A comparative study of mono-exponential and advanced diffusion-weighted imaging in differentiating stage IA endometrial carcinoma from benign endometrial lesions.

PURPOSE: The purpose of the current investigation is to compare the efficacy of different diffusion models and diffusion kurtosis imaging (DKI) in differentiating stage IA endometrial carcinoma (IAEC) from benign endometrial lesions (BELs). METHODS: Patients with IAEC, endometrial hyperplasia (EH), or a thickened endometrium confirmed between May 2016 and August 2022 were retrospectively enrolled. All of the patients underwent a preoperative pelvic magnetic resonance imaging (MRI) examination. The apparent diffusion coefficient (ADC) from the mono-exponential model, pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) from the bi-exponential model, distributed diffusion coefficient (DDC), water molecular diffusion heterogeneity index from the stretched-exponential model, diffusion coefficient (Dk) and diffusion kurtosis (K) from the DKI model were calculated. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficiency. RESULTS: A total of 90 patients with IAEC and 91 patients with BELs were enrolled. The values of ADC, D, DDC and Dk were significantly lower and D* and K were significantly higher in cases of IAEC (p < 0.05). Multivariate analysis showed that K was the only predictor. The area under the ROC curve of K was 0.864, significantly higher compared with the ADC (0.601), D (0.811), D* (0.638), DDC (0.743) and Dk (0.675). The sensitivity, specificity and accuracy of K were 78.89%, 85.71% and 80.66%, respectively. CONCLUSION: Advanced diffusion-weighted imaging models have good performance for differentiating IAEC from EH and endometrial thickening. Among all of the diffusion parameters, K showed the best performance and was the only independent predictor. Diffusion kurtosis imaging was defined as the most valuable model in the current context.

Enlargement of the knowledge of Cortinarius section Anomali (Agaricales, Basidiomycota): introducing three new species from China.

Cortinarius is a globally distributed agaricoid genus that has been well studied in Europe and America with over 1,000 described species. However, as part of an ongoing effort to investigate the diversity of Cortinarius section Anomali in China, the resource investigation and classification research are still limited, and the species diversity has not been clarified by far. During the re-examination of the Chinese Cortinarius specimens, C. cinnamomeolilacinus, C. subclackamasensis, and C. tropicus, belonging to the sect. Anomali, were described in China as new to science based on morphological examination and phylogenetic analysis. The three new species are described and illustrated in detail according to the Chinese materials. The phylogenetic analysis based on internal transcribed spacer sequences confirmed the placement of the three species in the Cortinarius sect. Anomali clade. Phylogenetically related and morphologically similar species to these three new species are discussed.

Four cases of reported adverse effects from black boletoi, Anthracoporus nigropurpureus (Boletaceae) mushroom ingestion.

In southwestern China, wild boletes are generally considered as safe and tasty edible mushrooms. However, in fact, significant adverse effects after ingestion of boletes is commonly reported in this region. In June 2022, four cases occurred in central and southwestern of China. In these case series, five adults and one child ingested wild boletoi mushrooms known locally as "Yanyoujun" (). This study carried out a detailed epidemiological investigation and mushroom identification. Based on morphological and phylogenetic analysis, the suspected mushrooms were identified as Anthracoporus nigropurpureus (Boletaceae). All five adult victims reported dizziness and blurred vision. Some of them also reported different symptoms, such as muscle weakness, red eyes, headache, muscle cramps, even tremors in the extremities. Reportedly, the symptoms began to subside about 4 to 8 h after ingestion. Among six victims, the child was asymptomatic possibly because a small amount of mushroom was ingested. This possible poisoning appears to be a self-limited illness with a short latency and a relatively short duration. Unfortunately, laboratory investigations of the victims were not performed. Further observations and formal medical examination of victims are required in the future. It is the first detailed report of possible poisoning the genus Anthracoporus.

Taxonomy and Phylogeny of Corticioid Fungi in Auriculariaceae (Auriculariales, Basidiomycota): A New Genus, Five New Species and Four New Combinations.

The Auriculariaceae accounts for most of the species in the Auriculariales, and all species in the family are wood-decaying fungi with gelatinous, crustaceous, or woody basidiomes. Many new taxa were published recently, but the taxonomy and phylogeny of the corticioid species in the Auriculariaceae are far from resolved. We undertook a comprehensive taxonomic and phylogenetic study of the family with emphasis on corticioid specimens collected from East and Southeast Asia. Phylogenetic analyses on concatenated ITS and 28S rDNA sequences of representative taxa of the Auriculariaceae and the genera Eichleriella and Heteroradulum were carried out that resolved five new lineages. Heterocorticium gen. nov. is established for two species with resupinate coriaceous basidiomes with smooth, pigmented hymenophores. Five new species, H. bambusicola (generic type), H. latisporum, Eichleriella alpina, E. bambusicola, and Heteroradulum maolanense, are described and illustrated. In addition, Heterochaete delicata, H. discolor, and H. sinensis are transferred to Eichleriella, whereas H. roseola is regarded as a synonym of Kneiffia discolor (= H. discolor). Eichleriella aculeobasidiata is treated as a synonym of Heterochaete sinensis (= E. sinensis). Heterochaete mussooriensis is transferred to Heteroradulum with Heteroradulum semis as a heterotypic synonym. The present study contributes to the understanding of species diversity, taxonomy, and phylogeny of corticioid fungi in Asia.

Morphology and phylogeny identify two new species and one new subspecies of Podoscypha from Yunnan Province, Southwest China.

In this study, Podoscypha was taxonomically and phylogenetically evaluated. In total, five specimens collected from the tropical areas of Yunnan Province in Southwest China were studied. In combination with morphological observations and phylogenetic analyses based on ITS and LSU loci, two new species and one new subspecies, Podoscypha subinvoluta, P. tropica, and P. petalodes subsp. cystidiata, respectively, were discovered. The illustrated descriptions of the new species and subspecies are provided. Moreover, the main morphological differences between related species are discussed.

Toxin screening of Pseudosperma umbrinellum (Agaricals, Basidiomycota): First report of phalloidin in Inocybaceae mushroom.

Pseudosperma species are widely distributed worldwide. Many of them cause poisoning incidents every year, and the toxin responsible for poisoning is muscarine, which could stimulate the parasympathetic nervous system. This study established a method using multiwalled carbon nanotube purification and liquid chromatography-tandem mass spectrometry for the targeted screening of mushroom toxins (muscarine, isoxazole derivatives, tryptamine alkaloids, three amatoxins and three phallotoxins) from Pseudosperma umbrinellum, a common poisonous mushroom distributed in north and northwestern China. Surprisingly, in addition to muscarine, phalloidin was also detected in P. umbrinellum, and the contents were 3022.2 ± 604.4 to 4002.3 ± 804.6 mg/kg (k = 2; p = 95%) muscarine and 5.9 ± 1.2 to 9.3 ± 1.8 mg/kg (k = 2; p = 95%) phalloidin.

A New Muscarine-Containing Inosperma (Inocybaceae, Agaricales) Species Discovered From One Poisoning Incident Occurring in Tropical China.

Currently, mushroom poisoning still poses a huge problem to humans' health and life globally. Poisoning incidents caused by Inosperma spp. were reported continuously in tropical China in recent years. In this study, a new poisonous Inosperma species, discovered from a poisoning incident, was described in tropical China based on morphological, molecular, and toxin detection evidence; detailed descriptions, photographs, and comparisons to closely related species were provided. For qualitative analysis, through targeted screening using ultra-high liquid chromatography triple quadrupole mass spectrometry (UPLC-MS/MS), the new species contains muscarine and no other toxins (two isoxazole derivatives, two tryptamine alkaloids, three amatoxins, and three phallotoxins). For quantitative analysis, muscarine contents in the pileus and the stipe were 2.08 ± 0.05 and 6.53 ± 1.88 g/kg, respectively.

 Pseudospermaarenarium (Inocybaceae), a new poisonous species from Eurasia, based on morphological, ecological, molecular and biochemical evidence.

In this study, Pseudospermaarenarium is proposed as a new species, based on morphological, ecological, molecular and biochemical evidence. The new species grows on sandy ground under Populus and Pinussylvestris in north-western China and northern Europe, respectively. It is characterised by the combination of the robust habit, nearly glabrous pileus, large cylindrical basidiospores, thin-walled cheilocystidia and ecological associations with Populusalba × P.berolinensis and Pinussylvestris and unique phylogenetic placement. Additionally, a comprehensive toxin determination of the new species using ultra-high performance liquid chromatography-tandem mass spectrometry was conducted. Results showed that it was a muscarine-positive species. The content were approximately five times higher in the pilei [4012.2 ± 803.1-4302.3 ± 863.2 mg/kg (k = 2, p = 95%)] than in the stipes [850.4 ± 171.1-929.1 ± 184.2 mg/kg (k = 2, p = 95%)], demonstrating the severity of mushroom poisoning when patients consumed different parts of the poisonous mushroom. Amatoxins, phallotoxins, ibotenic acid, muscimol, psilocybin and psilocin were not detected.

Mushroom poisoning from Inocybe serotina: A case report from Ningxia, northwest China with exact species identification and muscarine detection.

Mushroom poisoning is a serious food safety issue in China. However, there is insufficient information on many poisoning incidents, including mushroom species and their clinical manifestations, diagnosis, treatments and toxins. Detailed epidemiological investigation was conducted after the occurrence of a mushroom poisoning incident resulting in typical muscarinic syndrome in Ningxia, China. The suspected mushroom species was identified based on morphological and phylogenetic analyses. Muscarine was detected using ultrahigh-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). On September 2, 2019, two patients exhibited typical muscarinic syndrome after consuming wild mushrooms. The clinical manifestations included chills, sweating, salivation and diarrhoea; the incubation period was approximately 2 h. Treatments, including anti-inflammatory, detoxification and nutritional support, were remedial. Full recovery ensued within 24 h. The specimen was identified as Inocybe serotina, and its muscarine content was 324.0 ± 62.4 mg/kg (k = 2, p = 95%). Two patients were poisoned via stimulation of their parasympathetic nervous system due to mistaken consumption of muscarine-containing I. serotina. They fully recovered with supportive treatments. To our knowledge, this is the first case report of I. serotina poisoning worldwide and is the first record of this species in China. Further, a method for muscarine detection was established using UPLC-MS/MS.

Active Ingredients and Anti-Arthritic Mechanisms of Ba-Wei-Long-Zuan Granule Revealed by 1 H-NMR-Based Metabolomics Combined with Network Pharmacology Analysis.

Ba-Wei-Long-Zuan granule (BWLZ) is a traditional herbal preparation. It has been widely used for the treatment of rheumatoid arthritis (RA). However, its active ingredients and mechanisms of action are still unclear. The present study aims to reveal the active compounds and anti-arthritic mechanisms of BWLZ against collagen-induced arthritis (CIA) by using 1 H-NMR-based metabolomics, molecular docking and network pharmacology methods. After 30 days of administration, BWLZ could effectively improve the metabolic disorders in CIA rats. The anti-arthritic effect of BWLZ was related to its restoration of 16 disturbed serum metabolites. Molecular docking and network analysis showed that 20 compounds present in BWLZ could act on multiple targets. Among them, coclaurine and hesperidin showed the highest hit rates for target proteins related to both metabolic regulation and RA, indicating that these two compounds might be potential active ingredients of BWLZ. Moreover, pathway enrichment analysis suggested that the anti-arthritic mechanisms of BWLZ might be attributed to its network regulation of several biological processes, such as steroid hormone biosynthesis, mTOR signaling pathway, alanine, aspartate and glutamate metabolism, and synthesis and degradation of ketone bodies. These results provide further evidence for the anti-arthritic properties of BWLZ and are beneficial for its quality control and clinical application. The potential targets and biological processes found in this study may provide valuable information for further studying the molecular mechanisms of BWLZ against RA. In addition, our work provides new insights for revealing the active ingredients and regulatory mechanisms of complex herbal preparations.

A case report of acute renal failure caused by Amanita neoovoidea poisoning in Anhui Province, eastern China.

Amanita neoovoidea (genus Amanita Pers.) poisoning leads to acute renal failure. Here, we present seven case reports of acute renal failure with acute hepatic failure due to ingestion of A. neoovoidea. Clinical manifestations included gastrointestinal symptoms 1-72 h after ingestion; elevation of renal parameters and blood uric acid, blood urea nitrogen, and creatinine levels; a few abnormal hepatic parameters, primarily albumin decrease and alanine aminotransferase increase; and elevation of zymogram parameters such as cholinesterase and lactate dehydrogenase. To determine whether the hepatic/renal lesions were caused by amanitins, we analyzed the blood and urine samples of patients and specimens of poisonous mushrooms. Morphological and molecular biological analyses indicated that the mushroom was A. neoovoidea. However, no amatoxins and phallotoxins were detected in its basidiomata.

Lnc-TCL6 is a potential biomarker for early diagnosis and grade in liver-cirrhosis patients.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been applied as biomarkers in many diseases. However, scarce biomarkers are available in single lncRNA differential expression associated with different clinical stages of liver cirrhosis (LC). The aim of the study is to identify some lncRNAs that can serve as non-invasive sensitive biomarkers for early diagnosis and grade of LC. METHODS: Blood lncRNA expression was evaluated in three independent cohorts with 305 participants including healthy controls, hepatitis B virus (HBV) carriers, and patients with chronic hepatitis B (CHB) or LC. First, candidate lncRNAs were screened by CapitalBiotech microarray to diagnose cirrhosis. Quantitative reverse-transcriptase polymerase chain reaction was then used to investigate the expression of selected lncRNAs in the whole group of cirrhosis and different Child-Pugh classes. Ultimately, the diagnostic accuracy of the promising biomarker was examined and validated via Mann-Whitney test and receiver-operating characteristics analysis. RESULTS: Lnc-TCL6 was identified as a sensitive biomarker for early diagnosis of LC (Child-Pugh A) compared with healthy controls (area under the ROC curve [AUC] = 0.636), HBV carriers (AUC = 0.671), and CHB patients (AUC = 0.672). Furthermore, lnc-TCL6 showed a favourable capacity in discriminating among different Child-Pugh classes (AUC: 0.711-0.837). Compared with healthy controls, HBV carriers, and CHB patients, the expression of lnc-TCL6 was obviously up-regulated in Child-Pugh A patients and, conversely, significantly down-regulated in Child-Pugh C patients. CONCLUSIONS: Lnc-TCL6 is a novel potential biomarker for early diagnosis of LC and is a possible predictor of disease progression.

Chemical Composition of Bawei Longzuan Granule and Its Anti-Arthritic Activity on Collagen-Induced Arthritis in Rats by Inhibiting Inflammatory Responses.

Bawei Longzuan granule (BLG) is a representative Zhuang medicine preparation. The present work aims to characterize the chemical constituents of BLG and evaluate its anti-arthritic activity. The major chemical constituents of BLG were tentatively identified by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), which revealed the presence of some alkaloids (e. g., magnoflorine, sinomenine and nitidine) and flavonoids (e. g., hesperidin, diosmin and sinensetin) that may be partly responsible for the anti-arthritic effect of BLG. In addition, the collagen-induced arthritis (CIA) model in rats was induced by intradermal injection of bovine collagen-II in complete Freund's adjuvant at the base of tail. The CIA rats received oral administration of BLG (1.25, 2.5 and 5 g/kg) for 30 days. Then, various indicators were determined to evaluate its anti-arthritic activity, including paw swelling, arthritic score, body weight, knee joint pathology, thymus index and spleen index. Additionally, the serum levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1ß, IL-6, IL-4 and IL-10 were measured to determine the underlying mechanisms. The results showed that BLG efficiently ameliorated the severity of arthritis in CIA rats by decreasing paw swelling and arthritis score and improving the histological lesions of knee joint. Moreover, the serum levels of several pro-inflammatory cytokines (i. e., IL-1ß, TNF-α, IL-6 and IFN-γ) were downregulated, whereas two anti-inflammatory factors (i. e., IL-4 and IL-10) were upregulated after BLG administration. These results indicated that BLG possessed promising therapeutic effect on collagen-induced arthritis by inhibiting inflammatory responses. BLG can be used as a complementary or alternative traditional medicine to treat rheumatoid arthritis.

A case study of Lepiota brunneoincarnata poisoning with endoscopic nasobiliary drainage in Shandong, China.

The most frequently reported fatal Lepiota ingestions are due to L. brunneoincarnata. We present a case of L. brunneoincarnata poisoning with endoscopic nasobiliary drainage known to be the first in China. The patient suffered gastrointestinal symptoms 9 h post ingestion of mushrooms. The patient was hospitalized 4 days after eating the mushrooms with jaundice. The peak ALT, AST, APTT, TBIL and DBIL values of the patient were as follow: ALT, 2980 U/L (day 4 post ingestion); AST, 1910 U/L (day 4 post ingestion); APTT, 92.8 seconds (day 8 post ingestion), TBIL, 136 µmol/L (day 10 post ingestion), DBIL 74 µmol/L (day 10 post ingestion). UPLC-ESI-MS/MS was used to detect the peptide toxins in the mushroom and biological samples from the patient. We calculated that the patient may have ingested a total of 29.05 mg amatoxin from 300 g mushrooms, consisting of 19.91 mg α-amanitin, 9.1 mg ß-amanitin, and 0.044 mg γ-amanitin. Amatoxins could be detected in bile even on day 6 after ingestion of L. brunneoincarnata. With rehydration, endoscopic nasobiliary drainage and intravenous infusion of Legalon SIL, the patient recovered after serious hepatotoxicity developed.

Effect of Biliary Drainage on the Toxicity and Toxicokinetics of Amanita exitialis in Beagles.

Amatoxin poisoning induces delayed-onset acute liver failure, which are responsible for more than 90% of deaths in mushroom poisoning. It has been postulated from animal and human studies that biliary drainage interrupting enterohepatic amatoxin circulation may affect amatoxin poisoning. Dogs were randomly divided into four groups of six animals each. In 20 mg/kg and 60 mg/kg with biliary drainage groups, after accepting bile drainage operation, beagles were fed Amanita exitialis powder (20 or 60 mg/kg) in starch capsules. In control and bile drainage groups, the beagle dogs were fed with empty capsules. They were assessed for toxicity signs, biochemical and pathological changes, and peptide toxins in plasma, urine and bile. The data were directly compared with those from our published studies on Amanita exitialis-exposed beagles without biliary drainage. Amatoxins were rapidly absorbed and eliminated from plasma after Amanita exitialis ingestion. Amatoxins in 0⁻1-day urine accounted for more than 90% of the total urine excretion, and amatoxins in bile accounted for less than 20% of the total urine and bile excretion. The dogs with biliary drainage showed less severe toxicity signs and biochemical and pathological changes and much lower internal exposure than dogs without biliary drainage. Biliary drainage caused a more than 70% reduction in intestinal amatoxin absorption and could reduce amatoxin absorption from the gastrointestinal tract.

[Fecal Tibetan medicines].

Fecal Tibetan medicines have a long history of application in China, with a good clinical efficacy. In order to promote the development and modernization of these medicines, we consulted ancient and modern Tibetan medicine literatures to collect and summarize the names, original species, natures, flavor, functions and processing methods of fecal Tibetan medicines. A total of 35 fecal Tibetan medicines were collected, such as Jiufen, Heibingpian, Langfen, Mafen, Goufen, Gezifen. The most commonly used medicines were Jiufen and Heibingpian. Both were mainly used for the treatment of indigestion, food abdominal distension, gastric ulcer, and other gastrointestinal diseases. At present, there are only a few studies on the active ingredients, pharmacodynamics and mechanism of action of these medicines. Therefore, further study shall be conducted. The regulation of gut microbiota may be a new way to evaluate the effectiveness of fecal Tibetan medicines and their mechanism of action.

Natural Medicines Used in the Traditional Tibetan Medical System for the Treatment of Liver Diseases.

Liver disease is one of the most risk factors threatening human health. It is of great significance to find drugs that can treat liver diseases, especially for acute and chronic hepatitis, non-alcoholic fatty liver disease, and liver cancer. The search for drugs with good efficacy from traditional natural medicines has attracted more and more attention. Tibetan medicine, one of the China's traditional medical systems, has been widely used by the Tibetan people for the prevention and treatment of liver diseases for hundreds of years. The present paper summarized the natural Tibetan medicines that have been used in Tibetan traditional system of medicine to treat liver diseases by bibliographic investigation of 22 Tibetan medicine monographs and drug standards. One hundred and ninety three species including 181 plants, 7 animals, and 5 minerals were found to treat liver diseases in traditional Tibetan medicine system. The most frequently used species are Carthamus tinctorius, Brag-zhun, Swertia chirayita, Swertia mussotii, Halenia elliptica, Herpetospermum pedunculosum, and Phyllanthus emblica. Their names, families, medicinal parts, traditional uses, phytochemicals information, and pharmacological activities were described in detail. These natural medicines might be a valuable gift from the old Tibetan medicine to the world, and would be potential drug candidates for the treatment of liver diseases. Further studies are needed to prove their medicinal values in liver diseases treatment, identify bioactive compounds, elucidate the underlying mechanism of action, and clarify their side effects or toxicity with the help of modern phytochemical, pharmacological, metabonomics, and/or clinical trial methods.

Toxicity and toxicokinetics of Amanita exitialis in beagle dogs.

In this study, the toxicology of A. exitialis, a lethal mushroom found in China, and the toxicokinetics of peptide toxins contained in it were evaluated. Beagles were fed A. exitialis powder (20 or 60 mg/kg) in starch capsules, after which they were assessed for signs of toxicity, as well as biochemical and pathological changes. Ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was used to assay the peptide toxins. The total peptide toxins in A. exitialis was 3482.6 ±â€¯124.94 mg/kg. The beagles showed signs of toxicity, such as vomiting and diarrhea, at 12-48 h following ingestion of A. exitialis. Furthermore, alanine transaminase and aspartate transaminase levels in plasma, as well as prothrombin time and activated partial thromboplastin time peaked at 36 h post A. exitialis ingestion. Furthermore, total bilirubin and alkaline phosphatase levels peaked at 48 h after A. exitialis ingestion. Three dogs that were administered 60 mg/kg A. exitialis died at 24-72 h after ingesting the capsules. Additionally, liver histopathological examinations showed hemorrhagic necrosis of hepatocytes. α-Amanitin, ß-amanitin, and phallacidin were rapidly absorbed and eliminated from plasma after A. exitialis was ingested. A long latency period (12-24 h post A. exitialis ingestion) was observed in the dogs before the onset of gastrointestinal symptoms. There was acute liver damage thereafter. Gastric lavage and enhanced plasma clearance methods such as hemodialysis, hemoperfusion, or plasma exchange may be ineffective in removing amatoxins from blood at 12 h post A. exitialis ingestion. Enhanced excretion of amatoxins in urine could be effective within 2 days after ingestion of A. exitialis because amatoxins in 0-2 d urine accounted for more than 90% of the total urine excretion.

Disruption and molecular characterization of calpains-related (MoCAPN1, MoCAPN3 and MoCAPN4) genes in Magnaporthe oryzae.

Calpains are intracellular, cysteine proteases found in plants, animals and fungi functioning as signal transduction components in different cellular pathways including sporulation and alkaline adaptation in fungi. Calpains-related MoCAPN1 (MGG_14872), MoCAPN3 (MGG_15810) and MoCAPN4 (MGG_04818) genes from Magnaporthe oryzae genome which are 2604, 3513 and 771-bp in length and encoding identical proteins of 867, 1170 and 256 amino acids were functionally characterized for different phenotypes through gene disruption method. All the mutants except those for MoCAPN1 showed normal phenotypes. In pathogenicity test, the mutants did not lead to any visible changes in phenotypes causing similar blast lesions on blast susceptible rice and barley leaves as those of the Guy-11 strain suggesting no major role in pathogenicity. Germ tubes formation, appressorium formation, mycelium radial growth and mating with 2539 strain were indistinguishable among the mutants and Guy-11 strains. Cell wall integrity (congo red) test, stress response under chemical pressure (ZnSO4, CuSO4 and CdCl2), osmotic and oxidative (NaCl and H2O2) stress response, growth response on glucose and nitrogen deficient media resulted in similar results in the mutants and Guy-11 strains. However, mutants for ΔMoCAPN1 gene produced reduced (0.57±0.15B and 0.54±0.05B) conidia compared to that (1.69±0.13A) of the Guy-11 strain showing its involvement in conidiation.