser for enhancement of gas Raman signals. The dominance of the resonant light field in the locking process is achieved by reducing the reflectivity of the cavity input mirror and thus making the intensity of the directly reflected light weaker than that of the resonant light. Compared with traditional techniques, stable power buildup in the fundamental transverse mode TEM00 is guaranteed without any additional optical elements or complex optical arrangements. An intracavity exciting light of 160 W is generated with a 40 mW diode laser. Using a backward Raman light collection geometry, detection limits at the ppm level are achieved for ambient gases (N2, O2) with an exposure time of 60 s.

Lumican and tumor therapy resistance / 国际肿瘤学杂志

Lumican is a member of the small leucine-rich proteoglycan family, which is involved in cell processes related to tumorigenesis and development, such as epithelial-mesenchymal transition, cell proliferation, migration, invasion and adhesion. The expression of Lumican in different tumors is positively or negatively correlated with tumor progression, and can be used as a reference for tumor prognosis and efficacy evaluation. Further study of the correlation and potential mechanism between Lumican and tumor therapy resistance can provide new ideas for predicting clinical therapeutic efficacy.

CT-Based Weighted Radiomic Score Predicts Tumor Response to Immunotherapy in Non-Small Cell Lung Cancer / 中国医学科学院学报

Objective To develop a CT-based weighted radiomic model that predicts tumor response to programmed death-1(PD-1)/PD-ligand 1(PD-L1)immunotherapy in patients with non-small cell lung cancer.Methods The patients with non-small cell lung cancer treated by PD-1/PD-L1 immune checkpoint inhibitors in the Peking Union Medical College Hospital from June 2015 to February 2022 were retrospectively studied and classified as responders(partial or complete response)and non-responders(stable or progressive disease).Original radiomic features were extracted from multiple intrapulmonary lesions in the contrast-enhanced CT scans of the arterial phase,and then weighted and summed by an attention-based multiple instances learning algorithm.Logistic regression was employed to build a weighted radiomic scoring model and the radiomic score was then calculated.The area under the receiver operating characteristic curve(AUC)was used to compare the weighted radiomic scoring model,PD-L1 model,clinical model,weighted radiomic scoring + PD-L1 model,and comprehensive prediction model.Results A total of 237 patients were included in the study and randomized into a training set(n=165)and a test set(n=72),with the mean ages of(64±9)and(62±8)years,respectively.The AUC of the weighted radiomic scoring model reached 0.85 and 0.80 in the training set and test set,respectively,which was higher than that of the PD-L1-1 model(Z=37.30,P<0.001 and Z=5.69,P=0.017),PD-L1-50 model(Z=38.36,P<0.001 and Z=17.99,P<0.001),and clinical model(Z=11.40,P<0.001 and Z=5.76,P=0.016).The AUC of the weighted scoring model was not different from that of the weighted radiomic scoring + PD-L1 model and the comprehensive prediction model(both P>0.05).Conclusion The weighted radiomic scores based on pre-treatment enhanced CT images can predict tumor responses to immunotherapy in patients with non-small cell lung cancer.

Computer Vision in Medical Imaging and its Impact on the Rare Musculoskeletal Diseases / 罕见病研究

There are over 6000 rare diseases in the world, affecting more than 300 million people. Early and precise diagnosis of rare diseases has always been the goal in clinical medicine. Emerging computer vision technology now greatly enhance medicine and healthcare and shows the potential in assisting the diagnosis and treatment for rare diseases. The technology can be a useful tool for extracting disease-relevant patterns from medical imaging. However, the effectiveness of its application depends on the complexity of the medical cases. In this paper, we summarize the challenges and emerging solution for the application of computer vision in diagnosis, rehabilitation as well as management of rare musculoskeletal diseases.

Comprehensive folding variations for protein folding.

The revelation of protein folding is a challenging subject in both discovery and description. Except for acquirement of accurate 3D structure in protein stable state, another big hurdle is how to discover structural flexibility for protein innate character. Even if a huge number of flexible conformations are known, difficulty is how to represent these conformations. A novel approach, protein structure fingerprint, has been developed to expose the comprehensive local folding variations, and then construct folding conformations for entire protein. The backbone of five amino acid residues was identified as a universal folden, and then a set of Protein Folding Shape Code (PFSC) was derived for completely covering folding space in alphabetic description. Sequentially, a database was created to collect all possible folding shapes of local folding variations for all permutation of five amino acids. Successively, Protein Folding Variation Matrix (PFVM) assembled all possible local folding variations along sequence for a protein, which possesses several prominent features. First, it showed the fluctuation with certain folding patterns along sequence which revealed how the protein folding was related the order of amino acids in sequence. Second, all folding variations for an entire protein can be simultaneously apprehended at a glance within PFVM. Third, all conformations can be determined by local folding variations from PFVM, so total number of conformations is no longer ambiguous for any protein. Finally, the most possible folding conformation and its 3D structure can be acquired according PFVM for protein structure prediction. Therefore, the protein structure fingerprint approach provides a significant means for investigation of protein folding problem.

Free energy change estimation: The Divide and Conquer MBAR method.

In the present study, the Divide and Conquer MBAR (DC-MBAR) method is proposed to predict the free energies based on the data sampled by multi-states simulations. For DC-MBAR method, the overlap between any two alchemical states is calculated first and those with sufficient overlap are defined as the adjacent states. Unlike the traditional MBAR method, which calculates the free energy of each state using all the data at once, DC-MBAR focuses on predicting the free energy changes between adjacent states. To estimate the free energy changes accurately, the other states with overlaps with the two adjacent states bigger than the defined threshold are included in the MBAR equation. At a specific threshold, the free energies predicted by DC-MBAR are very close to those calculated by the traditional MABR method. Furthermore, DC-MBAR scheme can reduce both the computation and memory cost. One important characteristic of DC-MBAR method is linear scaling, which means the CPU time with the change of the number of states is a straight-line relation. As the pair-based calculations are mutually independent and parallelizable, all accessible CPU cores on the HPC cluster could be utilized, which makes DC-MBAR strategy more efficient.

Value of CD4/CD8 ratio and total B lymphocytes before radiotherapy in predicting radiation pneumonitis in patients with esophageal cancer and lung cancer / 国际肿瘤学杂志

Objective:To investigate the value of CD4/CD8 ratio and total B lymphocytes before radiotherapy in predicting the occurrence of radiation pneumonitis (RP) in patients with esophageal cancer and lung cancer.Methods:The clinicopathological data of 28 patients with esophageal and 16 patients with lung cancer undergoing radiotherapy from April 2018 to March 2020 in Hefei Cancer Hospital, Chinese Academy of Sciences were retrospectively analyzed, and the patients were divided into RP group ( n=16) and non-RP group ( n=28) according to whether RP occurred during and after treatment. The CD4/CD8 ratio and total B lymphocytes before radiotherapy between the two groups, and the CD4/CD8 ratio and total B lymphocytes before and after radiotherapy in the RP group were compared. Receiver operating characteristic curve was used to analyze the value of CD4/CD8 ratio and total B lymphocytes before radiotherapy in predicting RP. Results:The CD4/CD8 ratio before radiotherapy in the RP group was significantly lower than that in the non-RP group (0.993±0.179 vs. 1.708±0.170), with a statistically significant difference ( t=2.706, P=0.009); the total B lymphocytes in the RP group was significantly lower than that in non-RP group [(4.409±0.823)% vs. (8.153±1.017)%], with a statistically significant difference ( t=0.986, P=0.015). The CD4/CD8 ratio in the RP group was lower than that before radiotherapy when RP occurred (0.785±0.167 vs. 0.993±0.179), with no statistically significant difference ( t=1.376, P=0.189). The total B lymphocytes in the RP group was lower than that before radiotherapy when RP occurred [(3.487±1.018)% vs. (4.409±0.823)%], with no statistically significant difference ( t=0.804, P=0.433). The critical values of CD4/CD8 ratio and total B lymphocytes predicted RP were 0.580 and 0.357, respectively. The areas under the curve (AUC) of CD4/CD8 for predicting RP was 0.802 (95% CI: 0.653-0.932), the sensitivity was 89.29%, and the specificity was 68.75%. The AUC of total B lymphocytes for predicting RP was 0.694 (95% CI: 0.483-0.814), the sensitivity was 85.71%, and the specificity was 50.00%. The AUC of the two combined diagnostic method for RP was 0.834 (95% CI: 0.697-0.932), the sensitivity and specificity were 81.25% and 89.29%. AUC of the two combined tests was significantly higher than that of the single test, with statistically significant differences ( Z=1.115, P=0.046; Z=1.992, P=0.026). Conclusion:The CD4/CD8 ratio and total B lymphocytes in the RP group are lower than those in the non-RP group. The CD4/CD8 ratio and total B lymphocytes in the serum are of great significance in predicting the occurrence of RP in patients with malignant tumors receiving chest radiotherapy.

PBX1 is a valuable prognostic biomarker for patients with breast cancer.

Pre-B-cell leukemia transcription factor (PBX) proteins have important roles in the development of numerous organs. To date, four members of the PBX family have been identified to be involved in human cancer but little is known about their expression patterns and precise functions in breast cancer (BC) progression. The aim of the present study was to determine whether they have the potential to be prognostic biomarkers in patients with BC. The expression patterns of PBXs were evaluated using Oncomine, Cancer Cell Line Encyclopedia and Gene expression-based Outcome for Breast cancer Online algorithm analyses. The prognostic value of PBX1 was determined by Kaplan-Meier plotter analysis. It was observed that, among all PBX family members, only PBX1 was significantly upregulated in BC vs. normal tissues. Meta-analysis in the Oncomine database revealed that PBX1 was significantly upregulated in invasive breast carcinoma stroma, ductal breast carcinoma, invasive lobular breast carcinoma, invasive mixed breast carcinoma and male breast carcinoma compared with normal tissues. In addition, PBX1 was significantly correlated with forkhead box protein A1. Subtype analysis indicated that PBX1 overexpression was associated with luminal-like and hormone receptor-sensitive subtypes. In the survival analysis, a high expression level of PBX1 was associated with poor prognosis of patients with estrogen receptor (ER)-positive, luminal A and luminal B subtypes of BC. The results of the present study indicate that PBX1 may serve as a specific biomarker and essential prognostic factor for ER-positive, luminal A and luminal B subtypes of BC.

Relationship between tuberculosis and microbiota / 中华实用儿科临床杂志

Tuberculosis(TB) caused by the Mycobacterium tuberculosis(Mtb) is a worldwide public health threat.Microbiota in body affects human health and is involved in human diseases, and its clinical importance is begi-nning to be understood.In this review, studies on the relationship between the establishment of Mtb infection and microbiota as well as the development and antibiotic treatment of Mtb infection were discussed.Studies have shown that: (1) microbiota influences the establishment of Mtb infection; (2) co-infection of Helicobacter pylori alters susceptibility to Mtb infection and progression of active TB; (3) microbiota influences the progression of TB by regulating the nutritio-nal, metabolic and immune status of the host; (4) susceptibility to reinfection increases in TB patients treated with antibiotics, possibly due to T-cell epitope depletion of common intestinal non-Mtb Mycobacterium, the effects of antibio-tics are long-term in patients; (5) the occurrence of childhood TB is age-related and many factors such as co-infection and vaccine inoculation increase risk.An in-depth study of the relationship between the microbiota and TB will provide a new perspective on the prevention of TB.

Development of novel self-adhesive resin cement with antibacterial and self-healing properties / 华西口腔医学杂志

OBJECTIVE@#This study aimed to develop novel self-adhesive resin cement with antibacterial and self-healing properties. Furthermore, the dentin bonding strength, mechanical properties, self-healing efficiency, and antibacterial property of the developed cement were measured.@*METHODS@#Novel nano-antibacterial inorganic fillers that contain quaternary ammonium salts with long-chain alkyls were synthesized. These fillers were added into self-adhesive resin cement containing self-healing microcapsules at mass fractions of 0, 2.5%, 5.0%, 7.5%, or 10.0%. The dentin shear bonding test was used to test the bonding strength, whereas the flexural test was used to measure the flexural strength and elastic modulus of the cement. The single-edge V-notched beam method was used to measure self-healing efficiency, and human dental plaque microcosm biofilms were chosen to calculate the antibacterial property.@*RESULTS@#The dentin shear bond strength significantly decreased when the mass fraction of the nano-antibacterial inorganic fillers in the novel cement reached 7.5% (P0.1). Resin cement containing 2.5% mass fraction or more nano-antibacterial inorganic fillers significantly inhibited the metabolic activity of dental plaque microcosm biofilms, indicating strong antibacterial potency (P<0.05).@*CONCLUSIONS@#The novel self-adhesive resin cement exhibited promising antibacterial and self-healing properties, which enable the cement to be used for dental applications.

FOXK transcription factors: Regulation and critical role in cancer.

Growing evidence suggests that alterations of gene expression including expression and activities of transcription factors are closely associated with carcinogenesis. Forkhead Box Class K (FOXK) proteins, FOXK1 and FOXK2, are a family of evolutionarily conserved transcriptional factors, which have recently been recognized as key transcriptional regulators involved in many types of cancer. Members of the FOXK family mediate a wide spectrum of biological processes, including cell proliferation, differentiation, apoptosis, autophagy, cell cycle progression, DNA damage and tumorigenesis. Therefore, the deregulation of FOXKs can affect the cell fate and they promote tumorigenesis as well as cancer progression. The mechanisms of FOXKs regulation including post-translational modifications (PTMs), microRNAs (miRNAs) and protein-protein interactions are well demonstrated. However, the detailed mechanisms of FOXKs activation and deregulation in cancer progression are still inconclusive. In this review, we summarize the regulatory mechanisms of FOXKs expression and activity, and their role in the development and progression of cancer. We have discussed whether FOXKs act as tumor suppressors/oncoproteins in tumor cells and their therapeutic applications in malignant diseases are also discussed. This review may assist in designing experimental studies involving FOXKs and it would strength the therapeutic potential of FOXKs as targets for cancers.

Hyper-acidic fusion minipeptides escort the intrinsic antioxidative ability of the pattern recognition receptor CRP in non-animal organisms.

C-reactive protein (CRP) is widely used as a biomarker of inflammation. It plays important roles in innate immunity response as a member of pattern recognition receptors, by binding oxidation-specific epitopes including some intermediates of lipid oxidative chain reaction. The inferred antioxidative ability of CRP was ever demonstrated by only few in vitro evidences, and needs to be clarified especially in vivo. Herein, we expressed human CRP in three representative non-animal organisms (Escherichia coli, Saccharomyces cerevisiae, and tobacco) inherently lacking the milieu for CRP signalling, and found CRP did possess an intrinsic antioxidative ability. Heterologous CRP could confer increased oxidative resistance in its recombinant E. coli and yeast cells and transgenic tobaccos. We also revealed a positive correlation between the antioxidative effect of CRP and its solubility. Only soluble CRP could exhibit distinct antioxidative activity, while the CRP aggregates might be instead toxic (probably pro-oxidative) to cells. Moreover, fusion with hyper-acidic minipeptides could remarkably improve CRP solubility, and meanwhile guarantee or enhance CRP antioxidative ability. These results not only provide a new insight for understanding the etiology of CRP-involved inflammations and diseases, and also endorse a potential of CRP biotechnological applications in developing new pharmaceutical therapies and improving plant oxidative resistance.

CARK1 phosphorylates subfamily III members of ABA receptors.

Abscisic acid (ABA) plays a vital role in responses to abiotic stresses that allow plants to cope with environmental challenges. In this study, we analyzed ABA receptors of subfamily III as the potential targets of Cytosolic ABA Receptor Kinase 1 (CARK1). We previously found that CARK1 phosphorylated the subfamily III member RCAR11 at a distinct threonine residue (T78). Our study now shows the physical interaction of CARK1 with the receptors RCAR12/13/14 in vitro and in vivo. The catalytically inactive form CARK1-N204A did not interact with the receptors. Phosphorylation of these ABA receptors in vitro occurred at a serine/threonine amino acid residue corresponding to T78 in RCAR11, which is located in the loop of ß3 within a conserved site. Further analysis revealed that the phosphorylation of RCAR11T78 could increase the sensitivity of the pyr1pyl1pyl2pyl4 quadruple mutant (1124) to ABA, including the inhibition of root elongation and increasing drought tolerance. The analysis of CARK1:1124 complementation and the expression of ABA-related genes indicated that CARK1 could rescue the insensitivity of 1124 to ABA. Our results indicate that CARK1 tends to phosphorylate subfamily III ABA receptors, and the phosphosites RCAR11T78, RCAR12T105, RCAR13T101, and RCAR14S81 are the major sites involved in the activation of the ABA response pathway.

Triazoles bind the C-terminal domain of SMO: Illustration by docking and molecular dynamics simulations the binding between SMO and triazoles.

Itraconazole is an antagonist of the component Smoothened of Hedgehog pathway, which can inhibit the growth of medulloblastoma, basal cell carcinoma, and melanoma, etc. To research the binding mechanism of the Smoothened and triazoles, we used docking and molecular dynamics simulations on the Smoothened crystal structure and six triazoles. Unlike vismodegib, itraconazole can effectively bind into the pocket in the C-terminal domain of the Smoothened crystal structure instead of the N-terminal domain. The binding of itraconazole can change the conformation of the N-terminal domain even although itraconazole only had limited area contacting with N-terminal domain of the Smoothened. Besides, the binding of Itraconazole will not affect the binding of vismodegib. The strong binding affinity could be demonstrated between itraconazole and the Smoothened. Posaconazole and ketoconazole also had the strong binding affinity and the similar binding mode with the Smoothened crystal structure.

The Expression of CARK1 or RCAR11 Driven by Synthetic Promoters Increases Drought Tolerance in Arabidopsis thaliana.

Drought stress hinders plant growth and development, and abscisic acid (ABA) stimulates plants to respond to drought. Here, to increase plant tolerance to drought, we designed three synthetic promoters (Ap, Dp, ANDp) to determine transcription activity and drought stress resistance in plants resulting from combinations of (1) synthetic promoters and (2) the functional genes CARK1 (cytosolic ABA receptor kinase 1) and RCAR11 (regulatory components of ABA receptor 11). Transient expression of eGFP and the dual-luciferase assay demonstrated that the basal transcriptional activities of Ap and ANDp were present at low levels under normal conditions, while the synthetic promoters were apparently induced upon either treatment of exogenous ABA or co-transformation with effector DREB2A (dehydration-responsive element binding protein 2A). Analysis of the transgenic plants (Ap:CARK1, Dp:CARK1, ANDp:CARK1, and Dp:RCAR11-Ap:CARK1) showed that the synthetic promoters Ap, Dp, and ANDp increased the expression of exogenous genes in transgenic plants upon treatment of ABA or d-mannitol. ANDp:CARK1 and Dp:RCAR11-Ap:CARK1 transgenic plants were sensitive to ABA and d-mannitol during cotyledon greening and root growth. A drought tolerance assay revealed that ANDp:CARK1 and Dp:RCAR11-Ap:CARK1 exhibited a higher survival rate than others upon drought stress. These results indicate that the combinations ANDp:CARK1 and Dp:RCAR11-Ap:CARK1 can be used to generate drought stress resistance in plants.

PiViewer: An open-source tool for automated detection and display of π-π interactions.

π-π interactions are common and important noncovalent interactions that contribute to biochemical molecular interactions, but the tools for the convenient 3D visualization of π-π interactions are lacking. We have developed an open-source and easy-to-use tool for the automated identification and display of π-π stacking in 3D. It can percept the aromaticity of rings from any selected ligand and the surrounding residues, calculate the distances and dihedral angles between each pair of aromatic ring planes, as well as can highlight the various configurations of π-π interactions in 3D: the sandwich configuration, the T-shaped configuration, and the parallel-displaced configuration. In addition, the users can easily adjust or set their own criteria for π-π stacking.

[Antibacterial dental adhesive containing nanoantibacterial inorganic fillers].

OBJECTIVE: This investigation aimed to develop a novel antibacterial dental adhesive containing nanoantibacterial inorganic fillers and measure the dentin bonding strength, mechanical properties, and antibacterial property of the novel adhesive in vitro. METHODS: Novel nanoantibacterial inorganic fillers containing quaternary ammonium salt with long chain alkyl were synthesized on the basis of previous research. These novel nanoantibacterial inorganic fillers were added into the dental adhesive to prepare novel nanoantibacterial dental resin composite at mass fractions of 0%, 2.5%, 5.0%, 7.5%, and 10%; 0% was used as control. Dentin shear bonding test was used to evaluate the bonding strength. Flexural test was utilized to measure the novel resin composite flexural strength and elastic modulus. A dental plaque microcosm biofilm model with human saliva as inoculum was formed. Colony forming unit, lactic acid production, and live/dead assay of the biofilm on novel dental adhesive were calculated to assess the effect of novel dental adhesive on human dental plaque microcosm biofilm. RESULTS: The dentin shear bond strength, flexural strength, and elastic modulus were 28.9 MPa, 86.6 MPa, and 4.2 GPa, respectively, when the nanoantibacterial inorganic filler mass fraction in the dental adhesive reached approximately 5.0%. Consequently, the dentin shear bond strength and mechanical properties significantly increased. Addition of 2.5% nanoantibacterial inorganic fillers into the dental adhesive exerted no adverse effect on the mechanical properties significantly (P>0.05). Dental adhesive containing 5% or more nanoantibacterial inorganic fillers inhibited the metabolic activity of the dental plaque microcosm biofilm significantly, thereby displaying a strong antibacterial potency (P<0.05). CONCLUSIONS: This novel antibacterial dental adhesive, which contained 5.0% nanoantibacterial inorganic filler, exhibited promising bonding strength, mechanical property, and antibacterial ability. Hence, this adhesive can be potentially used in caries inhibition in dental application.