Neoadjuvant relatlimab and nivolumab in resectable melanoma.

Relatlimab and nivolumab combination immunotherapy improves progression-free survival over nivolumab monotherapy in patients with unresectable advanced melanoma1. We investigated this regimen in patients with resectable clinical stage III or oligometastatic stage IV melanoma (NCT02519322). Patients received two neoadjuvant doses (nivolumab 480 mg and relatlimab 160 mg intravenously every 4 weeks) followed by surgery, and then ten doses of adjuvant combination therapy. The primary end point was pathologic complete response (pCR) rate2. The combination resulted in 57% pCR rate and 70% overall pathologic response rate among 30 patients treated. The radiographic response rate using Response Evaluation Criteria in Solid Tumors 1.1 was 57%. No grade 3-4 immune-related adverse events were observed in the neoadjuvant setting. The 1- and 2-year recurrence-free survival rate was 100% and 92% for patients with any pathologic response, compared to 88% and 55% for patients who did not have a pathologic response (P = 0.005). Increased immune cell infiltration at baseline, and decrease in M2 macrophages during treatment, were associated with pathologic response. Our results indicate that neoadjuvant relatlimab and nivolumab induces a high pCR rate. Safety during neoadjuvant therapy is favourable compared to other combination immunotherapy regimens. These data, in combination with the results of the RELATIVITY-047 trial1, provide further confirmation of the efficacy and safety of this new immunotherapy regimen.

Clinical and MRI risk factors predicting post-irradiation carotid blowout syndrome in patients with nasopharyngeal cancer.

OBJECTIVE: To explore the clinical and imaging features of nasopharyngeal cancer (NPC) complicated by acute carotid blowout syndrome (CBS), analyze the risk factors for CBS, and improve diagnostic vigilance for early intervention. METHODS: This retrospective review was conducted between January 2003 and May 2023. Altogether, 49 patients with post-irradiation NPC with CBS and 49 patients without CBS as control group were enrolled. The condition of the patients when CBS occurred was reviewed. Patient characteristics of the CBS and control groups were compared, and binary logistic regression analysis was performed to identify risk factors for CBS. RESULTS: All patients in the CBS group were conscious, and 41 patients had a Karnofsky performance assessment scale score of ≥ 70. After interventional therapy, 43 patients survived (the mean survival time of patients after CBS was 3.2 ± 2.1 years). Compared with the control group, the CBS group had a higher incidence of sphenoid sinusitis (81% vs. 52.4%), osteonecrosis (82.9% vs. 51.2%), artery exposure (29.3% vs. 4.9%), and internal carotid artery injury (61% vs. 29.3%). Osteonecrosis and artery exposure were selected as important risk factor for CBS, with p-values of 0.016 and 0.031, respectively. CONCLUSION: CBS is an important factor that affects the survival of patients with NPC. If internal carotid artery injury, artery exposure, sphenoid sinusitis, and osteonecrosis are present, especially the latter two signs, the possibility of CBS should be considered.

Assessing Visual Pathway White Matter Degeneration in Primary Open-Angle Glaucoma Using Multiple MRI Morphology and Diffusion Metrics.

BACKGROUND: Primary open-angle glaucoma (POAG), a leading cause of irreversible blindness, is associated with neurodegeneration in the visual pathway, but the underlying pathophysiology remains incompletely resolved. PURPOSE: To characterize macro- and microstructural white matter abnormalities in optic tract (OT) and optic radiation (OR) of POAG. STUDY TYPE: Prospective. POPULATIONS: A total of 34 POAG patients (21 males, 13 females) and 25 healthy controls (HCs) (16 males, nine females). FIELD STRENGTH/SEQUENCE: 3 T; multiband spin-echo echo planar diffusion spectrum imaging (DSI). ASSESSMENT: We compared multiple morphology metrics, including volume, area, length, and shape metrics, as well as diffusion metrics such as diffusion tensor imaging (fractional anisotropy [FA], mean diffusivity, radial diffusivity, and axial diffusivity), mean apparent propagator (mean squared displacement, q-space inverse variance, return-to-origin probability, return-to-axis probabilities [RTAP] and return-to-plane probabilities, non-Gaussianity, perpendicular non-Gaussianity, parallel non-Gaussianity), and neurite orientation dispersion and density imaging (intracellular volume fraction, orientation dispersion index [ODI], and isotropic volume fraction of the OT and OR). STATISTICAL TESTS: Statistical comparisons and classifications employed linear mixed model and logistic regression. Diagnostic performance was assessed using area under the receiver operating characteristic curve (AUC). P-value <0.05 was statistically significant. RESULTS: Morphology analysis in POAG revealed a lower span in the OR (29.43 ± 2.30 vs. 30.59 ± 2.01, 3.8%) and OT (19.73 ± 2.21 vs. 20.68 ± 1.37, 4.6%), and a higher curl (3.03 ± 0.22 vs. 2.90 ± 0.16, 4.5%) in OT. Diffusion metrics revealed lower mean FA (OR: 0.328 ± 0.03 vs. 0.340 ± 0.018, 3.5%; OT: 0.255 ± 0.022 vs. 0.268 ± 0.018, 4.9%) and lower mean RTAP (OR: 5.919 ± 0.529 vs. 6.216 ± 0.489, 4.8%; OT: 4.089 ± 0.402 vs. 4.280 ± 0.353, 4.5%), with higher mean ODI in the OT (0.448 ± 0.029 vs. 0.433 ± 0.025, 3.5%). Combined models, incorporating these MRI metrics, effectively discriminated POAG from HCs, achieving AUCs of 0.84 for OR and 0.83 for OT. DATA CONCLUSIONS: DSI-derived morphology and diffusion metrics demonstrated macro- and micro abnormalities in the visual pathway, providing insights into POAG-related neurodegeneration. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Effects of Inorganic Salts on the Phase Separation of Partially Miscible Solutes.

Partially miscible solutions with a lower critical solution temperature have promising applications in the field of physical chemistry. To better guide the utilization of these solutions in practice, we conduct an in-depth study about the phase separation behavior of the solution added with inorganic salts. The addition of the inorganic salts into the solution is found to consequently reduce the phase separation temperature. The variation of concentrations of inorganic salts does not notably affect the mass fraction of the separation. Moreover, the addition of inorganic salts in the solutions at lower mass fractions improves the separation mass fraction, while the addition of inorganic salts decreases the separation mass fraction at the mass fractions above 30%. It sheds light on selecting the proper mass fractions and inorganic salt concentrations. Furthermore, we explore the phase separation behavior of mixed solutions under different inorganic salt additions by means of a high-speed camera. The phase separation behavior under different inorganic salt systems shows a similar trend. However, calcium ions and Fe3+ ions in the solutions can greatly decrease the rate of droplet coalescence and result in an increase in phase separation. For better regulating the solutions with a lower critical solution temperature through inorganic salts, sodium chloride or potassium chloride is recommended with an appropriate concentration.

Administration of silymarin in NAFLD/NASH: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a high prevalence worldwide and poses serious harm to human health. There is growing evidence suggesting that the administration of specific supplements or nutrients may slow NAFLD progression. Silymarin is a hepatoprotective extract of milk thistle, but its efficacy in NAFLD remains unclear. MATERIALS AND METHODS: Relevant studies were searched in PubMed, Embase, the Cochrane Library, Web of Science, clinicaltrails.gov, and China National Knowledge Infrastructure and were screened according to the eligibility criteria. Data were analyzed using Revman 5.3. Continuous values and dichotomous values were pooled using the standard mean difference (SMD) and odds ratio (OR). Heterogeneity was evaluated using the Cochran's Q test (I2 statistic). A P<0.05 was considered statistically significant. RESULTS: A total of 26 randomized controlled trials involving 2,375 patients were included in this study. Administration of silymarin significantly reduced the levels of TC (SMD[95%CI]=-0.85[-1.23, -0.47]), TG (SMD[95%CI]=-0.62[-1.14, -0.10]), LDL-C (SMD[95%CI]=-0.81[-1.31, -0.31]), FI (SMD[95%CI]=-0.59[-0.91, -0.28]) and HOMA-IR (SMD[95%CI]=-0.37[-0.77, 0.04]), and increased the level of HDL-C (SMD[95%CI]=0.46[0.03, 0.89]). In addition, silymarin attenuated liver injury as indicated by the decreased levels of ALT (SMD[95%CI]=-12.39[-19.69, -5.08]) and AST (SMD[95% CI]=-10.97[-15.51, -6.43]). The levels of fatty liver index (SMD[95%CI]=-6.64[-10.59, -2.69]) and fatty liver score (SMD[95%CI]=-0.51[-0.69, -0.33]) were also decreased. Liver histology of the intervention group revealed significantly improved hepatic steatosis (OR[95%CI]=3.25[1.80, 5.87]). CONCLUSIONS: Silymarin can regulate energy metabolism, attenuate liver damage, and improve liver histology in NAFLD patients. However, the effects of silymarin will need to be confirmed by further research.

First Report of Neoscytalidium dimidiatum causing leaf zonate spot disease of Aloe vera L. in China.

In February 2022, leaf zonate spot disease afflicted Aloe vera L. in Yunnan, China, endangering the $39 billion industry with 0.33ha under cultivation (Wan 2015). The disease manifested with watery spots progressing into oval or circular necrosis lesions, characterized by a dark center surrounded by a gray-brown zone. In the late stage of the disease, lesions regress in size and several small dark picnidia dots appeared on the gray-brown zone. The disease incidence ranged from 10% to 15% in three commercial plantations. If left uncontrolled, the disease could diminish the commercial value of Aloe vera plants. Eighteen symptomatic leaf samples underwent morphological and genetic identification. The samples were carefully washed with distilled water and 1×1 cm2 sections of tissue were excised using a sterile scalpel. The sections underwent surface-disinfection with 3% NaOCl for 3 min and 75% ethanol for 30 s. After three sterile water rinses the sections were air-dried. Subsequently, they were transferred to potato dextrose agar (PDA) before being incubated at 25 ℃ in the dark. Of the 18 samples, eight produced the colonies with similar morphological characteristics, named LH7. Isolate LH7 had downy to woolly aerial mycelia, initially pinkish white on the surface, and gradually turned greenish-olivaceous from the middle, and eventually turned dark brown to black after seven days. The fungus formed arthric chains in the aerial mycelium on PDA but did not produce conidiomata. The conidia, which occurred in arthric chains were 5.50-9.9 × 4.08-7.51 µm (mean 7.09× 5.26 µm, n=50) in size, cylindrical, brown, and 0-1 septate. To ascertain LH7's pathogenicity, three healthy one-year old aloe plants were surface-sanitized with a 1% aqueous chlorine solution, rinsed with sterile water, and dried. Three leaves from each plant were punctuated and inoculated using conidial suspension (100 µl of 1x 106 conidial mL-1), while three control plants were inoculated with sterile distilled water. The pathogenicity tests were repeated twice. The inoculated plants were kept at 25 ℃ with a 12-hour light/12-hour dark cycle. After seven days, symptoms observed in the field appeared in the plants, while no disease occurred in the control plants. After 21 days, conidiomata formed on the inoculated leaves, averaging 116.92 µm (n=20) in diameter. These conidiomata were globose to subglobose, and brown to sub-brown. The fungus was successfully re-isolated from symptomatic tissue and the resulting colonies were morphologically consistent with isolate LH7. Based on the characteristics, the fungus was identified as Neoscytalidium dimidiatum (Philips et al. 2013). The specimen was deposited in China Center for Type Culture Collection ( CCTCC AF 2024001). This identification was confirmed through sequencing of ITS gene region of rDNA using ITS1/ITS4 (Imran et al. 2022). The sequence was submitted into GenBank database (ON878059). BLAST analysis of the LH7's ITS amplicon showed 100% similarity with that of JN093303.1. A phylogenetic tree constructed using the maximum likelihood method revealed that ON878059 was clustered with JN093303.1. Previous studies have documented that pathogens such as Colletotrichum gloeosporioides (Penz.), Fusarium spp. and Rhizopus oryzae can also cause diseases in A. vera in China (Zhou et al. 2008; Ding et al. 2015). Additinonally, Cladosporium sphaerospermum, Pseudopestalotiopsis theae, and Lasiodiplodia theobromae have been identified as causal agents of aloe leaf spot diseases in India, Bangladesh and Malaysia (Avasthi et al. 2016; Ahmmed et al. 2022; Khoo et al. 2022). To our knowledge, this is the first report of N. dimidiatum causing leaf necrosis of aloe in China. Vigilant surveillance and disease control measures are imperative to mitigate potential losses in this region.

The alterations of brain network degree centrality in patients with neovascular glaucoma: a resting-state fMRI study.

PURPOSE: To explore the alterations of whole brain functional network using the degree centrality (DC) analysis in neovascular glaucoma (NVG) and the correlation between DC values and NVG clinical indices. MATERIALS AND METHODS: Twenty NVG patients and twenty normal controls (NC), closely matched in age, sex, and education, were recruited for this study. All subjects underwent comprehensive ophthalmologic examinations and a resting-state functional magnetic resonance imaging (rs-fMRI) scan. The differences in DC values of brain network between NVG and NC groups were analyzed, and correlation analysis was performed to explore the relationships between DC values and clinical ophthalmological indices in NVG group. RESULTS: Compared with NC group, significantly decreased DC values were found in the left superior occipital gyrus and left postcentral gyrus, while significantly increased DC values in the right anterior cingulate gyrus and left medial frontal gyrus in NVG group. (All P < 0.05, FDR corrected). In the NVG group, the DC value in left superior occipital gyrus showed significantly positive correlations with retinal nerve fiber layer (RNFL) thickness (R = 0.484, P = 0.031) and mean deviation of visual field (MDVF) (R = 0.678, P = 0.001). Meanwhile, the DC value in the left medial frontal gyrus demonstrated significantly negative correlations with RNFL (R = - 0.544, P = 0.013) and MDVF (R = - 0.481, P = 0.032). CONCLUSIONS: NVG exhibited decreased network degree centrality in visual and sensorimotor brain regions and increased degree centrality in cognitive-emotional processing brain region. Additionally, the DC alterations might be complementary imaging biomarkers to assess disease severity.

N-Terminal Lysozyme Conjugation to a Cationic Polymer Enhances Antimicrobial Activity and Overcomes Antimicrobial Resistance.

Microbial resistance to antibiotics is one of the greatest global healthcare challenges. There is an urgent need to develop effective strategies to overcome antimicrobial resistance. We, herein, report photoinduced in situ growth of a cationic polymer from the N-terminus of lysozyme. The attachment of the cationic polymer improves the proteolytic and thermal stability of lysozyme. Notably, the conjugate can efficiently overcome lysozyme resistance in Gram-positive bacteria and antibiotics-resistance in Gram-negative bacteria, which may be ascribed to the synergistic interactions of lysozyme and the cationic polymer with the bacteria to disrupt their cell membranes. In a rat periodontitis model, the lysozyme-polymer conjugate not only greatly outperforms lysozyme in therapeutic efficacy but also is superior to minocycline hydrochloride, which is the gold standard for periodontitis therapy. These findings may provide an efficient strategy to dramatically enhance the antimicrobial activities of lysozyme and pave a way to overcome antimicrobial resistance.

Ligustrazine Attenuates Liver Fibrosis by Targeting miR-145 Mediated Transforming Growth Factor-ß/Smad Signaling in an Animal Model of Biliary Atresia.

To investigate therapeutic target for ligustrazine during liver fibrosis in an ethanol-induced biliary atresia rat model and transforming growth factor-ß (TGF-ß) induced hepatic stellate cell activation cell model, and the underlying mechanism, a total of 30 rats were randomly assigned into five groups (n = 6 per group): control, sham, ethanol-induced biliary atresia model, model plus pirfenidone, and model plus ligustrazine groups. The liver changes were assessed using H&E and Masson staining and transmission electron microscopy. Expression of miR-145 and mRNA and protein levels of TGF-ß/smads pathway-related proteins were detected. HSC-T6 cells were infected with LV-miR or rLV-miR-145 in the presence or absence of SMAD3 inhibitor SIS3 and treated with 2.5 ng/ml TGF-ß1 and then with ligustrazine. Collected cells were subjected to detect the expression of miR-145 and mRNA and protein expression levels of TGF-ß/smads pathway-related proteins. Ligustrazine rescued liver fibrogenesis and pathology for ethanol-caused bile duct injury, revealed by decreased α-smooth muscle actin and collagen I expression and liver tissue and cell morphology integrity. Further experiments showed that ligustrazine inhibited intrinsic and phosphorylated Smad2/3 protein expression and modification. Similar results were obtained in cells. In addition, ligustrazine altered miR-145 expression in both animal and cell models. Lentivirus mediated miR-145 overexpression and knockdown recombinant virus showed that miR-145 enhanced the TGF-ß/Smad pathway, which led to hepatic stellate cell activation, and ligustrazine blocked this activation. This work validated that ligustrazine-regulated miR-145 mediated TGF-ß/Smad signaling to inhibit the progression of liver fibrosis in a biliary atresia rat model and provided a new therapeutic strategy for liver fibrosis. SIGNIFICANCE STATEMENT: With an ethanol-induced biliary atresia rat model, ligustrazine was found to rescue liver fibrogenesis and pathology for ethanol caused bile duct injury, revealed by decreased α-smooth muscle actin and collagen I expression and liver tissue and cell morphology integrity. Furthermore, we found ligustrazine upregulated miR-145 expression and inhibited TGF-ß/SMAD signaling pathway both in vivo and in vitro. In addition, overexpression and knockdown of miR-145 confirmed that miR-145 is involved in the ligustrazine inhibition of liver fibrosis through the TGF-ß/SMAD signaling pathway.

Metabolic alterations in the visual pathway of retinitis pigmentosa rats: A longitudinal multimodal magnetic resonance imaging study with histopathological validation.

Because retinitis pigmentosa (RP) has been shown to cause degenerative changes in the entire visual pathway, there is an urgent need to perform longitudinal assessments of RP-induced degeneration and identify imaging protocols to detect this degeneration as early as possible. In this study, we assessed a transgenic rat model of RP by using complementary noninvasive magnetic resonance imaging techniques, namely, proton magnetic resonance spectroscopy (1 H-MRS), to investigate the metabolic changes in RP. Our study demonstrated decreased concentrations and ratios to creatine (Cr) of N-acetylaspartate (NAA), glutamate (Glu), γ-aminobutyric acid (GABA), and taurine (Tau), whereas myo-inositol (Ins) and choline (Cho) were increased in the visual cortex of Royal College of Surgeons (RCS) rats compared with control rats (p < 0.05). Furthermore, with the progression of RP, the concentrations of NAA, Glu, GABA, and Tau, and the ratios of GABA/Cr and Tau/Cr significantly decreased over time, whereas the concentrations of Ins and Cho and the ratio of Ins/Cr significantly increased over time (p < 0.05). In addition, in RCS rats, NAA/Cr decreased significantly from 3 to 4 months postnatal (p < 0.001), and Cho/Cr increased significantly from 4 to 5 months postnatal (p = 0.005). Meanwhile, the 1 H-MRS indicators in 5-month postnatal RCS rats could be confirmed by immunohistochemical staining. In conclusion, with the progression of RP, the metabolic alterations in the visual cortex indicated progressive reprogramming with the decrease of neurons and axons, accompanied by the proliferation of gliocytes.

Thermosensitive Polymer Conjugated Prodrug-Activating Enzyme with Enhanced Tumor Retention and Antitumor Efficacy.

Enzyme-activated prodrug therapy has emerged as an effective strategy for cancer therapy. However, the inefficient delivery of prodrug-activating enzymes into tumor tissues leads to unsatisfactory antitumor efficacy and undesirable toxicity to normal tissues. Herein, we report in situ growth of a thermosensitive polymer of poly(diethylene glycol) methyl ether methacrylate (PDEGMA) from horseradish peroxidase (HRP) to yield a HRP-PDEGMA conjugate with well-retained activity as compared to HRP. The conjugate shows a sharp phase transition behavior with a lower critical solution temperature of 23 °C. The conjugate catalyzes the conversion of non-cytotoxic indole-3-acetic acid (IAA) into cytotoxic species for killing tumor cells. Notably, the PDEGMA conjugation not only increases the stability and cellular uptake of HRP but also prolongs the tumor retention time of HRP upon intratumoral injection. As a result, in mice bearing melanoma, the conjugate inhibits the growth of melanoma much more efficiently than HRP. These results demonstrate that the thermosensitive polymer conjugation of an enzyme is an effective strategy that can enhance the antitumor efficacy of an enzyme-activated prodrug.

Molecular simulation of enhanced separation of humid air components using GO-PVA nanocomposite membranes under differential pressures.

Hydrophilic nanocomposite membranes have significant advantages in the separation of water vapor which is the core process in air dehumidification. This paper focuses on exploring the micro-mechanism of enhanced separation using graphene oxide-polyvinyl alcohol (GO-PVA) nanocomposite membranes. The sorption and diffusion behaviors of water vapor and nitrogen in GO-PVA membranes were investigated using molecular dynamics (MD) and Monte Carlo (MC) methods. The study showed that embedding GO into a PVA matrix results in a higher glass transition temperature and fractional free volume. The latter is believed to enhance the diffusivity of gas molecules in polymeric membranes. The interaction between the polymer chains and GO nanoparticles notably promotes the adsorption capacity of water vapor and inhibits nitrogen adsorption in the membrane. A water vapor permeance of 8844.07 Barrer and a separation factor of 3.53 could be achieved with the GO-PVA-0.5 membrane. The analysis confirmed that GO has the same effect on single gas and binary gas mixtures, i.e., increasing the water vapor permeability and selectivity. The calculated water vapor permeance of binary gas is 83% lower than that of single gas permeation. It is expected that this research could provide fundamentals for the optimization and synthesis of gas separation membranes.

Extramedullary Plasmacytoma of the Sinonasal Cavity: Magnetic Resonance Imaging Characteristics With Readout-Segmented Diffusion-Weighted Imaging and Dual-Energy Computed Tomography Features.

PURPOSE: To determine magnetic resonance imaging (MRI) with readout-segmented diffusion-weighted imaging (RESOLVE-DWI) and dual-energy computed tomography (DECT) features of sinonasal extramedullary plasmacytoma (SN-EMP). METHODS: The MRI and/or DECT of 10 patients with SN-EMP confirmed by pathology were retrospectively reviewed. Apparent diffusion coefficient (ADC) values of RESOLVE-DWI were analyzed in 9 patients. The quantitative parameters derived from DECT, including the iodine concentration (IC), effective atomic number, and the slope (k) of spectral attenuation curve, were measured in 3 patients. RESULTS: On conventional MRI, typical lesions were well defined (7 of 9), and isointense to the brain on both T1WI and T2WI (9 of 9). Most lesions presented with marked enhancement on contrast-enhanced T1WI without significant necrosis (8 of 9). Notably, multiple flow-void signals were observed in all lesions (9 of 9). On RESOLVE-DWI, the average ADC value was 0.55 × 10-3 mm2/s, and the normalized ADC value was 0.66 ± 0.04. On DECT, the average values of IC, effective atomic number, and slope (k) was 2.7 mg/mL, 8.62, and 3.8, respectively. CONCLUSIONS: Some typical MRI features (well-defined mass, isointensity to the brain, marked enhancement without obvious cystic changes, multiple flow voids, and a lower ADC value) strongly suggest the diagnosis of SN-EMP. The quantitative parameters derived from RESOLVE-DWI and DECT may provide more information for the diagnosis of SN-EMP.

[Serum metabolomics of chronic obstructive pulmonary disease with lung-Qi deficiency syndrome].

The present study analyzed the potential biomarkers of chronic obstructive pulmonary disease(COPD) with lung-Qi deficiency syndrome by non-targeted metabolomics and explored the biological basis of this syndrome. Blood samples of 96 COPD patients with lung-Qi deficiency syndrome(COPD with lung-Qi deficiency syndrome group) and 106 healthy people(healthy control group) were collected, and the metabolic profiles of both groups were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Multivariate statistical analysis and differential metabolite screening were carried out by using Progenesis QI and Simca-P. Metabolic pathways were constructed through the MetaboAnalyst. Seven potential biomarkers, such as L-cystathionine, protoporphyrinogen Ⅸ, and citalopram aldehyde, were identified. Compared with the results in the healthy control group, the content of citalopram aldehyde, N1-methyl-2-pyridone-5-carboxamide, and 11ß,17ß-dihydroxy-4-androsten-3-one was significantly up-regulated, while that of the other four compounds such as L-cystathionine, dihydrotestosterone, protoporphyrinogen Ⅸ, and D-urobilinogen was down-regulated. These potential biomarkers involved six metabolic pathways, including cysteine and methionine metabolism, porphyrin and chlorophyll metabolism, drug metabolism of cytochrome P450, steroid hormone biosynthesis, glycine, serine, and threonine metabolism, and nicotinate and nicotinamide meta-bolism. This study is expected to provide a certain scientific basis for the research on traditional Chinese medicine syndrome of COPD with lung-Qi deficiency syndrome from the molecular biology level.

Perineural Invasion as a Prognostic Factor in Laryngeal Squamous Cell Cancer: A Matched-Pair Survival Analysis.

BACKGROUND: The purpose of this study was to compare survival outcomes in patients with perineural invasion (PNI)-positive laryngeal squamous cell carcinoma (LSCC) and patients with PNI-negative LSCC. METHODS: A total of 1,272 patients with LSCC, diagnosed between 2008 and 2017, were included in this study. LSCC Patients with and without PNI were matched based on possible confounding factors. Survival analysis was performed using Kaplan-Meier estimates and the Cox proportional hazards model. RESULTS: Of the 1,272 LSCC patients, 118 (9.28%) were positive for PNI. Compared to PNI-negative patients, PNI-positive LSCC patients had significantly worse overall survival (OS) (p = 0.017), disease-specific survival (DSS) (p = 0.034) and recurrence-free survival (RFS) (p = 0.002). After pair matching, cohorts consisted of 118 patients in the PNI-positive group and 118 in the PNI-negative group. Significantly increased risk of OS (HR, 2.17; 95% confidence interval [CI], 1.29-3.61, p = 0.003), DSS (HR, 2.07; 95% CI, 1.32-3.24, p = 0.004) and RFS (HR, 2.65; 95% CI, 1.59-4.40, p < 0.001) was observed after adjustment for prognostic variables. CONCLUSIONS: Patients with PNI-positive LSCC have significantly worse survival outcomes compared to patients with PNI-negative LSCC.

Low-power and high-speed 2 × 2 thermo-optic MMI-MZI switch with suspended phase arms and heater-on-slab structure.

We propose a ${2} \times {2}$ thermo-optic switch with high switching performance. The switch is based on multimode interferometer (MMI) couplers and a Mach-Zehnder interferometer (MZI) structure, where the phase arms are designed as laterally supported suspended ridge waveguides (LSSRWs) with a metallic heater placed on the slab. It is experimentally demonstrated that this switch has a power consumption of 1.07 mW, a thermal time constant ${\sim}{4.7}\;\unicode{x00B5} {\rm s}$, an extinction ratio ${\sim}{30}\;{\rm dB}$, and an insertion loss ${\sim}{0.5}\;{\rm dB}$. Particularly, the corresponding figure of merit (FOM) has been improved by 1 order magnitude compared with general thermo-optic switches. This ${2} \times {2}$ thermo-optic MMI-MZI switch may find potential application for network reconfiguration and on-chip optical information processing.

Transient Prediction of Nanoparticle-Laden Droplet Drying Patterns through Dynamic Mode Decomposition.

Nanoparticle-laden sessile droplet drying has a wide impact on applications. However, the complexity affected by the droplet evaporation dynamics and particle self-assembly behavior leads to challenges in the accurate prediction of the drying patterns. We initiate a data-driven machine learning algorithm by using a single data collection point via a top-view camera to predict the transient drying patterns of aluminum oxide (Al2O3) nanoparticle-laden sessile droplets with three cases according to particle sizes of 5 and 40 nm and Al2O3 concentrations of 0.1 and 0.2 wt %. Dynamic mode decomposition is used as the data-driven learning model to recognize each nanoparticle-laden droplet as an individual system and then apply the transfer learning procedure. Along 270 s of droplet drying experiments, the training period of the first 100 s is selected, and then the rest of the 170 s is predicted with less than a 10% error between the predicted and the actual droplet images. The developed data-driven approach has also achieved the acceptable prediction for the droplet diameter with less than 0.13% error and a coffee-ring thickness over a range of 2.0 to 6.7 µm. Moreover, the proposed machine learning algorithm can recognize the volume of the droplet liquid and the transition of the drying regime from one to another according to the predicted contact line and the droplet height.

Dendritic nanoparticle self-assembly from drying a sessile nanofluid droplet.

The pattern formation left by a drying nanofluid droplet is related to the evaporation induced particle self-assembly. The experimental results demonstrate the formation of dendritic particle deposition after the liquid phase of unpinned sessile nanofluid droplets is fully evaporated. The dried-in particle assemblies exhibit the dendritic patterns connecting the sprawling branches with a central core structure. The branched structures are formed by particles merging in the receding front. A three-dimensional lattice-gas kinetic Monte Carlo model is developed to simulate the particle self-assembling behaviour in a drying particle-laden droplet with the dewetting three-phase line. The parameter study is carried out to demonstrate the trend of the dendritic pattern formation. The various patterns are simulated by varying the chemical potentials and the interaction energies among particles, liquids, and substrates. The dendritic particle depositions are measured in three dimensions after the nanofluid droplet is completely dried. Qualitative agreement is observed between the experimental and the numerical results. Thicker branches and larger central cores are observed with an increase of particle concentrations.

Serum exosomal microRNA transcriptome profiling in subacute spinal cord injured rats.

MicroRNAs (miRNAs) are involved in a series of pathology of spinal cord injury (SCI). Although, locally expressed miRNAs have advantages in studying the pathological mechanism, they cannot be used as biomarkers. The "free circulation" miRNAs can be used as biomarkers, but they have low concentration and poor stability in body fluids. Exosomal miRNAs in body fluids have many advantages comparing with free miRNAs. Therefore, we hypothesized that the specific miRNAs in the central nervous system might be transported to the peripheral circulation and concentrated in exosomes after injury. Using next-generation sequencing, miRNA profiles in serum exosomes of sham and subactue SCI rats were analyzed. The results showed that SCI can lead to changes of serum exosomal miRNAs. These changed miRNAs and their associated signaling pathways may explain the pathological mechanism of suacute SCI. More importantly, we found some valuable serum exosomal miRNAs for diagnosis and prognosis of SCI.