Species Sensitivity Distributions of Benthic Macroinvertebrates in Fludioxonil-Spiked Sediment Toxicity Tests.

The fungicide fludioxonil, given its physicochemical properties, potentially accumulates and persists in sediments. Fludioxonil has a widespread agricultural use to control various fungal diseases. Its residues may cause toxic effects to benthic aquatic fauna, thereby impacting ecosystem service functions of aquatic ecosystems. To assess the potential environmental effects of fludioxonil in the sediment compartment of edge-of-field surface waters, sediment-spiked single-species toxicity tests with benthic macroinvertebrates were performed. In all experiments artificial sediment was used with an organic carbon content of 2.43% on dry weight basis. The single-species tests were conducted with 8 benthic macroinvertebrates covering different taxonomic groups typical for the Yangtze River Delta, China. The 28d-EC10 and 28-LC10 values thus obtained were used to construct species sensitivity distributions (SSDs). In addition, our dataset was supplemented with 28d-EC10 and 28-LC10 values for 8 different benthic invertebrates from a study in the Netherlands that used field-collected sediment. Based on SSDs constructed with 28d-EC10 or 28d-LC10 values hazardous concentrations to 5% of the species tested (HC5's) were obtained. The HC5 values based on the toxicity tests from China were lower than those from the Netherlands, although 95% confidence bands overlapped. The HC5 values derived from the separate datasets from China and the Netherlands, as well as from the combined dataset, were compared to the Tier-3 Regulatory Acceptable Concentrations (RAC) for fludioxonil and the benthic invertebrate community derived from a sediment-spiked outdoor microcosm experiment conducted in the Netherlands. The HC5 values obtained appeared to be lower than this Tier-3 RAC when expressed in terms of total sediment concentration, but not always when expressed in terms of pore water concentrations.

Establishing Standardized Biomedical Laboratory Technician Education for the Development of Biotechnology Research in China.

Chinese scientists have been actively engaged in biotechnology research since the mid-20th century. However, biotechnology education, especially biomedical laboratory technology education, is relatively scarce in China. More and more cutting-edge equipment and techniques have been introduced into biomedical laboratories in China, but there is a lack of high-quality technicians to apply these advancements to scientific research. In addition, the traditional education and apprenticeship systems have been demonstrated little progress. To address this gap, West China Hospital of Sichuan University established a 2-year educational program for laboratory technology in 2006 based on the residency training program. The project integrates scientific methods into the research laboratory technician training in relevant disciplines, and has developed a systematic, scientific, and effective standardized training system to cultivate high-level and stable experimental technician team for the need of advanced laboratories, which has been demonstrated greatly improve the efficiency of biomedical researchers and laboratory facilities. In this article, we introduce the practical experience in establishment and development of a standardized training system for biomedical laboratory technicians to ensure the sustainable development of medical researches.

Fuziline alleviates isoproterenol-induced myocardial injury by inhibiting ROS-triggered endoplasmic reticulum stress via PERK/eIF2α/ATF4/Chop pathway.

Fuziline, an aminoalcohol-diterpenoid alkaloid derived from Aconiti lateralis radix preparata, has been reported to have a cardioprotective activity in vitro. However, the potential mechanism of fuziline on myocardial protection remains unknown. In this study, we aimed to explore the efficacy and mechanism of fuziline on isoproterenol (ISO)-induced myocardial injury in vitro and in vivo. As a result, fuziline effectively increased cell viability and alleviated ISO-induced apoptosis. Meanwhile, fuziline significantly decreased the production of ROS, maintained mitochondrial membrane potential (MMP) and blocked the release of cytochrome C, suggesting that fuziline could play the cardioprotective role through restoring the mitochondrial function. Fuziline also could suppress ISO-induced endoplasmic reticulum (ER) stress via the PERK/eIF2α/ATF4/Chop pathway. In addition, using ROS scavenger NAC could decrease ISO-induced apoptosis and block ISO-induced ER stress, while PERK inhibitor GSK2606414 did not reduce the production of ROS, indicating that excess production of ROS induced by ISO triggered ER stress. And fuziline protected against ISO-induced myocardial injury by inhibiting ROS-triggered ER stress. Furthermore, fuziline effectively improved cardiac function on ISO-induced myocardial injury in rats. Western blot analysis also showed that fuziline reduced ER stress-induced apoptosis in vivo. Above these results demonstrated that fuziline could reduce ISO-induced myocardial injury in vitro and in vivo by inhibiting ROS-triggered ER stress via the PERK/eIF2α/ATF4/Chop pathway.

The cardiovascular toxicity of triadimefon in early life stage of zebrafish and potential implications to human health.

The health risk of triadimefon (TF) to cardiovascular system of human is still unclear, especially to pesticide suicides population, occupational population (farmers, retailers and pharmaceutical workers), and special population (young children and infants, pregnant women, older people, and those with compromised immune systems) who are at a greater risk. Therefore, firstly we explored the toxic effects and possible mechanism of cardiovascular toxicity induced by TF using zebrafish model. Zebrafish at stage of 48 h post fertilization (hpf) exposed to TF for 24 h exhibited morphological malformations which were further confirmed by histopathologic examination, including pericardial edema, circulation abnormalities, serious venous thrombosis and increased distance between the sinus venosus (SV) and bulbus arteriosus (BA) regions of the heart. In addition to morphological changes, TF induced functional deficits in the heart of zebrafish, including bradycardia and a significant reduced cardiac output that became more serious at higher concentrations. To better understand the possible molecular mechanisms underlying cardiovascular toxicity in zebrafish, we investigated the transcriptional level of genes related to calcium signaling pathway and cardiac muscle contraction. Q-PCR (quantitative real-time polymerase chain reaction) results demonstrated that the expression level of genes related to ATPase (atp2a1l, atp1b2b, atp1a3b), calcium channel (cacna1ab, cacna1da) and cardiac troponin C (tnnc1a) were significantly decreased after TF exposure. For the first time, the present study revealed that TF exposure had observable morphological and functional negative impacts on cardiovascular system of zebrafish. Mechanistically, this toxicity might result from the pressure of down-regulation of genes associated with calcium signaling pathway and cardiac muscle contraction following TF exposure. These findings generated here can provide information for better pesticide poisoning treatments, occupational disease prevention, and providing theoretical foundation for risk management measures.

Design, Synthesis, and Fungicidal Evaluation of Novel Pyrazole-furan and Pyrazole-pyrrole Carboxamide as Succinate Dehydrogenase Inhibitors.

The identification of novel succinate dehydrogenase (SDH) inhibitors represents one of the most attractive directions in the field of fungicide research and development. During our continuous efforts to pursue inhibitors belonging to this class, some structurally novel pyrazole-furan carboxamide and pyrazole-pyrrole carboxamide derivatives have been discovered via the introduction of scaffold hopping and bioisosterism to compound 1, a remarkably potent lead obtained by pharmacophore-based virtual screening. As a result of the evaluation against three destructive fungi, including Sclerotinia sclerotiorum, Rhizoctonia solani, and Pyricularia grisea, a majority of them displayed potent fungicidal activities. In particular, compounds 12I-i, 12III-f, and 12III-o exhibited excellent fungicidal activity against S. sclerotiorum and R. solani comparable to that of commercial SDHI thifluzamide and 1.

Effects of azocyclotin on gene transcription and steroid metabolome of hypothalamic-pituitary-gonad axis, and their consequences on reproduction in zebrafish (Danio rerio).

The widely used organotins have the potential to disrupt the endocrine system, but little is known of underlying mechanisms of azocyclotin toxicity in fish. The objective of the present study was to investigate the impact of azocyclotin on reproduction in zebrafish. Adult zebrafish were exposed to 0.09 and 0.45µg/L azocyclotin for 21days, and effects on steroid hormones and mRNA expression of the genes belonging to the hypothalamic-pituitary-gonad (HPG) axis were investigated. Mass spectrometry methodology was developed to profile steroids within the metabolome of the gonads. They were disrupted as a result of azocyclotin exposure. Alterations in the expression of key genes associated with reproductive endocrine pathways in the pituitary (lhß), gonad (cyp19a1a, cyp17a1 and 17ß-hsd3), and liver (vtg1, vtg2, cyp1a1, comt, ugt1a and gstp1) were correlated with significant reductions in estrogen in both sexes and increased testosterone in females. Azocyclotin-induced down-regulation of cyp19a1a in males suggested a reduction in the rate of estrogen biosynthesis, while up-regulation of hepatic cyp1a1 and comt in both sexes suggested an increase in estrogen biotransformation and clearance. Azocyclotin also induced change in the expression of 17ß-hsd3, suggesting increased bioavailability of 11-ketotestosterone (11-KT) in the blood. Furthermore, the down-regulation of lhß expression in the brains of azocyclotin-exposed fish was associated with inhibition of oocyte maturation in females and retarded spermatogenesis in males. As a histological finding, retarded development of the ovaries was found to be an important cause for decreased fecundity, with down-regulation of vtg suspected to be a likely underlying mechanism. Additionally, relatively high concentrations of azocyclotin in the gonads may have directly caused toxicity, thereby impairing gametogenesis and reproduction. Embryonic or larval abnormalities occurred in the F1 generation along with accumulated burdens of azocyclotin in F1 eggs, following parental exposure. Overall, our results indicate that exposure to azocyclotin can impair reproduction in fish, and induce toxicity related abnormalities in non-exposed offspring.

Competitive antagonists facilitate the recovery from desensitization of α1ß2γ2 GABAA receptors expressed in Xenopus oocytes.

AIM: The continuous presence of an agonist drives its receptor into a refractory state, termed desensitization. In this study, we tested the hypothesis that a competitive antagonist, SR95531, could facilitate the recovery of α1ß2γ2 GABAA receptor from functional desensitization. METHODS: α1ß2γ2 GABAA receptors were expressed in Xenopus oocytes. GABA-evoked currents were recorded using two-electrode voltage-clamp technique. Drugs were applied through perfusion. RESULTS: Long application of GABA (100 µmol/L) evoked a large peak current followed by a small amplitude steady-state current (desensitization). Co-application of SR95531 during the desensitization caused a larger rebound of GABA current after removal of SR95531. Furthermore, application of SR95531 after removal of GABA increased the rate of receptor recovery from desensitization, and the recovery time constant was decreased from 59±3.2 s to 33±1.6 s. SR95531-facilitated receptor recovery from desensitization was dependent on the perfusion duration of SR95531. It was also dependent on the concentration of SR95531, and the curve fitting with Hill equation revealed two potency components, which were similar to the two potency components in inhibition of the steady-state current by SR95531. Bicuculline caused similar facilitation of desensitization recovery. CONCLUSION: SR95531 facilitates α1ß2γ2 GABAA receptor recovery from desensitization, possibly through two mechanisms: binding to the desensitized receptor and converting it to the non-desensitized state, and binding to the resting state receptor and preventing re-desensitization.

Synthesis, antifungal activity, and QSAR study of novel trichodermin derivatives.

In an attempt to discover more potential antifungal agents, in this study, 21 novel trichodermin derivatives containing conjugated oxime ester (5a-5u) were designed and synthesized and were screened for in vitro antifungal activity. The bioassay tests showed that some of them exhibited good inhibitory activity against the tested pathogenic fungi. Compound 5a exhibited better activity against Pyricularia oryzae and Sclerotonia sclerotiorum than trichodermin, and compound 5j showed particular activity against P.oryzae and Botrytis cinerea. The quantitative structure-activity relationship (QSAR) indicated that log P and hardness were two critical parameters for the biological activities. The result suggested that these would be potential lead compounds for the development of fungicides with further structure modification.

Ultra performance liquid chromatography-tandem mass spectrometry for the determination of amicarthiazol residues in soil and water samples.

A reliable and rapid method has been optimized to determine the residue of amicarthiazol in soil and environmental water samples. After extraction and evaporation, the extraction was carried out with solid phase extraction (SPE) cleanup using HLB cartridge (only soil samples) and for the quantitative determination by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The resulting residues of amicarthiazol were analyzed by a gradient separation performed on a UPLC system with a C18 column, methanol and water containing 0.1% (v v(-1)) formic acid as the mobile phase in the mode of electrospray positive ionization (ESI(+)) and multiple reaction monitoring (MRM). Results showed that the recoveries for spiked samples were 74.4-97.1% and 72.1-109.9% for soil and water, respectively, with the relative standard deviation (RSD) less than 10.2% when fortified at 10, 100 and 1000µgL(-1). The limits of detection (LODs) and the limits of quantification (LOQs) for matrix matched standards ranged from 0.073-0.425µgL(-1) and 0.243-1.42µgL(-1). The intra-day precision (n=5) and the inter-day precision over 10 days (n=10) for the amicarthiazol in soils and water samples spiked at 100µgL(-1) was 7.9% and 15.9%, respectively. Results indicated that the developed method could be a helpful tool for the controlling and monitoring of the risks posed by amicarthiazol to human health and environment safety.

Synthesis and biological evaluation of novel trichodermin derivatives as antifungal agents.

To discover more potential antifungal agents, 17 novel trichodermin derivatives were designed and synthesized by modification of 3 and 4a. The structures of all the synthesized compounds were confirmed by (1)H NMR, ESI-MS and HRMS. Their antifungal activities against Ustilaginoidea oryzae and Pyricularia oryzae were evaluated. Most of the target compounds showed potent inhibitory activity, in which 4g showed superior inhibitory effects than 4a and commercial fungicide prochloraz. Furthermore, 4h demonstrated comparable inhibitory activity to 4a. Moreover, 4i and 4l exhibited excellent inhibitory activity for Pyricularia oryzae. Additionally, compound 9 was found to be more active against all tested fungal strains than 3, with EC50 values of 0.47 and 3.71 mg L(-1), respectively.

Rapid determination of quinolones in cosmetic products by ultra high performance liquid chromatography with tandem mass spectrometry.

This study developed an improved analytical method for the simultaneous quantification of 13 quinolones in cosmetics by ultra high performance liquid chromatography combined with ESI triple quadrupole MS/MS under the multiple reaction monitoring mode. The analytes were extracted and purified by using an SPE cartridge. The limits of quantification ranged from 0.03 to 3.02 µg/kg. The precision for determining the quinolones was <19.39%. The proposed method was successfully developed for the determination of quinolones in real cosmetic samples.

Disruption of zebrafish (Danio rerio) sexual development after full life-cycle exposure to environmental levels of triadimefon.

In this study, zebrafish was exposed to environmental levels of triadimefon (0.125, 0.25, 0.5 µg/mL) from 24 h post fertilization to 120 days post fertilization. Several endpoints that related to reproductive function were evaluated. It was found that the body length, body weight and vitellogenin transcription were significantly reduced for fish exposed to triadimefon. Histological examination showed that the sex ratio of fish skewed to male and female exposed to 0.5 µg/mL triadimefon had immature ovary. The breeding success, as determined from data on egg production and spawning, was reduced in fish exposed to 0.25 µg/mL triadimefon. In the offspring, the reduced egg fertility, hatching rate and survival were observed in eggs exposed to 0.5 µg/mL triadimefon. These findings indicated that triadimefon had the potential to adversely affect the sexual development and breeding success through the multiple endocrine actions.

Structure, bioactivity and implications for environmental remediation of complexes comprising the fungicide hexaconazole bound to copper.

BACKGROUND: In agricultural areas excessive amounts of toxic heavy metals are a growing threat to the environment and human health. Measures should be taken to minimise the risk of adverse health effects. Hence, we investigated the possibilities of hexaconazole (a commercial fungicidal) as a dual-function ligand that has heavy metal ions chelating and fungicidal activities. RESULTS: Metal chelation and fungicidal activities were studied by UV, elemental analysis, IR, thermogravimetric study and biological assays. Results showed that hexaconazole had selective binding capability with Cu(2+) over other ions such as Zn(2+), Cd(2+), Mn(2+), Fe(2+) and Co(2+). Soil leaching experiments showed that soil type had a limited effect on heavy-metal adsorption by hexaconazole; with decreasing pH, a notable rise of leaching effect was observed, which reached 22%. In addition, this complex exhibit better fungicidal activity against Blumeria graminis than the same dose of hexaconazole. CONCLUSION: This study demonstrates that hexaconazole had notable capabilities to chelate heavy metals as well as excellent fungicidal activity as a metal chelator. Given the mutual influence between pesticides and heavy metals in adsorption-desorption processes, these phenomena must be taken into account if they are to be applied rationally.

Metabolism-based synthesis, biological evaluation and structure-activity relationship analysis of spirotetramat analogues as potential lipid biosynthesis inhibitors.

BACKGROUND: In previous studies, scientists found that, when spirotetramat was introduced into plants or animals, it was mainly metabolised at positions C-4 and C-8. That is to say, these two functional positions potentially played an important role in spirotetramat's bioactivities. In order to develop novel insecticides or miticides, the present authors designed and synthesised 35 spirotetramat analogues based on metabolite structures. RESULTS: All of the analogues have been identified on the basis of (1)H NMR, ESI-MS and elemental analysis data. The activities of these analogues were evaluated against three organisms, and biological assays indicated that compounds 5f, 5h and 5u possessed better insecticidal activities against bean aphids (Aphis fabae) than the lead compound spirotetramat. The LC50 of 5f, 5h and 5u against bean aphids reached 0.42, 0.28 and 2.53 mg L(-1) respectively. Moreover, some compounds possessed comparable activities against carmine spider mite (Tetranychus cinnabarinus) and oriental armyworm (Mythimna sepatara) with spirotetramat. The structure-activity relationships (SARs) indicated that the flexible bridge at position C-4 of spirotetramat was important for its bioactivities, and the size of the group at position C-8 would have great influence on the activities. Furthermore, the log P values lower than 6.0 may be favourable for insecticidal activities. CONCLUSION: The present work demonstrates that some spirotetramat analogues can be used as potential lead compounds for developing novel insecticides, and preliminary SAR analysis would provide information for the utilisation of spirotetramat analogues as potential lipid biosynthesis inhibitors.

Synthesis and bioactivity evaluation of novel spiromesifen derivatives.

BACKGROUND: The development of environmentally friendly and novel structural pesticides is now an area of intense research in the agriculture field. Spirocyclic tetronic acids such as spiromesifen are typical compounds of this kind. In order to discover novel compounds with improved and broader-spectrum insecticidal activities, a series of spiromesifen derivatives were synthesised and bioassayed. RESULTS: The derivatives were identified by (1) H NMR and MS. Preliminary bioassays demonstrated that some bioactivities of compounds 5a to 5u were better and had a broader spectrum than the lead compound spiromesifen. Moreover, these compounds showed better insecticidal activities against Mythimna sepatara and Aphis fabae than acaricidal activities against Tetranychus cinnabari. Furthermore, LC(50) of 5s against Aphis fabae reached 1.09 mg L(-1) . At the same time, compounds 5g, 5i, 5k and 5r also warrant further study because of their superior bioactivities to spiromesifen. What is more, suitable carbon chain length in the 4-position ester and the log P value of these spiromesifen derivatives dramatically influenced their insecticidal activities. Butyric or pentanoic ester and a log P value of 4.0-6.0 may be preferred. CONCLUSION: The present work demonstrates that some spiromesifen derivatives can be used as potential lead compounds for developing novel insecticides and acaricides.

Design, synthesis, and biological activities of milbemycin analogues.

Milbemycins have received considerable interest in agricultural chemistry due to a special action mode, extremely high activity against arachnoide pests, low toxicity to mammals, and environmentally benign characteristics. Two series of novel milbemycin analogues (4Ia-6IIc) containing alkyl and aryl groups at the 4'- and 13-positions were designed and synthesized by five schemes. These analogues were identified by (1)H NMR, (13)C NMR, and elemental analysis (or HRMS). Their insecticidal activities against carmine spider mite, oriental armyworm, and black bean aphid were evaluated. The results showed that all of the title compounds had low acaricidal activity against carmine spider mite. However, most of them exhibited good insecticidal activities against oriental armyworm and black bean aphid at a concentration of 200 mg L(-1). The most potent substituents of 2,2-dimethylbutanoyl (4Ib), phenylacetyl (4IIm), and (Z)-1-(methoxyimino)-1-phenylacetyl (4IIn) exhibited the highest larvicidal activities, and its insecticidal LC(50) values against oriental armyworm were 0.250, 0.204, and 0.350 mg L(-1), while its insecticidal LC(50) values against black bean aphid were 0.150, 0.070, and 0.120 mg L(-1), respectively. These substituents provided some hints for further investigation on structure modification.

Pubertal exposure to thiodiazole copper inhibits thyroid function in juvenile female rats.

Thiodiazole copper, as a thiadiazole fungicide, is widely used in China. The structure of thiodiazole copper shows a close relationship with N,N-methylene-bis (2-amino-1,3,4-thiadiazole) (Bis-A-TDA), which is a teratogen. A few studies have shown that some of the thiadiazole fungicides act as endocrine disruptors via disturbance in thyroid hormone homeostasis. Little is known about the effect of pubertal exposure to thiodiazole copper on the thyroid in pubertal female rats. Based on the protocol of the 20-day Pubertal Female Assay, we attempt to estimate the possible effects of exposure to thiodiazole copper on thyroid hormone and hepatic enzyme activity in female rats. Postnatal days (PND) 22-old Sprague-Dawley rats were administered with thiodiazole copper daily by oral gavage at doses 0, 4, 10, 20 or 30mg/kg/day for 20 days. After treatments, the rats were sacrificed for blood collection; the reproductive organs, liver, pituitary, adrenal and thyroid gland were harvested. The results indicated that changes in thyroid endpoints following thiodiazole copper administration decreased serum triiodothyronine (T(3)) and thyroxine (T(4)) concentrations, increased thyroid stimulating hormone (TSH) concentrations and the weight of thyroid gland, induced hepatic uridine diphosphate glucuronyl transferase (UDPGT) activities in the highest dose group and produced thyroid gland hyperplasia. No histological changes were observed in uterus and ovaries moreover, age and weight at vaginal opening (VO) were unaffected by thiodiazole copper in all treatment groups. The absolute weights of liver and kidney were found to have decreased significantly in female rats. These data and changes demonstrate that thiodiazole copper is likely a thyroid disrupter in female rat following exposure during development, but doesnot have effect on the development of pubertal female rats. Further studies using environmentally relevant doses are needed for hazard identification.

Development of a direct competitive enzyme-linked immunosorbent assay for parathion residue in food samples.

A heterologous direct competitive enzyme-linked immunosorbent assay (ELISA) for parathion residue determination is described based on a monoclonal antibody and a new competitor. The effects of several physicochemical factors, such as methanol concentration, ionic strength, pH value, and sample matrix, on the performance of the ELISA were optimized for the sake of obtaining a satisfactory assay sensitivity. Results showed that when the assay medium was in the optimized condition (phosphate buffer solution [PBS] containing 10% [v/v] methanol and 0.2 mol/L NaCl at a pH value of 5.0), the sensitivity (estimated as the IC(50) value) and the limit of detection (LOD, estimated as the IC(10) value) were 1.19 and 0.08 ng/ml, respectively. The precision investigation indicated that the intraassay precision values all were below 10% and that the interassay precision values ranged from 4.89 to 19.12%. In addition, the developed ELISA showed a good linear correlation (r(2)=0.9962) to gas chromatography within the analyte's concentration range of 0.1 to 16 ng/ml. When applied to the fortified samples (parathion adding level: 5-15 microg/kg), the developed ELISA presented mean recoveries of 127.46, 122.52, 91.92, 124.01, 129.72, 99.37, and 87.17% for tomato, cucumber, banana, apple, orange, pear, and sugarcane, respectively. Results indicated that the established ELISA is a potential tool for parathion residue determination.

Gold immunochromatographic assay for simultaneous detection of carbofuran and triazophos in water samples.

Using a simple test for rapid identification and quantification of pesticide multiresidues in food and environmental samples is a long-cherished approach for practical monitoring purposes. Here two gold-based lateral-flow strips (strip A and strip B) were investigated for simultaneous detection of carbofuran and triazophos. For the strip A format, a bispecific monoclonal antibody (BsMcAb) against both carbofuran and triazophos was employed to prepare the immunogold probe. For the strip B format, anti-carbofuran monoclonal antibody (McAb) and anti-triazophos McAb separately labeled with colloidal gold were combined as detector reagents. By comparison of visual results from pesticide standard tests between the two formats, the strip B assay manifested higher sensitivities for both pesticides. Analysis of spiked water samples by the preferable strip indicated that the detection limits for carbofuran and triazophos were 32 and 4 microg/L, respectively. The strength of the portable one-step strip assay was in the simultaneous screening for two pesticides within a short time (8-10 min) without any equipment.

Trichodermol (4α-hydr-oxy-12,13-epoxy-trichothec-9-ene).

In the title compound, C(15)H(22)O(3), the five-membered ring displays an envelope conformation, whereas the two six-membered rings show different conformations, viz. chair and half-chair. In the crystal, mol-ecules are linked through inter-molecular O-H⋯O hydrogen bonds, forming chains running along the b axis.