Ultraviolet Photodissociation Dynamics of the 1-Methylallyl Radical.

The ultraviolet (UV) photodissociation dynamics of the 1-methylallyl (1-MA) radical were studied using the high-n Rydberg atom time-of-flight (HRTOF) technique in the wavelength region of 226-244 nm. The 1-MA radicals were produced by 193 nm photodissociation of the 3-chloro-1-butene and 1-chloro-2-butene precursor. The 1 + 1 REMPI spectrum of 1-MA agrees with the previous UV absorption spectrum in this wavelength region. Quantum chemistry calculations show that the UV absorption is mainly attributed to the 3pz Rydberg state (perpendicular to the allyl plane). The H atom photofragment yield (PFY) spectrum of 1-MA from 3-chloro-1-butene displays a broad peak around 230 nm, while that from 1-chloro-2-butene peaks at ∼236 nm. The translational energy distributions of the H atom loss product channel, P (ET)'s, show a bimodal distribution indicating two dissociation pathways in 1-MA. The major pathway is isotropic in product angular distribution with ß âˆ¼ 0 and has a low fraction of average translational energy in the total excess energy, ⟨fT⟩, in the range of 0.13-0.17; this pathway corresponds to unimolecular dissociation of 1-MA after internal conversion to form 1,3-butadiene + H. The minor pathway is anisotropic with ß âˆ¼ -0.23 and has a large ⟨fT⟩ of ∼0.62-0.72. This fast pathway suggests a direct dissociation of the methyl H atom on a repulsive excited state surface or the repulsive part of the ground state surface to form 1,3-butadiene + H. The fast/slow pathway branching ratio is in the range of 0.03-0.08.

Enhancing high-efficiency breeding and microbial microdroplet cultivation techniques for Ganoderma lucidum.

Ganoderma lucidum is known for its bioactive compounds, such as polysaccharides and triterpenoids, which are crucial in food and medicine. However, liquid fermentation encounters challenges in terms of strain differentiation and stability. In this research, we employed atmospheric room temperature plasma mutation and a microbial microdroplet culture system to identify strains with enhanced biomass and triterpenoid production. The three mutant strains, YB05, YB09, and YB18, exhibited accelerated growth rates and antagonized the initial strain G0023 more effectively than the controls. Notably, YB18 displayed the fastest growth, with a 17.25% increase in colony radius. Shake flask cultivation demonstrated that, compared with the initial strain, YB05 and YB18 had 26.33% and 17.85% greater biomass, respectively. Moreover, the triterpenoid production of YB05 and YB18 surpassed that of the control by 32.10% and 15.72%, respectively, as confirmed by colorimetric detection. Importantly, these mutant strains remained stable for five generations. This study revealed a comprehensive screening system utilizing atmospheric pressure, room temperature plasma mutation technology and microbial droplet cultivation. This innovative approach offers a promising pathway for obtaining advantageous Ganoderma strains for liquid fermentation. The methodology of atmospheric room temperature plasma mutation and microbial microdroplet culture systems is detailed for better comprehension.

Low-pressure and nascent yields of stabilized Criegee intermediates CH2OO and CH3CHOO in ozonolysis of propene.

The yields of stabilized Criegee intermediates (sCIs), both CH2OO and CH3CHOO, produced from ozonolysis of propene at low pressures (7-16 Torr) were measured indirectly using cavity ringdown spectroscopy (CRDS) and chemical titration with an excess amount of sulfur dioxide (SO2). The method of monitoring the consumption of SO2 as a scavenger and the production of secondary formaldehyde (HCHO) allows characterization of the total sCI and the stabilized CH2OO yields at low pressure and in a short residence time. Both the total sCI and the stabilized CH2OO yields in the propene ozonolysis were found to decrease with decreasing pressure. By extrapolating the 7-16 Torr measurements to the zero-pressure limit, the nascent yield of the total sCIs was determined to be 25 ± 2%. The ranges of nascent yields of stabilized CH2OO and stabilized CH3CHOO were estimated to be 20-25% and 0-5%, respectively. The branching ratios of the stabilized and high-energy CH2OO* and CH3CHOO* were also determined.

Thermal Decomposition Mechanism of Tetraethylsilane by Flash Pyrolysis Vacuum Ultraviolet Photoionization Mass Spectrometry and DFT Calculations: The Competition between ß-Hydride Elimination and Bond Homolysis.

Thermal decomposition of tetraethylsilane was investigated at temperatures up to 1330 K using flash pyrolysis vacuum ultraviolet photoionization mass spectrometry. Density functional theory and transition state theory calculations were performed to corroborate the experimental observations. Both experimental and theoretical evidence showed that the pyrolysis of tetraethylsilane was initiated by Si-C bond fission to the primary reaction products, triethylsilyl (SiEt3) and ethyl radicals. In the secondary reactions of the triethylsilyl radical, at lower temperatures, the ß-hydride elimination pathway (producing HSiEt2) was found to be more favored than its competing reaction channel, Si-C bond fission (producing :SiEt2); as the temperature further increased, the Si-C bond fission reaction became significant. Other important secondary reaction products, such as EtHSi═CH2 (m/z = 72), H2SiEt (m/z = 59), and SiH3 (m/z = 31) were identified, and their formation mechanisms were also proposed.

Mechanism of Thermal Decomposition of Hydroxyacetone: A Flash Pyrolysis Vacuum Ultraviolet Photoionization Time-of-Flight Mass Spectrometry and Density Functional Theory Study.

The thermal decomposition mechanism of hydroxyacetone from 850 to 1390 K was examined by using flash pyrolysis vacuum ultraviolet photoionization time-of-flight mass spectrometry combined with density functional theory calculation. The results showed that keto-enol tautomerisms could occur prior to the thermal decomposition of hydroxyacetone. The decomposition pathways of hydroxyacetone and its isomer, 2-hydroxypropanal were characterized. The thermal decomposition reactions started at about 950 K. The homolysis reactions related to the cleavage of the CCO-CCOH bond of hydroxyacetone and 2-hydroxypropanal, as well as CH3 loss of hydroxyacetone, dominated the initial decomposition reactions. The subsequent decompositions of the radical intermediates generated by the initial homolysis decompositions were the major secondary decomposition reactions. The formation pathways of small molecules, such as H2, CH4, H2O, and HCHO, were proposed to proceed via molecular elimination reactions facilitated by the active α-H atoms. These elimination reactions were not negligible at high temperatures above 1230 K.

Predissociation dynamics of the A2Σ+ state of SH radical: Fine-structure state distributions of the S(3PJ) products.

Photo-predissociation of rovibrational levels of SH (A2Σ+, v' = 0-6) is studied using the high-n Rydberg atom time-of-flight technique. Spin-orbit branching fractions of the S(3PJ=2,1,0) products are measured in the product translational energy distributions. The SH A2Σ+v' = 0 state predissociates predominantly via coupling to the 4Σ- repulsive state. As the vibrational level v' increases, predissociation dynamics change drastically, with all three repulsive states (4Σ-, 2Σ-, and 4Π) involved in the dissociation. Nonadiabatic interactions and quantum interferences among these dissociation pathways affect the fine-structure state distributions of the S(3PJ=2,1,0) products.

Photodissociation dynamics of the ethyl radical via the Ã2A'(3s) state: H-atom product channels and ethylene product vibrational state distribution.

The photodissociation dynamics of jet-cooled ethyl radical (C2H5) via the Ã2A'(3s) states are studied in the wavelength region of 230-260 nm using the high-n Rydberg H-atom time-of-flight (TOF) technique. The H + C2H4 product channels are reexamined using the H-atom TOF spectra and photofragment translational spectroscopy. A prompt H + C2H4(X̃1Ag) product channel is characterized by a repulsive translational energy release, anisotropic product angular distribution, and partially resolved vibrational state distribution of the C2H4(X̃1Ag) product. This fast dissociation is initiated from the 3s Rydberg state and proceeds via a H-bridged configuration directly to the H + C2H4(X̃1Ag) products. A statistical-like H + C2H4(X̃1Ag) product channel via unimolecular dissociation of the hot electronic ground-state ethyl (X̃2A') after internal conversion from the 3s Rydberg state is also examined, showing a modest translational energy release and isotropic angular distribution. An adiabatic H + excited triplet C2H4(ã3B1u) product channel (a minor channel) is identified by energy-dependent product angular distribution, showing a small translational energy release, anisotropic angular distribution, and significant internal excitation in the C2H4(ã3B1u) product. The dissociation times of the different product channels are evaluated using energy-dependent product angular distribution and pump-probe delay measurements. The prompt H + C2H4(X̃1Ag) product channel has a dissociation time scale of <10 ps, and the upper bound of the dissociation time scale of the statistical-like H + C2H4(X̃1Ag) product channel is <5 ns.

Determination and Chemotaxonomic Analysis of Lanostane Triterpenoids in the Mycelia of Ganoderma spp. Using Ultra-performance Liquid Chromatography-Tandem Mass Spectrometry (I).

A comprehensive and sensitive method combining ultra-performance liquid chromatography with tandem mass spectrometry was developed for the quantification of characteristic triterpenoids in Ganoderma mycelia. Eight ganoderic acids previously isolated from the mycelia of Ganoderma lingzhi were separated with a binary mobile phase on a reversed-phase C18 column. A triple quadrupole mass spectrometer equipped with an electrospray ionization source was used as the detector in the negative ion mode. Identification and quantitation of target ganoderic acids were accomplished using the dynamic multiple reaction monitoring mode. The developed method was validated in terms of linearity, precision, accuracy, stability, and recovery. The method was first applied to quantify the contents of eight ganoderic acids in the mycelia of G. lingzhi at different times to determine the optimum fermentation conditions. Subsequently, the distribution of triterpenoids and the contents of eight ganoderic acids in sixteen different Ganoderma species were investigated. The results indicated that UV chromatography combined with dynamic multiple reaction monitoring quantification was an effective chemotaxonomy method for Ganoderma species identification. This study also provided a helpful analytical methodology for both scientific and industrial applications in the quality control of Ganoderma triterpenoids.

Emerging Immunotherapy Approaches for Treating Prostate Cancer.

Immunotherapy has emerged as an important approach for cancer treatment, but its clinical efficacy has been limited in prostate cancer compared to other malignancies. This review summarizes key immunotherapy strategies under evaluation for prostate cancer, including immune checkpoint inhibitors, bispecific T cell-engaging antibodies, chimeric antigen receptor (CAR) T cells, therapeutic vaccines, and cytokines. For each modality, the rationale stemming from preclinical studies is discussed along with outcomes from completed clinical trials and strategies to improve clinical efficacy that are being tested in ongoing clinical trials. Imperative endeavors include biomarker discovery for patient selection, deciphering resistance mechanisms, refining cellular therapies such as CAR T cells, and early-stage intervention were reviewed. These ongoing efforts instill optimism that immunotherapy may eventually deliver significant clinical benefits and expand treatment options for patients with advanced prostate cancer.

Detectable Lipidomes and Metabolomes by Different Plasma Exosome Isolation Methods in Healthy Controls and Patients with Advanced Prostate and Lung Cancer.

Circulating exosomes in the blood are promising tools for biomarker discovery in cancer. Due to their heterogeneity, different isolation methods may enrich distinct exosome cargos generating different omic profiles. In this study, we evaluated the effects of plasma exosome isolation methods on detectable multi-omic profiles in patients with non-small cell lung cancer (NSCLC), castration-resistant prostate cancer (CRPC), and healthy controls, and developed an algorithm to quantify exosome enrichment. Plasma exosomes were isolated from CRPC (n = 10), NSCLC (n = 14), and healthy controls (n = 10) using three different methods: size exclusion chromatography (SEC), lectin binding, and T-cell immunoglobulin domain and mucin domain-containing protein 4 (TIM4) binding. Molecular profiles were determined by mass spectrometry of extracted exosome fractions. Enrichment analysis of uniquely detected molecules was performed for each method with MetaboAnalyst. The exosome enrichment index (EEI) scores methods based on top differential molecules between patient groups. The lipidomic analysis detected 949 lipids using exosomes from SEC, followed by 246 from lectin binding and 226 from TIM4 binding. The detectable metabolites showed SEC identifying 191 while lectin binding and TIM4 binding identified 100 and 107, respectively. When comparing uniquely detected molecules, different methods showed preferential enrichment of different sets of molecules with SEC enriching the greatest diversity. Compared to controls, SEC identified 28 lipids showing significant difference in NSCLC, while only 1 metabolite in NSCLC and 5 metabolites in CRPC were considered statistically significant (FDR < 0.1). Neither lectin-binding- nor TIM4-binding-derived exosome lipids or metabolites demonstrated significant differences between patient groups. We observed the highest EEI from SEC in lipids (NSCLC: 871.33) which was also noted in metabolites. These results support that the size exclusion method of exosome extraction implemented by SBI captures more heterogeneous exosome populations. In contrast, lectin-binding and TIM4-binding methods bind surface glycans or phosphatidylserine moieties of the exosomes. Overall, these findings suggest that specific isolation methods select subpopulations which may significantly impact cancer biomarker discovery.

Multiple Fingerprint-Activity Relationship Assessment of Immunomodulatory Polysaccharides from Ganoderma lucidum Based on Chemometric Methods.

Polysaccharides with molecular weights ranging from 1.75 × 103 to 1.14 × 104 g/mol were obtained from the fruit bodies of Ganoderma lucidum. The multiple fingerprints and macrophage immunostimulatory activity of these fractions were analyzed as well as the fingerprint-activity relationship. The correlation analysis of molecular weight and immune activity demonstrated that polysaccharides with molecular weights of 4.27 × 103~5.27 × 103 and 1 × 104~1.14 × 104 g/mol were the main active fractions. Moreover, the results showed that galactose, mannose, and glucuronic acid were positively related to immunostimulatory activity. Additionally, partial least-squares regression and grey correlation degree analyses indicated that three peaks (P2, P3, P8) in the oligosaccharide fragment fingerprint significantly affected the immune activity of the polysaccharides. Hence, these ingredients associated with activity could be considered as markers to assess Ganoderma lucidum polysaccharides and their related products, and the study also provides a reference for research on the spectrum-effect relationship of polysaccharides in the future.

The key technologies of Ganoderma lucidum liquid spawn preparation and scale expansion.

Ganoderma lucidum possesses a variety of valuable pharmacological activities, and it has long been used to prevent and treat various human diseases. Up to now, far too little attention has been paid to the liquid spawn of G. lucidum, and the development of the G. lucidum industry is constrained by them. This work aimed to study the key technologies and scale-up preparation of G. lucidum liquid spawn, to achieve large-scale preparation of liquid spawn and solve the problem of unstable quality of G. lucidum. The plate culture, primary shake flask culture, shake flask preparation, and fermentor preparation of G. lucidum liquid spawn were explored in the process of liquid fermentation. The results showed that plate broth volume significantly affected mycelial growth rate. Biomass in the primary shake flask culture is significantly influenced by the picking position of plate mycelium. An artificial neural network coupled with a genetic algorithm was used for carbon and nitrogen sources concentration optimization to increase biomass and substrate utilization. The optimized parameter combination is as follows: glucose, 14.5 g L-1; yeast extract powder, 8.5 g L-1. Under this condition, the biomass (9.82 g L-1) and biomass on reducing sugar (0.79 g g-1) increased by 18.03% and 27.41% compared to the control, respectively. The metabolic activity of liquid spawn prepared by different fermentation scales was diverse, and the liquid spawn prepared by the fermentor has better activity. Conceivably, the liquid spawn process can more conducive be applied to large-scale industrial production.

Unimolecular dissociation dynamics of electronically excited HCO(Ã2A''): rotational control of nonadiabatic decay.

The photoinduced unimolecular decay of the electronically excited HCO(Ã2A'') is investigated in a combined experimental-theoretical study. The molecule is excited to the (1, n2, 0) combination bands, which decay via Renner-Teller coupling to the ground electronic state. The rovibrational state distribution of the CO fragment was measured via the high-n Rydberg H-atom time-of-flight method and calculated using a wave packet method on an accurate set of potential energy surfaces. It is shown that the non-adiabatic decay rate is strongly modulated by the HCO rotational angular momentum, which leaves unique signatures in the product state distribution. The experimentally observed bimodal rotational distribution of the dominant CO(v = 0) fragment is likely due to decay of different vibronic states populated by the excitation and modulated by the excited state lifetime, which is in turn controlled by the parent rotational quantum number.

Yttrium-90 Radioembolization for Liver-Dominant Metastatic Prostate Cancer: A Case Series.

Transarterial radioembolization (TARE) with yttrium-90 glass microspheres is widely used to treat primary and secondary malignancies in the liver. However, the safety and efficacy of TARE in patients with liver-dominant metastatic castration-resistant prostate cancer (mCRPC) is unknown. A proof-of-concept, retrospective analysis of 7 consecutive patients with liver-dominant mCRPC who were treated with TARE was performed. The median overall survival was 27.2, 32.1, and 108.1 months from the time of TARE, the diagnosis of liver metastases, and initial cancer diagnosis, respectively. The median liver progression-free survival was 7.3 months. No grade 3 or higher adverse effects were noted. TARE was found to be a safe and effective tool for treating patients with liver-dominant mCRPC in this limited cohort.

Two-photon dissociation dynamics of the mercapto radical.

Two-photon dissociation dynamics of the SH/SD radicals are investigated using the high-n Rydberg atom time-of-flight (HRTOF) technique. The H/D(2S) + S(1D) and H/D(2S) + S(1S) products are observed in the dissociation of the SH/SD radicals on the 22Π and B2Σ+ repulsive states, from sequential two-photon excitation via the A2Σ+ (v' = 0, J' = 0.5-2.5) state. The angular distributions of both H/D(2S) + S(1D) and H/D(2S) + S(1S) product channels are anisotropic. The anisotropy parameter (ß) of the H(2S) + S(1D) products is ∼-0.8 ± 0.1 (-0.9 ± 0.05 for SD), and that of the H(2S) + S(1S) products is ∼1.3 ± 0.3 (1.2 for SD). The anisotropic angular distributions indicate that the SH/SD radicals promptly dissociate on the repulsive 22Π and B2Σ+ potential energy curves (PECs) along with some non-adiabatic crossings, leading to the H/D(2S) + S(1D) and H/D(2S) + S(1S) products, respectively. The bond dissociation energy of the ground-state X2Π3/2 SH/SD to the ground-state H/D(2S) + S(3P2) products is measured to be D0(S-H) = 29 253 ± 20 cm-1 and D0(S-D) = 29 650 ± 20 cm-1, respectively. The dissociation energy of the A2Σ+ state SH/SD to the H/D(2S) + S(1D) products is derived to be D0[S-H(A)] = 7659 ± 20 cm-1 and D0[S-D(A)] = 7940 ± 20 cm-1.

A Mechanistic Study of Thermal Decomposition of 1,1,2,2-Tetramethyldisilane Using Vacuum Ultraviolet Photoionization Time-of-Flight Mass Spectrometry.

Thermal decomposition of 1,1,2,2-tetramethyldisilane was performed by flash pyrolysis in a SiC microreactor in the temperature range from 295 to 1340 K, followed by molecular beam sampling and vacuum ultraviolet photoionization mass spectrometry analysis. Density functional theory investigations on the energetics of reactants, intermediates, and products were carried out to support the experimental observations. Energetics for 1,1,2,2-tetramethyldisilane initiation decomposition reactions and important secondary reactions were calculated. Dimethylsilane, dimethylsilyl radicals, dimethylsilylene, trimethylsilane, and tetramethyldisilene were determined as the primary reaction products in the initiation thermal decompositions of 1,1,2,2-tetramethyldisilane. Further decomposition reactions of tetramethyldisilene, such as production of dimethylsilene (m/z = 72) and eventually SiC3H4 (m/z = 68) fragments, were examined. Other products from secondary reactions of dimethylsilane and dimethylsilylene such as SiC2H2-6 and SiCH0-4 were also observed. The comprehensive pyrolysis mechanism of 1,1,2,2-tetramethyldisilane was proposed.

Thermal and Catalytic Decomposition of 2-Hydroxyethylhydrazine and 2-Hydroxyethylhydrazinium Nitrate Ionic Liquid.

To develop chemical kinetics models for the combustion of ionic liquid-based monopropellants, identification of the elementary steps in the thermal and catalytic decomposition of components such as 2-hydroxyethylhydrazinium nitrate (HEHN) is needed but is currently not well understood. The first decomposition step in protic ionic liquids such as HEHN is typically the proton transfer from the cation to the anion, resulting in the formation of 2-hydroxyethylhydrazine (HEH) and HNO3. In the first part of this investigation, the high-temperature thermal decomposition of HEH is probed with flash pyrolysis (<1400 K) and vacuum ultraviolet (10.45 eV) photoionization time-of-flight mass spectrometry (VUV-PI-TOFMS). Next, the investigation into the thermal and catalytic decomposition of HEHN includes two mass spectrometric techniques: (1) tunable VUV-PI-TOFMS (7.4-15 eV) and (2) ambient ionization mass spectrometry utilizing both plasma and laser ionization techniques whereby HEHN is introduced onto a heated inert or iridium catalytic surface and the products are probed. The products can be identified by their masses, their ionization energies, and their collision-induced fragmentation patterns. Formation of product species indicates that catalytic surface recombination is an important reaction process in the decomposition mechanism of HEHN. The products and their possible elementary reaction mechanisms are discussed.

Vibrational energy levels and predissociation lifetimes of the A2Σ+ state of SH/SD radicals by photodissociation spectroscopy.

Photo-predissociation of SH and SD radicals in the A2Σ+ state is investigated using the high-n Rydberg atom time-of-flight technique. By measuring the photoproduct translational energy distributions as a function of excitation wavelength, contributions from overlapping A2Σ+ (v') ← X2Π (v″) transitions can be separated, and the H/D + S(3PJ) photofragment yield (PFY) spectra are obtained across various rovibrational levels (SH v' = 0-7 and SD v' = 0-8) of the A2Σ+ ← X2Π bands. The upper A2Σ+ state vibrational levels v' = 5-7 of SH and v' = 3-8 of SD are determined for the first time. The PFY spectra are analyzed with the simulation program PGOPHER [C. M. Western, J. Quant. Spectrosc. Radiat. Transfer 186, 221 (2016)], which gives vibrational origins and linewidths of the rovibrational levels of the A2Σ+ state. The linewidths (≥1.5 cm-1) of the SH A2Σ+ v' = 3-7 and SD A2Σ+ v' = 2-8 states are characterized for the first time in this work, demonstrating that these levels undergo rapid predissociation with lifetimes on the order of picosecond. The lifetimes of the SD A2Σ+ v' = 0, N' = 1 and 2 levels are determined to be 247 ± 50 ns and 176 ± 60 ns by pump-probe delay measurements, respectively. The experimentally measured lifetimes are in reasonable agreement with the theoretical predictions.

Integrative Analysis of Selected Metabolites and the Fungal Transcriptome during the Developmental Cycle of Ganoderma lucidum Strain G0119 Correlates Lignocellulose Degradation with Carbohydrate and Triterpenoid Metabolism.

To systemically understand the biosynthetic pathways of bioactive substances, including triterpenoids and polysaccharides, in Ganoderma lucidum, the correlation between substrate degradation and carbohydrate and triterpenoid metabolism during growth was analyzed by combining changes in metabolite content and changes in related enzyme expression in G. lucidum over 5 growth phases. Changes in low-polarity triterpenoid content were correlated with changes in glucose and mannitol contents in fruiting bodies. Additionally, changes in medium-polarity triterpenoid content were correlated with changes in the lignocellulose content of the substrate and with the glucose, trehalose, and mannitol contents of fruiting bodies. Weighted gene coexpression network analysis (WGCNA) indicated that changes in trehalose and polyol contents were related to carbohydrate catabolism and polysaccharide synthesis. Changes in triterpenoid content were related to expression of the carbohydrate catabolic enzymes laccase, cellulase, hemicellulase, and polysaccharide synthase and to the expression of several cytochrome P450 monooxygenases (CYPs). It was concluded that the products of cellulose and hemicellulose degradation participate in polyol, trehalose, and polysaccharide synthesis during initial fruiting body formation. These carbohydrates accumulate in the early phase of fruiting body formation and are utilized when the fruiting bodies mature and a large number of spores are ejected. An increase in carbohydrate metabolism provides additional precursors for the synthesis of triterpenoids. IMPORTANCE Most studies of G. lucidum have focused on its medicinal function and on the mechanism of its activity, whereas the physiological metabolism and synthesis of bioactive substances during the growth of this species have been less studied. Therefore, theoretical guidance for cultivation methods to increase the production of bioactive compounds remains lacking. This study integrated changes in the lignocellulose, carbohydrate, and triterpenoid contents of G. lucidum with enzyme expression from transcriptomics data using WGCNA. The findings helped us better understand the connections between substrate utilization and the synthesis of polysaccharides and triterpenoids during the cultivation cycle of G. lucidum. The results of WGCNA suggest that the synthesis of triterpenoids can be enhanced not only through regulating the expression of enzymes in the triterpenoid pathway, but also through regulating carbohydrate metabolism and substrate degradation. This study provides a potential approach and identifies enzymes that can be targeted to regulate lignocellulose degradation and accelerate the accumulation of bioactive substances by regulating substrate degradation in G. lucidum.

Pathological Downstaging and Survival Outcomes Associated with Neoadjuvant Chemotherapy for Variant Histology Muscle Invasive Bladder Cancer.

PURPOSE: Patients with muscle invasive bladder cancer (MIBC) of variant histology have a poor prognosis. It is unclear if neoadjuvant chemotherapy prior to radical cystectomy is associated with pathological downstaging or improved overall survival (OS) for patients with variant histology. Our objective was to assess for associations between receipt of neoadjuvant chemotherapy, pathological downstaging and OS for patients with variant histology MIBC. MATERIALS AND METHODS: Patients were identified in the National Cancer Database from 2004 to 2017 with MIBC, without metastases, who underwent radical cystectomy. Patients were stratified by histological subgroup, and receipt or nonreceipt of neoadjuvant chemotherapy. Pathological downstaging was defined as pT0N0 or pT ≤1N0, and OS from the time of diagnosis to date of death or censoring at last followup. Multivariable logistic regression analysis determined associations between neoadjuvant chemotherapy and pathological downstaging. Multivariable Cox regression analysis determined associations between neoadjuvant chemotherapy and OS. RESULTS: A total of 31,218 patients were included in the final study population (urothelial carcinoma [UC]: 27,779; sarcomatoid UC: 501; micropapillary UC: 418; squamous cell carcinoma: 1,141; neuroendocrine carcinoma: 629; adenocarcinoma: 750). Neoadjuvant chemotherapy was associated with pathological downstaging to pT0N0 in all histological subgroups (UC: OR 5.1 [4.6-5.6]; sarcomatoid UC: OR 13.8 [5.5-39.0]; micropapillary UC: OR 9.7 [2.8-46.8]; squamous cell carcinoma: OR 7.4 [2.1-24.5]; neuroendocrine: OR 4.7 [2.6-9.2]; adenocarcinoma: OR 23.3 [8.0-74.2]). Neoadjuvant chemotherapy was associated with improved OS for UC (HR 0.8 [0.77-0.84]), sarcomatoid UC (HR 0.64 [0.44-0.91]) and neuroendocrine carcinoma (HR 0.55 [0.43-0.70]). CONCLUSIONS: Neoadjuvant chemotherapy was associated with pathological downstaging for all MIBC histological variants, with improved OS for patients with UC, sarcomatoid variant UC and neuroendocrine carcinoma.