SARS-CoV-2 neutralising antibody therapies: Recent advances and future challenges.

The COVID-19 pandemic represents an unparalleled global public health crisis. Despite concerted research endeavours, the repertoire of effective treatment options remains limited. However, neutralising-antibody-based therapies hold promise across an array of practices, encompassing the prophylaxis and management of acute infectious diseases. Presently, numerous investigations into COVID-19-neutralising antibodies are underway around the world, with some studies reaching clinical application stages. The advent of COVID-19-neutralising antibodies signifies the dawn of an innovative and promising strategy for treatment against SARS-CoV-2 variants. Comprehensively, our objective is to amalgamate contemporary understanding concerning antibodies targeting various regions, including receptor-binding domain (RBD), non-RBD, host cell targets, and cross-neutralising antibodies. Furthermore, we critically examine the prevailing scientific literature supporting neutralising antibody-based interventions, and also delve into the functional evaluation of antibodies, with a particular focus on in vitro (vivo) assays. Lastly, we identify and consider several pertinent challenges inherent to the realm of COVID-19-neutralising antibody-based treatments, offering insights into potential future directions for research and development.

Regulating Crystallinity Mismatch Between Donor and Acceptor to Improve Exciton/Charge Transport in Efficient Organic Solar Cells.

Achieving a more balanced charge transport by morphological control is crucial in reducing bimolecular and trap-assisted recombination and enhancing the critical parameters for efficient organic solar cells (OSCs). Hence, a facile strategy is proposed to reduce the crystallinity difference between donor and acceptor by incorporating a novel multifunctional liquid crystal small molecule (LCSM) BDTPF4-C6 into the binary blend. BDTPF4-C6 is the first LCSM based on a tetrafluorobenzene unit and features a low liquid crystal phase transition temperature and strong self-assembly ability, conducive to regulating the active layer morphology. When BDTPF4-C6 is introduced as a guest molecule into the PM6 : Y6 binary, it exhibits better compatibility with the donor PM6 and primarily resides within the PM6 phase because of the similarity-intermiscibility principle. Moreover, systematic studies revealed that BDTPF4-C6 could be used as a seeding agent for PM6 to enhance its crystallinity, thereby forming a more balanced and favourable charge transport with suppressed charge recombination. Intriguingly, dual Förster resonance energy transfer was observed between the guest molecule and the host donor and acceptor, resulting in an improved current density. This study demonstrates a facile approach to balance the charge mobilities and offers new insights into boosting the efficiency of single-junction OSCs beyond 20 %.

The Successive Next Network as Augmented Regularization for Deformable Brain MR Image Registration.

Deep-learning-based registration methods can not only save time but also automatically extract deep features from images. In order to obtain better registration performance, many scholars use cascade networks to realize a coarse-to-fine registration progress. However, such cascade networks will increase network parameters by an n-times multiplication factor and entail long training and testing stages. In this paper, we only use a cascade network in the training stage. Unlike others, the role of the second network is to improve the registration performance of the first network and function as an augmented regularization term in the whole process. In the training stage, the mean squared error loss function between the dense deformation field (DDF) with which the second network has been trained and the zero field is added to constrain the learned DDF such that it tends to 0 at each position and to compel the first network to conceive of a better deformation field and improve the network's registration performance. In the testing stage, only the first network is used to estimate a better DDF; the second network is not used again. The advantages of this kind of design are reflected in two aspects: (1) it retains the good registration performance of the cascade network; (2) it retains the time efficiency of the single network in the testing stage. The experimental results show that the proposed method effectively improves the network's registration performance compared to other state-of-the-art methods.

Immunoassay and mass cytometry revealed immunological profiles induced by inactivated BBIBP COVID-19 vaccine.

With the global prevalence of COVID-19 and the constant emergence of viral variants, boosters for COVID-19 vaccines to enhance antibody titers in human bodies will become an inevitable trend. However, there is a lack of data on antibody levels and the protective effects of booster injections. This study monitored and analyzed the antibody potency and the antibody responses induced by the booster injection in the subjects who received three vaccine doses. The study was conducted in a multicenter collaboration and recruited 360 healthy adults aged 20-74. Participants received the first, second, and booster doses of inactivated Sinopharm/BBIBP COVID-19 vaccine at 0, 1, and 7 months. Vaccine-induced virus-specific antibody levels (SARS-COV-2-IgA/IgM/IgG) were monitored at multiple time points, surrogate virus neutralization test (sVNT), and the spatial distribution and proportion of immune cells and markers were analyzed using the CyTOF method before vaccination and a month after the second dose. The titers of SARS-CoV-2-IgA/IgM/IgG and neutralizing antibodies increased to a high level in the first month after receiving the second dose of vaccine and declined slowly after that. The antibody levels of SARS-CoV-2-IgG and sVNT were significantly increased at 0.5 months after the induction of the booster (p < 0.05). Despite a downward trend, the antibody levels were still high in the following 6 months. The B cell concentration (in humoral sample) a month after the second injection was significantly reduced compared to that before the vaccine injection (p < 0.05). The proportion of the C01 cell cluster was significantly decreased compared with that before vaccine injection (p < 0.05). Individual cell surface markers showed distinctions in spatial distribution but were not significantly different. This study has shown that serum antibody titer levels will decrease with time by monitoring and analyzing the antibody efficacy and the antibody reaction caused by the booster injection of healthy people who received the whole vaccination (completed three injections). Still, the significant peak of the antibody titer levels after booster highlights the recall immune response. It can maintain a high concentration of antibody levels for a long time, which signifies that the protection ability has been enhanced following the injection of booster immunization. Additionally, CyTOF data shows the active production of antibodies and the change in the immunity environment.

Detection of interstitial pneumonia with autoimmune features and idiopathic pulmonary fibrosis are enhanced by involvement of matrix metalloproteinases levels and clinical diagnosis.

BACKGROUND: Higher detection of interstitial pneumonia with autoimmune features (IPAF), and idiopathic pulmonary fibrosis (IPF), has significant diagnostic and therapeutic implications. Some matrix metalloproteinases (MMPs) have become reliable diagnostic biomarkers in IPAF and IPF in previous studies, yet relevant reliability remains to be recognized. MATERIALS AND METHODS: In this study, 36 ILDs patients, including 31 IPAF patients (Mean ± SD, 50.20 ± 5.10 years; 16 [51.6%] females) and five IPF patients (Mean ± SD, 61.20 ± 6.73 years; one [20.0%] females) were retrospectively enrolled. Serial serum samples were collected from patients with IPAF and IPF between January 2019 and December 2020. Notably, Serum MMPs levels were measured by U-PLEX Biomarker Group 1(Human) Multiplex Assays (MSD, USA). RESULTS: A combination of MMPs and combinatorial biomarkers was strongly associated with clinical subjects in this study (AUC, 0.597 for Stability vs. Improvement and 0.756 for Stability vs. Exacerbation). Importantly, the AUC of MMP-12 reaches 0.730 (p < 0.05, Stability AUC vs. Improvement AUC) while MMP-13 reaches 0.741 (p < 0.05, Stability AUC vs. Exacerbation AUC) showed better performance than other MMPs in two comparisons. CONCLUSIONS: Clinical risk factors and MMPs are strongly associated with either stratification of the disease of progression of IPAF or in two IPAF and IPF independent cohorts. To our knowledge, this is the first to illustrate that MMP-12 and MMP-13 may be expected to become typical promising biomarkers in Improvement - IPAF and Exacerbation - IPAF, respectively.

Improving solubility and oral bioavailability of a novel antimalarial prodrug: comparing spray-dried dispersions with self-emulsifying drug delivery systems.

To improve the solubility and oral bioavailability of a novel antimalarial agent ELQ-331(a prodrug of ELQ-300), spray-dried dispersions (SDD) and a self-emulsifying drug delivery system (SEDDS) were developed. SDD were prepared with polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) polymer carrier and Aeroperl® 300 Pharma and characterized by differential scanning calorimetry, powder X-ray diffraction. For SEDDS, solubility in oils, surfactants, and co-surfactants was determined and ternary phase diagram was constructed to show self-emulsifying area. SEDDS were characterized for spontaneous emulsification and droplet size distribution. The amorphous ELQ-331 SDD improved the solubility to 10× in fast-state simulated intestinal fluid and addition of sodium lauryl sulphate externally to SDDs further improved the solubility to ∼28.5× versus non-formulated drug. SEDDS had good self-emulsifying characteristics with small emulsion droplet sizes and narrow particle distribution. Oral pharmacokinetic studies for SDD and SEDDS formulations were performed in rats. The ELQ-331 rapidly converted to ELQ-300 soon after oral administration in rats. Exposure levels of ELQ-300 were about 1.4-fold higher (based on AUC) in SEDDS than SDD formulations. Poorly soluble drugs like ELQ-331 can be formulated using SDD or SEDDS to improve solubility and oral bioavailability.

Effect of N-acetylcysteine on exacerbations of bronchiectasis (BENE): a randomized controlled trial.

BACKGROUND: N-acetylcysteine is a classic mucolytic agent. This study aimed to investigate the efficacy of N-acetylcysteine on reducing the risk of exacerbations in bronchiectasis patients. METHODS: A prospective, randomized, controlled trial was conducted between April 1, 2014 and December 31, 2016 in five general hospitals in Shandong Province, China. Adult bronchiectasis patients with at least two exacerbations in the past year were potentially eligible. Patients were randomly assigned to receive oral N-acetylcysteine (600 mg, twice daily, 12 months) or on-demand treatment. RESULTS: A total of 161 patients were eligible for randomization (81 to the N-acetylcysteine group and 80 to the control group). During the 12-month follow-up, the incidence of exacerbations in the N-acetylcysteine group was significantly lower than that in the control group (1.31 vs. 1.98 exacerbations per patient-year; risk ratio, 0.41; 95% CI, 0.17-0.66; P = 0.0011). The median number of exacerbations in the N-acetylcysteine group was 1 (0.5-2), compared with 2 (1-2) in the control group (U = - 2.95, P = 0.003). A total of 24.7% of the N-acetylcysteine group patients and 11.3% of the control group patients remained exacerbation-free throughout the 12-month follow-up (χ2 = 4.924, P = 0.026). Compared with the control group, the volume of 24-h sputum in the N-acetylcysteine group was significantly reduced (t = - 3.091, P = 0.002). Additionally, the N-acetylcysteine group showed a significant improvement in the quality of life. No severe adverse events were reported in the intervention group. CONCLUSION: The long-term use of N-acetylcysteine is able to reduce the risk of exacerbations for bronchiectasis patients in Shandong Province, China. The results of this study should be verified in a larger randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02088216) (Registered date: March 5, 2014).

SR-2P vaginal microbicide gel provides protection against herpes simplex virus 2 when administered as a combined prophylactic and postexposure therapeutic.

Previously, we demonstrated that a single prophylactic dose of SR-2P, a novel dual-component microbicide gel comprising acyclovir and tenofovir, led to a modest increase in mouse survival following a lethal challenge of herpes simplex virus 2 (HSV-2). Here, we show that a dose of SR-2P administered 24 h prior to infection provides some protection against the virus, but to a lesser degree than SR-2P administered either once a day for 2 days or 1 h prior to infection. None of the prophylactic doses blocked infection by the virus, and all resulted in 80 to 100% lethality. However, given that a prophylactic dose still provided a significant reduction in overall clinical score, reduced rate of body weight loss, and increased median survival of the mice, we examined whether a repetitive dose regimen (postinfection) in addition to the prophylactic dose could prevent death and reduce the levels of virus in mice. Nearly all (9 of 10 in each group) of the mice that received SR-2P for 2 days prior to infection or that received SR-2P 1 h prior to infection and were administered SR-2P once a day for 10 days after infection showed no clinical symptoms of infection and no viral loads in vaginal swabs and survived for 28 days postinfection. Conversely, mice receiving no treatment or an identical vehicle treatment demonstrated advanced clinical signs and did not survive past day 9 postinfection. We conclude that SR-2P is an effective anti-HSV-2 agent in mice.

Chemical constituents from branch of Fraxinus sieboldiana.

Using a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, macroporous adsorbent resin, and reversed-phase HPLC, 115 compounds including diterpenes, sesquiterpenes, treterpenes, coumarins, lignans, fatty acid derivatives, and simple aromatic derivatives were isolated from an ethanol extract of branch of Fraxinus sieboldiana (Oleaceaue), and their structures of the compounds were elucidated by spectroscopic methods including 1 D, 2D NMR and MS techniques. Among them, 41 compounds were new. In previous reports, we have been described the isolation, structure elucidation, and bioactivities of the 41 new compounds and 22 known orii including 8 coumarins, 4 phenolic and 12 phenylethanoidal glycosides. As a consequence, we herein reported the isolation and structure elucidation of the remaining 50 known compounds including 8- hydroxy-12-oxoabieta-9(11),13-dien-20-oic 8, 20-lactone(1), 6beta-hydroxyfcrruginol(2),(+)-pisiferic acid(3), (+)-pisiferal(4),(+)-7-dehydroabiet6none(5), 1-oxomiltirone(6), subdigitatone(7), linarionoside B(8), (9S)-linarionoside B(9), (3R,9R)-3-hydroxy-7,8-dihydro-beta-ionol 9-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside(10), ursolic acid(11), betulinic acid(12), euscaphic acid(13), (+)-syringaresinol(14), (+)-fraxiresinol(15), (+)-1-hydroxysyringaresinol(16), pinoresinol(17), medioresinol(18), 8-acetoxypinoresinol(19), epipinoresinol(20), (-)-olivil(21), (+)-cyclo-olivil(22), 3,3'-dimethoxy-4,4',9-trihydroxy-7,9'-epoxylignan-7'-one(23),(+)-1-hydroxypinoresinol 4'-O-beta-D-glucopyranoside (24), (+)-1-hydroxypinoresinol 4"-O-beta-D-glucopyranoside(25),(+)-syringaresinol O-beta-D-glucopyranoside (26), liriodendrin (27), ehletianol D(28), icariside E5(29) (-)-(7R, 8R)-threo-1-C-syringylglycerol(30),(-)-(7R, 8S)-erythro-guaiacylglycerol (31),(-)-(7R, 8R)-threo-guaiacylglycerol(32), 3-(4-beta-D-glucopyranosyloxy-3-methoxy)-phenyl-2E-propenol(33),2,3-dihydroxy-l-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(34), 2,3-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-1-propanone (35), 3-hydroxy-l-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(36), omega-hydroxypropioguaiacone(37), sinapyladehyde(38), trans-p-hydroxycinnamaldehyde(39), syringic acid(40), vanilic acid(41), vanillin(42), 4-hydroxy-benzaldehyde (43), (24R)-24-ethyl-5alpha-cholestane-3beta,5,6beta-triol(44), beta-sitosterol(45), daucosterol(46), 2,6-dimethoxy-I,4-benzoquinone(47), 2,6-dimethoxy-pyran-4-one(48), 1-(beta-D-ribofuranosyl)uracil(49), and mannitol(50). Compouds 1-7,12,18,28-37,44 and 48 were obtained from the genus Fraxinus for the first time.

[Effects of antibiotics plus efflux pump inhibitors on mutant selection window of Pseudomonas aeruginosa in vitro].

OBJECTIVE: To explore the effects of antibiotics plus efflux pump (EPI) inhibitors on mutant selection window of Pseudomonas aeruginosa in vitro. METHODS: In standard strains, the minimum inhibitory concentrations (MICs) of meropenem, ceftazidime, amikacin and ciprofloxacin alone were measured. Then the MICs of four antibiotics respectively plus EPI, including reserpine, omeprazole, azithromycin, carbonyl cyanide m-chlorophenyl- hydrazone (CCCP) and Phe-Arg-ß-naphtylamide (PAßN), were measured by checkerboard test. And the mutant prevention concentrations (MPC) of antibiotics alone and antibiotics plus different EPIs were also measured by agar dilution method. Selection indices (SI) were acquired through MPC divided by MIC. Similarly, the SI of meropenem, ceftazidime and ciprofloxacin which respectively plus amikacin and amikacin plus ciprofloxacin were measured. In clinical strains, MIC, MPC and SI of antibiotics alone and four antibiotics plus CCCP were measured. RESULTS: In standard strains, the SI of meropenem, ceftazidime, amikacin and ciprofloxacin alone were >32, >32, 16 and 16. After adding EPI, the SI of four antibiotics were 16, 16, 16, 8 (reserpine), 16, 32, 16, 8 (omeprazole), 8, 16, 16, 8 (azithromycin), 8, 8, 16, 8 (CCCP) and 8, 16, 16, 8 (PAßN). The SI of meropenem, ceftazidime and ciprofloxacin plus amikacin were 4, 4, 8. And the SI of amikacin plus ciprofloxacin was 4. In clinical strains, the SI of ciprofloxacin significantly decreased after adding CCCP. CONCLUSIONS: Both MIC and MPC of meropenem, ceftazidime and ciprofloxacin decreased significantly after adding EPI. The mutant selection window decreased when ciprofloxacin was combined with CCCP.

The inhibitory effect of apatinib on different small cell lung cancer cells and in lung cancer-bearing mice and patients.

PURPOSE: To observe the inhibitory effect of the small molecule tyrosine kinase inhibitor apatinib on small cell lung cancer in vitro and vivo. MATERIAL AND METHODS: Three small lung cancer cells were selected CCK-8 and monoclonal assay was used to determine the effect of apatinib on proliferation. The effects on cell cycle and apoptosis were detected by flow cytometry and TUNEL. We observed the inhibitory effect of different doses of apatinib on xenograft tumor. The efficacy and safety of apatinib in 20 patients with advanced small cell lung cancer were observed. RESULTS: For small cell lung cancer with high expression of VEGFR2, apatinib has a significant inhibitory effect both in vitro and in vivo. It can play an inhibitory role by promoting apoptosis and cell cycle arrest pathways. For small cell lung cancer with low expression of VEGFR, the inhibitory effect on cells in vitro was not significant. It has certain inhibitory effect on nude mouse transplanted tumor and small cell lung cancer patients, but the effect is weaker than that of animal models and patients with small cell lung cancer cells with high expression of VEGFR2. CONCLUSION: Apatinib has a significant inhibitory effect on small cell lung cancer with high expression of VEGFR2 and may be a treatment for small cell lung cancer patients.

Decoding acute myocarditis in patients with COVID-19: Early detection through machine learning and hematological indices.

During the persistent COVID-19 pandemic, the swift progression of acute myocarditis has emerged as a profound concern due to its augmented mortality, underscoring the urgency of prompt diagnosis. This study analyzed blood samples from 5,230 COVID-19 individuals, identifying key blood and myocardial markers that illuminate the relationship between COVID-19 severity and myocarditis. A predictive model, applying Bayesian and random forest methodologies, was constructed for myocarditis' early identification, unveiling a balanced gender distribution in myocarditis cases contrary to a male predominance in COVID-19 occurrences. Particularly, older men exhibited heightened vulnerability to severe COVID-19 strains. The analysis revealed myocarditis was notably prevalent in younger demographics, and two subvariants COVID-19 progression paths were identified, characterized by symptom intensity and specific blood indicators. The enhanced myocardial marker model displayed remarkable diagnostic accuracy, advocating its valuable application in future myocarditis detection and treatment strategies amidst the COVID-19 crisis.

Cytotoxic monacolin analogs from Monascus purpureus-fermented rice.

Two new monacolin analogs, monacolins O (1) and P (2), along with three known analogs, have been isolated from the ethanolic extract of Monascus purpureus-fermented rice. Their structures and absolute configurations were elucidated by spectroscopic methods, especially 2D NMR and CD spectral analyses as well as chemical method. Both 1 and 2 were tested against five tumor cell lines, and compound 1 exhibited selective cytotoxic activity against A2780 and A549 cell lines, with IC50 values of 3.7 and 8.0 µM, respectively.

MBUTransNet: multi-branch U-shaped network fusion transformer architecture for medical image segmentation.

PURPOSE: Recently, transformers have been adopted to computer vision applications and achieve great success in image segmentation. However by simply applying transformers to medical segmentation task it is hard to achieve much higher accuracy than by traditional U-shaped network structures, which are based on CNNs and has been extensively researched. On the other hand, CNN structure pays more attention to local information and ignores global information, which is very important for the medical image segmentation dataset with cell scattered background. This motivates us to explore the feasibility of using U-shape effective fusion transformer network architectures for medical image segmentation tasks. METHODS: In this paper, we propose a multibranch U-shaped structure fusion transformer network (MBUTransNet), which consists of two distinct branches. In branch 1, Coordinate attention transformer is designed to extract long-term dependency information through weight coordinates. In branch 2, small U-net blocks and multiscale feature fusion block are proposed to replace convolution blocks of each layer and fuse the feature maps from different layers, respectively. RESULTS: Our experiments demonstrate that the proposed MBUTransNet has achieved a 0.076 and 0.1269 improvement in DICE compared to the previous best method on MoNuSeg and Synapse multiorgan segmentation dataset, respectively, while the model parameters will be no significant increase. CONCLUSION: Without bells and whistles, MBUTransNet achieves better performance on medical image datasets, including medical cell segmentation and abdominal organs segmentation. Compared with transformer-based methods, our proposed model also obtains quite competitive parameters.

Characterization of Early Gonadal Differentiation and Induction of Sex Reversal in the Rock Bream Oplegnathus fasciatus.

Rock bream (Oplegnathus fasciatus) is a typical fish that has a unique multiple sex chromosome system (♀X1X1X2X2/♂X1X2Y). We examined the early gonadal development in rock bream via continuous histological observations of the gonads at 40-120 days post hatching (dph). The fish was identified as a typical gonochorist, and female gonads were found to differentiate earlier than male gonads. The ovarian cavity of the female was initially observed at 80 dph, whereas the efferent duct of the male was not observed until 100 dph. Immunofluorescence with the vasa-antibody revealed that germ cells were predominantly distributed around the ovarian cavity in females and on the edge of the gonad in males during the early stages of sex differentiation. Sex reversal was induced via the oral administration of letrozole (LTZ), 17α-methyltestosterone (MT), and 17ß-estradiol (E2), respectively, during the labile period of gonadal development. LTZ and MT induced 100% masculinization of genotype-females, whereas E2 induced only 50-60% feminization of genotype-males. Such findings suggest that the fish retained high sexual plasticity despite the existence of the neo-Y chromosome. MT and E2 had negative effect on fish growth, whereas LTZ did not exert such side effect. LTZ and MT could accelerate gonadal development in sex-reversed genotype-males, whereas E2 inhibited gonadal development in genotype-females of rock bream. These findings provide a basis for further research on the mechanisms of sex determination and differentiation in fishes with X1X2Y sex chromosome system and provide a sex reversal protocol for rock bream.

Research on property and burning behavior of flammable casing for underground coal gasification.

In this work, the comprehensive properties of flammable casing for underground coal gasification is systematically investigated, including flammable casing material physical, chemical and mechanical properties and full-size flammable casing mechanical properties and burning behavior. The flammable casing material consists of magnesium alloy matrix and rare earth particles, thermal conductivity and expansion property of which are weak. Results of high-temperature tensile test reveal that flammable casing material has good high temperature strength which declines by 30 % at 300 °C. Corrosion rate of flammable casing material is relatively high without extra protection. The full-size flammable casing possesses considerable mechanical property, thread property and high temperature collapse resistance. Burning of flammable casing is safe and stable. Burning rate of flammable casing material can be effectively controlled by water flow. Combustion product of flammable casing presents powder condition, which has no risk of blocking the gasification channel. To sum up, flammable casing is necessary to the realization of underground coal gasifying process, which plays the significant role of the development and application of underground coal gasification technology.

Novel nutritional indicator as predictors among subtypes of lung cancer in diagnosis.

Introduction: Lung cancer is a serious global health concern, and its subtypes are closely linked to lifestyle and dietary habits. Recent research has suggested that malnutrition, over-nutrition, electrolytes, and granulocytes have an effect on the development of cancer. This study investigated the impact of combining patient nutritional indicators, electrolytes, and granulocytes as comprehensive predictors for lung cancer treatment outcomes, and applied a machine learning algorithm to predict lung cancer. Methods: 6,336 blood samples were collected from lung cancer patients classified as lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), and small cell lung cancer (SCLC). 2,191 healthy individuals were used as controls to compare the differences in nutritional indicators, electrolytes and granulocytes among different subtypes of lung cancer, respectively. Results: Our results demonstrated significant differences between men and women in healthy people and NSCLC, but no significant difference between men and women in SCLC patients. The relationship between indicators is basically that the range of indicators for cancer patients is wider, including healthy population indicators. In the process of predicting lung cancer through nutritional indicators by machine learning, the AUC of the random forest model was as high as 93.5%, with a sensitivity of 75.9% and specificity of 96.5%. Discussion: This study supports the feasibility and accuracy of nutritional indicators in predicting lung cancer through the random forest model. The successful implementation of this novel prediction method could guide clinicians in providing both effective diagnostics and treatment of lung cancers.

Evolution of the newest diagnostic methods for COVID-19: a Chinese perspective. / ä¸­å›½è§†è§’ä¸‹çš„æ–°å† è‚ºç‚Žæœ€æ–°è¯Šæ–­æ–¹æ³•æ¼”è¿›.

Coronavirus disease 2019 (COVID-19) has continued to spread globally since late 2019, representing a formidable challenge to the world's healthcare systems, wreaking havoc, and spreading rapidly through human contact. With fever, fatigue, and a persistent dry cough being the hallmark symptoms, this disease threatened to destabilize the delicate balance of our global community. Rapid and accurate diagnosis of COVID-19 is a prerequisite for understanding the number of confirmed cases in the world or a region, and an important factor in epidemic assessment and the development of control measures. It also plays a crucial role in ensuring that patients receive the appropriate medical treatment, leading to optimal patient care. Reverse transcription-polymerase chain reaction (RT-PCR) technology is currently the most mature method for detecting viral nucleic acids, but it has many drawbacks. Meanwhile, a variety of COVID-19 detection methods, including molecular biological diagnostic, immunodiagnostic, imaging, and artificial intelligence methods have been developed and applied in clinical practice to meet diverse scenarios and needs. These methods can help clinicians diagnose and treat COVID-19 patients. This review describes the variety of such methods used in China, providing an important reference in the field of the clinical diagnosis of COVID-19.

Correlation between immune-related Tryptophan-Kynurenine pathway and severity of severe pneumonia and inflammation-related polyunsaturated fatty acids.

BACKGROUND: Immune dysfunction and oxidative stress caused by severe pneumonia can lead to multiple organ dysfunction and even death, causing a significant impact on health and the economy. Currently, great progress has been made in the diagnosis and treatment of this disease, but the mortality rate remains high (approximately 50%). Therefore, there is still potential for further exploration of the immune response mechanisms against severe pneumonia. OBJECTIVE: This study analyzed the difference in serum metabolic profiles between patients with severe pneumonia and health individuals through metabolomics, aiming to uncover the correlation between the Tryptophan-Kynurenine pathway and the severity of severe pneumonia, as well as N-3/N-6 polyunsaturated fatty acids (PUFAs). METHODS: In this study, 44 patients with severe pneumonia and 37 health controls were selected. According to the changes in the disease symptoms within the 7 days of admission, the patients were divided into aggravation (n = 22) and remission (n = 22) groups. Targeted metabolomics techniques were performed to quantify serum metabolites and analyze changes between groups. RESULTS: Metabolomics analysis showed that serum kynurenine and kynurenine/tryptophan (K/T) were significantly increased and tryptophan was significantly decreased in patients with severe pneumonia; HETE and HEPE in lipids increased significantly, while eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), α-linolenic acid (linolenic acid, α-LNA), arachidonic acid (ARA), Dihomo-γ-linolenic acid (DGLA), and 13(s)-hydroperoxylinoleic acid (HPODE) decreased significantly. Additionally, the longitudinal comparison revealed that Linolenic acid, DPA, and Tryptophan increased significantly in the remission group, while and kynurenine and K/T decreased significantly. In the aggravation group, Kynurenine and K/T increased significantly, while ARA, 8(S)-hydroxyeicosatetraenoic acid (HETE), 11(S)-HETE, and Tryptophan decreased significantly. The correlation analysis matrix demonstrated that Tryptophan was positively correlated with DGLA, 12(S)-hydroxyeicosapentaenoic acid (HEPE), ARA, EPA, α-LNA, DHA, and DPA. Kynurenine was positively correlated with 8(S)-HETE and negatively correlated with DHA. Additionally, K/T was negatively correlated with DGLA, ARA, EPA, α-LNA, DHA, and DPA. CONCLUSION: This study revealed that during severe pneumonia, the Tryptophan-Kynurenine pathway was activated and was positively correlated with the disease progression. On the other hand, the activation of the Tryptophan-Kynurenine pathway was negatively correlated with N-3/N-6 PUFAs.

Review of therapeutic mechanisms and applications based on SARS-CoV-2 neutralizing antibodies.

COVID-19 pandemic is a global public health emergency. Despite extensive research, there are still few effective treatment options available today. Neutralizing-antibody-based treatments offer a broad range of applications, including the prevention and treatment of acute infectious diseases. Hundreds of SARS-CoV-2 neutralizing antibody studies are currently underway around the world, with some already in clinical applications. The development of SARS-CoV-2 neutralizing antibody opens up a new therapeutic option for COVID-19. We intend to review our current knowledge about antibodies targeting various regions (i.e., RBD regions, non-RBD regions, host cell targets, and cross-neutralizing antibodies), as well as the current scientific evidence for neutralizing-antibody-based treatments based on convalescent plasma therapy, intravenous immunoglobulin, monoclonal antibodies, and recombinant drugs. The functional evaluation of antibodies (i.e., in vitro or in vivo assays) is also discussed. Finally, some current issues in the field of neutralizing-antibody-based therapies are highlighted.