Correlation between small-cell lung cancer serum protein/peptides determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and chemotherapy efficacy.

BACKGROUND: Currently, no effective measures are available to predict the curative efficacy of small-cell lung cancer (SCLC) chemotherapy. We expect to develop a method for effectively predicting the SCLC chemotherapy efficacy and prognosis in clinical practice in order to offer more pertinent therapeutic protocols for individual patients. METHODS: We adopted matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and ClinPro Tools system to detect serum samples from 154 SCLC patients with different curative efficacy of standard chemotherapy and analyze the different peptides/proteins of SCLC patients to discover predictive tumor markers related to chemotherapy efficacy. Ten peptide/protein peaks were significantly different in the two groups. RESULTS: A genetic algorithm model consisting of four peptides/proteins was developed from the training group to separate patients with different chemotherapy efficacies. Among them, three peptides/proteins (m/z 3323.35, 6649.03 and 6451.08) showed high expression in the disease progression group, whereas the peptide/protein at m/z 4283.18 was highly expressed in the disease response group. The classifier exhibited an accuracy of 91.4% (53/58) in the validation group. The survival analysis showed that the median progression-free survival (PFS) of 30 SCLC patients in disease response group was 9.0 months; in 28 cases in disease progression group, the median PFS was 3.0 months, a statistically significant difference (χ2 = 46.98, P < 0.001). The median overall survival (OS) of the two groups was 13.0 months and 7.0 months, a statistically significant difference (χ2 = 40.64, P < 0.001). CONCLUSIONS: These peptides/proteins may be used as potential biological markers for prediction of the curative efficacy and prognosis for SCLC patients treated with standard regimen chemotherapy.

Analysis of hepatitis B virus infection in 1424 patients with different pathological types of lymphoma (2018-2022): A real-world, retrospective study.

OBJECTIVE: Recent studies have found a high prevalence of hepatitis B virus (HBV) infection in patients with non-Hodgkin's lymphoma (NHL), especially B-cell non-Hodgkin's lymphoma (B-NHL). However, most studies did not classify it and analyze the correlation between HBV and its various subtypes. METHODS: The authors retrospectively analyzed 1424 patients with lymphoma. Differences in the prevalence of HBV infection in patients with different pathological types of lymphoma were analyzed. The clinical characteristics, progression-free survival (PFS), and overall survival (OS) of HBV-positive and negative B-NHL subtypes were compared according to HBV infection. RESULTS: The HBV infection rate in NHL patients was 7.65%, which was higher than that in HL patients (2.59%, p < 0.05). The HBV infection rate in the B-NHL was higher than that in the T-cell non-Hodgkin's lymphoma (T-NHL) (8.14% vs. 4.95%). The HBV infection rate in the aggressive B-NHL was similar to that of the indolent B-NHL (8.30% vs. 7.88%), and the highest HBV infection rates were found in diffuse large B-cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, but no significant differences in clinical characteristics, PFS, and OS were seen between HBV-positive and negative patients in the two subtypes. CONCLUSIONS: There was an association between HBV infection and the development of NHL and HBV infection may play a role in the pathogenesis of B-NHL, but not T-NHL.

Shenqi Fuzheng injection alleviates chemotherapy-induced cachexia by restoring glucocorticoid signaling in hypothalamus.

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Renal interstitial fibrotic assessment using non-Gaussian diffusion kurtosis imaging in a rat model of hyperuricemia.

BACKGROUND: To investigate the feasibility of Diffusion Kurtosis Imaging (DKI) in assessing renal interstitial fibrosis induced by hyperuricemia. METHODS: A hyperuricemia rat model was established, and the rats were randomly split into the hyperuricemia (HUA), allopurinol (AP), and AP + empagliflozin (AP + EM) groups (n = 19 per group). Also, the normal rats were selected as controls (CON, n = 19). DKI was performed before treatment (baseline) and on days 1, 3, 5, 7, and 9 days after treatment. The DKI indicators, including mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) of the cortex (CO), outer stripe of the outer medulla (OS), and inner stripe of the outer medulla (IS) were acquired. Additionally, hematoxylin and eosin (H&E) staining, Masson trichrome staining, and nuclear factor kappa B (NF-κB) immunostaining were used to reveal renal histopathological changes at baseline, 1, 5, and 9 days after treatment. RESULTS: The HUA, AP, and AP + EM group MKOS and MKIS values gradually increased during this study. The HUA group exhibited the highest MK value in outer medulla. Except for the CON group, all the groups showed a decreasing trend in the FA and MD values of outer medulla. The HUA group exhibited the lowest FA and MD values. The MKOS and MKIS values were positively correlated with Masson's trichrome staining results (r = 0.687, P < 0.001 and r = 0.604, P = 0.001, respectively). The MDOS and FAIS were negatively correlated with Masson's trichrome staining (r = -626, P < 0.0014 and r = -0.468, P = 0.01, respectively). CONCLUSION: DKI may be a non-invasive method for monitoring renal interstitial fibrosis induced by hyperuricemia.

The whitening efficacy of a compound formula examined using an ultraviolet-induced skin melanization model.

BACKGROUND: In Eastern culture, a fair complexion is the standard of beauty, leading to appearance-related distress among women with darker skin or facial pigmentation. Women seek whitening cosmetics to enhance their skin tone or correct their pigmentation, but their safety and effectiveness are paramount factors to consider. In this study, we evaluated the safety and whitening effects of a compound formula denoted as TEST comprising astaxanthin, nicotinamide, arbutin, and tranexamic acid. METHODS: Primary skin irritation and skin-whitening efficacy were examined. Three qualified melanization areas were treated with TEST, 7% ascorbic acid, or a blank. Skin color, the individual type angle (ITA°), and the melanin index (MI) were compared among treatment areas. RESULTS: TEST did not induce a skin response and exhibited a significantly higher ITA° than the blank, while no significant difference was observed with that of 7% ascorbic acid. Furthermore, the MI of TEST was significantly reduced posttreatment. CONCLUSIONS: TEST could be integrated into spot-fading and skin-whitening cosmeceuticals or functional cosmetics.

Application of bedside HINTS, ABCD2 score and truncal ataxia to differentiate cerebellar-brainstem stroke from vestibular neuritis in the emergency room.

BACKGROUND AND PURPOSE: Acute vestibular syndrome (AVS) typically manifests as isolated dizziness or vertigo with no apparent neurological impairments. However, distinguishing life-threatening stroke from innocuous peripheral vestibular lesions in the emergency room (ER) remains challenging. This study aimed to explore the ability of the head impulse-nystagmus-test of skew (HINTS) combined with truncal ataxia or ABCD2 score to differentiate stroke from peripheral vestibular disease in patients with AVS in the ER. METHODS: We prospectively recruited 121 patients with AVS from December 2022 to June 2023, 69 of whom presented with vestibular neuritis (VN) and the remaining with posterior circulation stroke (PCS). We analysed the HINTS results, truncal ataxia and ABCD2 score and compared the sensitivity and specificity among HINTS, truncal ataxia, ABCD2 score and their combinations using the McNemar test for paired samples. RESULTS: HINTS combined with grade 2-3 truncal ataxia achieved significantly higher sensitivity than that of isolated HINTS in differentiating PCS from VN (100% vs 88.5%, p=0.031). The specificity of HINTS plus grade 2-3 truncal ataxia did not significantly differ from that of isolated HINTS (p=0.125); however, the combination of ABCD2 score and HINTS did not improve the diagnostic accuracy. The sensitivity of ABCD2 score ≥4 plus grade 2-3 truncal ataxia was significantly higher than those of isolated ABCD2 score ≥4 or isolated grade 2-3 truncal ataxia (p=0.016 and p<0.001, respectively) and not significantly lower than that of isolated HINTS (p=0.508). CONCLUSION: Compared with the ABCD2 score, the truncal ataxia is of more valuable assistance to HINTS in differentiating PCS. Although the combination of ABCD2 score and truncal ataxia has a significant implication, it is not a replacement for HINTS.

Unveiling the biointerfaces characteristics and removal pathways of Cr(â ¥) in Bacillus cereus FNXJ1-2-3 for the Cr(â ¥)-to-Cr(0) conversion.

Although less toxic than hexavalent chromium, Cr (Ⅲ) species still pose a threat to human health. The Cr (Ⅵ) should be converted to Cr (0) instead of Cr (Ⅲ), which is still involved in biological detoxification filed. Herein, for the first time, it was found that Cr(Ⅵ) can be reduced into Cr(0) by Bacillus cereus FNXJ1-2-3, a way to completely harmless treatment of Cr(Ⅵ). The bacterial strain exhibited excellent performance in the reduction, sorption, and accumulation of Cr(Ⅵ) and Cr (Ⅲ). XPS etching characterization inferred that the transformation of Cr(Ⅵ) into Cr(0) followed a reduction pathway of Cr(Ⅵ)→Cr (Ⅲ)→metallic Cr(0), in which at least two secretory chromium reductases (ECrⅥ→Ⅲ and ECrⅢ→0) worked. Under the optimum condition, the yield ratio of Cr(0)/Cr (Ⅲ) reached 33.90%. In addition, the interfacial interactions, ion channels, chromium reductases, and external electron donors also contributed to the Cr(Ⅵ)/Cr(0) transformation. Findings of this study indicate that Bacillus cereus FNXJ1-2-3 is a promising bioremediation agent for Cr(Ⅵ) pollution control.

Estimation of spatial distribution of soil moisture on steep hillslopes by state-space approach (SSA).

Soil moisture is a critical variable that quantifies precipitation, floods, droughts, irrigation, and other factors with regard to decision-making and risk evaluation. An accurate prediction of soil moisture dynamics is important for soil and environmental management. However, the complex topographic condition and land use in hilly and mountainous areas make it a challenge to monitor and predict soil moisture dynamics in these areas. In this study, the determinants of soil moisture variability were determined by structural equation modeling, and then an attempt was made to estimate the spatial distribution of soil moisture content on steep hillslope using the state-space method. Herein, soil moisture at different depths (0-10, 10-20, and 20-30 cm) was monitored by portable time-domain reflectometer (TDR) along this hillslope (100 m × 180 m). It showed that the spatial variability of soil moisture decreased with increasing soil wetness, primarily in the topsoil (0-10 cm). Soil moisture was correlated with elevation (r = 0.28, 0.50, and 0.28), capillary porosity (r = 0.06, 0.37, and 0.28), soil texture (r for Clay: 0.20, 0.24, and 0.16; r for Sand: -0.25, -0.18, and -0.28), organic carbon (r = -0.31, -0.08, and 0.10) and land use (r = -0.01, 0.28, and 0.24) under different conditions (dry, moderate, and wet). Among these determinants, elevation made direct contributions to soil moisture variation, especially under moderate conditions, while land use made its impacts by altering soil texture. It is encouraging that the state-space approach yielded precise and cost-effective predictions of soil moisture dynamics along this steep hillslope since it gives the minimum root-mean-square error (RMSE) and Akaike information criterion (AIC). Moreover, soil organic carbon (AIC = -4.497, RMSE = 0.104, R2 = 0.899), rock fragment contents (AIC = -4.366, RMSE = 0.111, R2 = 0.878), and elevation (AIC = -3.693, RMSE = 0.156, R2 = 0.629) effectively anticipated the spatial distribution of soil moisture under dry, moderate, and wet conditions, respectively. This study confirms the efficacy of the state-space approach as a valuable tool for soil moisture prediction in areas characterized by complex and spatially heterogeneous conditions.

[Prenatal diagnosis and outcome of pregnancy for women with high risks by screening of fetal free DNA from peripheral blood samples].

OBJECTIVE: To analyze the results of prenatal diagnosis and outcome of pregnancy for women with a high risk for fetal aneuploidies. METHODS: A total of 747 cases of prenatal diagnosis by amniocentesis due to high risks by non-invasive prenatal testing (NIPT) were selected from January 2015 to March 2022 in the Drum Tower Hospital Affiliated to Nanjing University Medical School. The amniotic fluid samples were subjected to chromosomal karyotyping and/or chromosomal microarray analysis. All cases were followed up by searching the birth information or telephone calls, and the results were recorded. 2 test or F test were used for comparing the difference between the groups. RESULTS: Among the 747 pregnant women with a high risk by NIPT, 387 were true positives, and the overall positive predictive value (PPV) was 51.81%. The PPVs for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13) and sex chromosome aneuploidies (SCA) were 80.24% (199/248), 60% (48/80), 14% (7/50) and 38.97% (106/272), respectively. The PPV for T21 was significantly higher than T18 and T13 (χ2 = 85.216, P < 0.0001). The PPV for other chromosomal aneuploidies and copy number variations (CNVs) were 11.11% (5/45) and 40.74% (22/52), respectively. The PPV for increased X chromosomes was significantly higher than X chromosome decreases (64.29% vs. 22.22%, χ2 = 5.530, P < 0.05). The overall PPV for elder women (≥ 35 years old) was significantly higher than younger women (69.35% vs. 42.39%, χ2 = 49.440, P < 0.0001). For T21 and T18, the PPV of Z ≥ 10 group was significantly higher than that for 3 ≤ Z < 5 group or 5 ≤ Z < 10 group (P < 0.05). Among 52 cases with a high risk for CNVs, the PPV for the ≤ 5 Mb group was significantly higher than the 5 Mb < CNVs < 10 Mb or > 10 Mb groups (60% vs. 30%60% vs. 23.53%, P < 0.05). Among the 387 true positive cases, 322 had opted for induced labor, 53 had delivered with no abnormal growth and development, and 12 were lost during the follow-up. CONCLUSION: The PPVs for common chromosomal aneuploidies are related to the age and Z value of the pregnant women, which were higher in the elder group and higher Z value group. In addition, the PPV is associated with high risk types. The PPV for T21 was higher than T18 and T13, and that for 45,X was lower than 47,XXX, 47,XYY or 47,XXY syndrome. NIPT therefore has relatively high PPVs for the identification of chromosomal CNVs.

Energy preservation for skeletal muscles: Shenqi Fuzheng injection prevents tissue wasting and restores bioenergetic profiles in a mouse model of chemotherapy-induced cachexia.

BACKGROUND: Energy deficiency is the characteristic of chemotherapy-induced cachexia (CIC) which is manifested by muscle wasting. glycolysis, tricarboxylic acid (TCA) cycle, and lipid metabolism are central to muscle bioenergy production, which is vulnerable to chemotherapy during cancer treatment. Recent investigations have spotlighted the potential of Shenqi Fuzheng injection (SQ), a Chinese proprietary medicine comprising Radix Codonopsis and Radix Astragali, in alleviating CIC. However, the specific effects of SQ on muscle energy metabolism remains less explored. PURPOSE AND METHODS: Here, we integrated transcriptomics, spatial metabolomics, gas chromatography-mass spectrometry targeted quantitative analysis, and transmission electron microscopy techniques, combined with Seahorse live-cell metabolic analysis to reveal the changes in genes and pathways related to energy metabolism in the CIC model and SQ's protective effects at molecular and functional levels. RESULTS: Our data showed that chemotherapeutic agents caused glycolysis imbalance, which further leads to metabolic derangements of TCA cycle intermediates. SQ maintained glycolysis balance by facilitating pyruvate fluxing to mitochondria for more efficient bioenergy production, which involved a dual effect on promoting functions of mitochondrial pyruvate dehydrogenase complexes and inhibiting lactate dehydrogenase for lactate production. As a result of the sustained pyruvate level achieved by SQ administration, glycolysis balance was maintained, which further led to the preservation of mitochondrial integrity and function of electron transport chain, thereby, ensuring the normal operation of the TCA cycle and the proper synthesis of adenosine triphosphate (ATP). The above results were further validated using the Seahorse live-cell assay. CONCLUSION: In conclusion, our study highlights SQ as a promising strategy for CIC management, emphasizing its ability to harmonize the homeostasis of the muscle bioenergetic profile. Beyond its therapeutic implications, this study also offers a novel perspective for the development of innovative treatments in the realm of herbal medicine.

Oriented polyaniline/poly-l-lactic acid/gelatin nanofiber scaffolds promote outgrowth of spiral ganglion neurons.

Sensorineural hearing loss (SNHL) is caused by the loss of sensory hair cells (HCs) and/or connected spiral ganglion neurons (SGNs). The current clinical conventional treatment for SNHL is cochlear implantation (CI). The principle of CI is to bypass degenerated auditory HCs and directly electrically stimulate SGNs to restore hearing. However, the effectiveness of CI is limited when SGNs are severely damaged. In the present study, oriented nanofiber scaffolds were fabricated using electrospinning technology to mimic the SGN spatial microenvironment in the inner ear. Meanwhile, different proportions of polyaniline (PANI), poly-l-lactide (PLLA), gelatin (Gel) were composited to mimic the composition and mechanical properties of auditory basement membrane. The effects of oriented PANI/PLLA/Gel biomimetic nanofiber scaffolds for neurite outgrowth were analyzed. The results showed the SGNs grew in an orientation along the fiber direction, and the length of the protrusions increased significantly on PANI/PLLA/Gel scaffold groups. The 2% PANI/PLLA/Gel group showed best effects for promoting SGN adhesion and nerve fiber extension. In conclusion, the biomimetic oriented nanofiber scaffolds can simulate the microenvironment of SGNs as well as promote neurite outgrowth in vitro, which may provide a feasible research idea for SGN regeneration and even therapeutic treatments of SNHL in future.

Established sensitization of ethanol-induced locomotor activity is not reversed by psilocybin or the 5-HT2A receptor agonist TCB-2 in male DBA/2J mice.

RATIONALE: Psychedelic drugs, which share in common 5-HT2A receptor agonist activity, have shown promise in treating alcohol-use disorders (AUDs). Repeated exposure to ethanol (EtOH) induces molecular and behavioural changes reflective of neuroadaptations that may contribute to addiction. Psychedelic drugs can induce neuroplasticity also, raising the possibility that their potential clinical effects in AUD may involve an action to reverse or offset effects of long-term changes induced by EtOH. This possibility was examined by investigating whether psilocybin, or the 5-HT2A receptor agonist TCB-2, counteracted established sensitization of EtOH-induced locomotor activity. METHODS: Male DBA/2J mice received repeated injections of 2.2 g/kg EtOH to induce a sensitized locomotor activity response. In two experiments separate groups of mice were then injected with psilocybin (0, 0.3 and 1 kg/kg) or TCB-2 (0, 1 and 3 mg/kg) on 5 consecutive days. Next, mice were challenged with 1.8 g/kg EtOH and locomotor activity measured for 15 min. RESULTS: Relative to naïve controls, previously sensitized mice showed enhanced locomotor activity to the challenge dose. Despite reducing locomotor activity in their own right psilocybin and TCB-2 did not alter the strength of this sensitized response. CONCLUSION: Psilocybin and TCB-2 at behaviourally effective doses did not reverse sensitization of EtOH-induced activity. This suggests that mechanisms involved in mediating short-term reductions in EtOH intake by psilocybin or TCB-2 may not involve a capacity of these drugs to offset enduring changes in behaviour and any underlying neural adaptations induced by repeated intermittent exposure to EtOH.

Identification of odor-causing compounds in six species of odor-producing microalgae separated from drinking water source with distinct fishy odor: Insight into microalgae growth and odor characteristics.

Fishy odor, as an offensive and unpleasant odor, could occur in drinking water source with poor nutrition, it is usually considered to be associated with odor-producing microalgae. However, the specific relations among fishy odor, fishy odorants and responsible microalgae were not elucidated comprehensively. In this paper, the odor-causing compounds generated from six microalgae with fishy odor characteristic, isolated in drinking water source Tongyu River, were identified simultaneously. The sensory evaluation result indicated that Tongyu River was principally related to fishy odor (odor intensity 6.5-7.6). Correspondingly, seven, nine, seven, six, seven and seven olfactory detection peaks (ODP) were screened by combining data of GC/O/MS and GC/GC/TOFMS in Cyclotella, Cryptomonas ovate, Melosira, Dinobryon sp., Synedra and Ochromonas sp., which were isolated in Tongyu River and cultured in laboratory. Totally twenty odor-causing compounds, including hexanal, 2-hexenal, 3-hexen-1-ol, heptanal, 1-octen-3-one, 2,4-heptadienal, 2-tetradecanone, 3,5-octadien-2-one, octanal, 1-octen-3-ol, 2-octenal, nonanal, 2,4-octadienal, 2-nonenal, decanal, 2,6-nonadienal, 2-decenal, undecanal, 2,4-decadienal and dodecanal, were screened and identified in all isolated microalgae. Additionally, fishy odor intensity for all identified microalgae increased obviously as microalgae cell number increased and microalgae cell ruptured in cultivation cycles through pearson and spearman correlation analysis. For the first time, twenty odor-causing compounds associating with fishy odor were recognized from six isolated microalgae, which would provide more scientific basis and theoretical support for preventing and treating fishy odor episode of drinking water source.

Effects of psilocybin, the 5-HT2A receptor agonist TCB-2, and the 5-HT2A receptor antagonist M100907 on visual attention in male mice in the continuous performance test.

RATIONALE: Neuropsychiatric disorders such as depression are characterized in part by attention deficits. Attention is modulated by the serotonin (5-HT) neurotransmitter system. The 5-HT2A agonist and hallucinogen psilocybin (PSI) is a promising treatment for disorders characterized by attention changes. However, few studies have investigated PSI's direct effect on attention. OBJECTIVE: Using the rodent continuous performance task (CPT), we assessed PSI's effect on attention. We also evaluated the impact of 5-HT2A receptor agonist TCB-2 and antagonist M100907 for comparative purposes. METHODS: In the CPT, mice learned to distinguish visual targets from non-targets for milkshake reward. Performance was then tested following injections of PSI (0.3, 1, and 3 mg/kg), TCB-2 (0.3, 1, and 3 mg/kg), or M100907 (0.1, 0.3, and 1 mg/kg). Subsequently, drug effects were then evaluated using a more difficult CPT with variable stimulus durations. Mice were then tested on the CPT following repeated PSI injections. Drug effects on locomotor activity were also measured. RESULTS: In the CPT, all three drugs reduced hit and false alarm rate and induced conservative responding. PSI also reduced target discrimination. These effects were seen primarily at doses that also significantly reduced locomotor activity. No drug effects were seen on the more difficult CPT or following repeated PSI injections. CONCLUSIONS: Psilocybin, TCB-2, and M100907 impaired performance of the CPT. However, this may be in part due to drug-induced locomotor changes. The results provide little support for the idea that psilocybin alters visual attention, or that 5-HT2A receptors modulate this process.

Berberine protects against neomycin-induced ototoxicity by reducing ROS generation and activating the PI3K/AKT pathway.

In mammals, aminoglycoside antibiotic-induced injury to hair cells (HCs) and associated spiral ganglion neurons (SGNs) is irreversible and eventually leads to permanent hearing loss. Efforts have been directed towards the advancement of efficacious therapeutic treatments to protect hearing loss, but the ideal substance for treating the damaged cochlear sensory epithelium has yet to be identified. Berberine (BBR), a quaternary ammonium hydroxide extracted from Coptis chinensis, has been found to display potential anti-oxidant and neuroprotective properties. However, its involvement in aminoglycoside antibiotic-induced ototoxicity has yet to be explored or assessed. In the present study, we explored the possible anti-oxidative properties of BBR in mitigating neomycin-triggered ototoxicity. An improved survival of HCs and SGN nerve fibers (NFs) in organ of Corti (OC) explants after neomycin with BBR co-treatment was observed, and BBR treatment attenuated reactive oxygen species (ROS) generation and reduced cleaved caspase-3 signaling by activating six phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling relative subtypes, and the addition of PI3K/AKT suppressor LY294002 resulted in a decrease in the protective effect. The protective effect of BBR against ototoxicity was also evident in a neomycin-injured animal model, as evidenced by the preservation of HC and SGN in mice administered subcutaneous BBR for 7 days. In summary, all results suggest that BBR has potential as a new and effective otoprotective agent, operating via the PI3K/AKT signaling pathway.

2-Year survival benefit from immunotherapy for squamous cell cancer with cancer of unknown primary in mediastinum: a case report.

Cancers of unknown primary (CUP) account for 2%-5% of all diagnosed cancers and are always characterized with fast-paced aggression, early metastasis, and unpredictable spread patterns Mediastinum metastasis with unknown primary origin is extremely rare and with a poor prognosis and short survival. There is no literature to refer to for its treatment. Here, we reported a case of squamous cell CUP in the mediastinum. A 50-year-old male patient was admitted after multi-line treatment of low differentiated squamous cell carcinoma in the mediastinum diagnosed 8 months before. In August 2019, the patient went to a local hospital for cough and dyspnea for 2 weeks. Then, he was diagnosed with squamous cell carcinoma of unknown primary origin with multiple lymph nodes metastasis. The patient was featured with programmed cell death-ligand 1 (PD-L1) expression strongly positive in 90% of tumor cells and the combined positive score of 90 and a tumor mutation burden of 1.79 MUts/Mb and microsatellite stable phenotype. The patient was treated with anti-programmed cell death-1 (PD-1) antibodies in combination with chemotherapy and responded to the treatment. The patient showed stable disease to multi-line immunotherapy for more than 7 months and finally got a clinical benefit of 2-year survival benefit. In conclusion, immunotherapy targeting PD-1/PD-L1 in combination with chemotherapy may play a crucial role in the later-line treatment and palliative care of CUP.

Design, Synthesis, and Biological Evaluation of N'-Phenylhydrazides as Potential Antifungal Agents.

Fifty-two kinds of N'-phenylhydrazides were successfully designed and synthesized. Their antifungal activity in vitro against five strains of C. albicans (Candida albicans) was evaluated. All prepared compounds showed varying degrees of antifungal activity against C. albicans and their MIC80 (the concentration of tested compounds when their inhibition rate was at 80%), TAI (total activity index), and TSI (total susceptibility index) were calculated. The inhibitory activities of 27/52 compounds against fluconazole-resistant fungi C. albicans 4395 and 5272 were much better than those of fluconazole. The MIC80 values of 14/52 compounds against fluconazole-resistant fungus C. albicans 5122 were less than 4 µg/mL, so it was the most sensitive fungus (TSIB = 12.0). A11 showed the best inhibitory activity against C. albicans SC5314, 4395, and 5272 (MIC80 = 1.9, 4.0, and 3.7 µg/mL). The antifungal activities of B14 and D5 against four strains of fluconazole-resistant fungi were better than those of fluconazole. The TAI values of A11 (2.71), B14 (2.13), and D5 (2.25) are the highest. Further exploration of antifungal mechanisms revealed that the fungus treated with compound A11 produced free radicals and reactive oxygen species, and their mycelium morphology was damaged. In conclusion, the N'-phenylhydrazide scaffold showed potential in the development of antifungal lead compounds. Among them, A11, B14, and D5 demonstrated particularly promising antifungal activity and held potential as novel antifungal agents.

Influence of genetically predicted autoimmune diseases on NAFLD.

Introduction: Non-alcoholic fatty liver disease (NAFLD), the emerging cause of end-stage liver disease, is the most common liver disease. Determining the independent risk factors of NAFLD and patients who need more monitoring is important. Methods: Two-Sample Mendelian randomization (MR) was performed in the analysis to investigate the causal association of different autoimmune diseases with NAFLD using summary level data. Genome-wide association study (GWAS) of 5 autoimmune diseases including celiac disease (CeD), Crohn's disease (CD), multiple sclerosis (MS), rheumatoid arthritis (RA), and type 1 diabetes (T1D) were selected for Instrument variables (IVs). NAFLD was included as outcome. Result: After adjusting for confounding factors, genetic predisposition of CeD (OR= 0.973, [0.949,0.997], IVW p-value=0.026), MS (OR= 1.048, [1.012,1.085], IVW p-value= 0.008), RA (OR= 1.036, [1.006,1.066], IVW p-value=0.019), T1D (OR= 1.039, [1.002,1.079], IVW p-value= 0.041) is causally associated with NAFLD. No causal effect was found between CD and NAFLD. Conclusion: CeD itself may be a protective factor for NAFLD, the results of previous observational studies have been influenced by confounding factors, and the morbidity of NAFLD may be higher in patients with MS, RA, and T1D than in common populations, and monitoring the prevalence of NAFLD in these populations is considerable.

Characteristics and potential human health risks of microplastics identified in typical clams from South Yellow Sea Mudflat.

The ingestion of clams (Meretrix) with microplastics (MP) contamination could pose potential risk to human health. The characteristics and potential risks of MP identified in wild-clam and farm-clam from South Yellow Sea Mudflat were studied comprehensively in this paper. The results indicated that MP were identified in both wild-clam (3.4-21.3 items/individual, 2.11-10.65 items/g) and farm-clam (1.3-20.8 items/individual, 0.62-8.67 items/g) among 21 sampling sites along South Yellow Sea Mudflat. The MP abundance of clams from marine estuarine or coast ports were significantly higher than those from purely marine coast mudflat, implying that environmental habitats played an important role on MP characteristics. MP abundance were significantly and positively related to shell length, shell height, shell width and soft tissue wet weight by Pearson test, suggesting the bigger the shell, there existed more MP abundance. Among MP in wild-clams and farm-clams, fragment, fiber were most abundant MP shapes, most MP's sizes were lower than 0.25 mm, the predominant colors were black, red, blue and transparent, chlorinated polyethylene (CPE) was the major polymer. Additionally, estimated dietary intake (EDI) of MP for adults via consumption of wild-clam and farm-clam were 1123.33 ± 399.97 and 795.07 ± 326.72 items/kg/year, respectively, suggesting EDI values of wild-clams were higher than those of farm-clams, and MP intake via wild-clam consumption were more than that via farm-clam consumption. The polymer risk indexes (PRI) of MP in total tissue and digestive system for wild-clam were 1297.8 ± 92.15 (hazard level: IV ~ V), 1038 ± 69.55 (IV ~ V), respectively, while PRI of MP in total tissue and digestive system for farm-clam were 979.92 ± 75.45 (III ~ IV), 735 ± 47.78 (III ~ IV), respectively, implying that PRI and hazard level of MP from wild-clam were higher than those from farm-clam, and the potential risks would decrease greatly when digestive systems of clams are removed during ingestion.

Production, structural and functional characteristics of soluble dietary fiber from fermented okara by Penicillium expansum.

Soluble dietary fiber (SDF), an important prebiotic, has attracted growing attention, due to its great health effects and wide application. This study focused on the preparation of SDF from fermented okara. The yield of SDF obtained through Penicillium expansum fermentation (FSDF) reached 45.63 % (w/w) under the optimal conditions (pH 6.7, inoculum size 9.5 %, and time 29 h) by response surface methodology, which were 1.92 and 4.43 times higher than those of phosphate-citric acid treatment and untreated okara. Infrared spectra and X-ray diffraction indicated that three SDFs had similar spectral distribution and crystalline region. Moreover, FSDF displayed looser and more porous microstructures. Meanwhile, the composition ratio of monosaccharides has changed. FSDF exhibited higher water solubility (97.46 %), glucose adsorption capacity (203.73 mg/g), sodium cholate adsorption capacity (13.07 mg/g), cholesterol adsorption capacity (6.69- 7.62 mg/g) and radical (ABTS+, hydroxyl and DPPH) scavenging capacity. Additionally, three SDFs didn't degrade by upper gastrointestinal tract and could improve the proportion of beneficial intestinal flora in vitro, such as Lactobacillus and Bifidobacterium. Overall, the FSDF prepared in this study was a functional ingredient with great potential in foods.