Fusion of two homoleptic truncated tetrahedra into a heteroleptic truncated octahedron.

The exploration of novel structures and structural transformation of supramolecular assemblies is of vital importance for their functions and applications. Herein, based on coordination-driven self-assembly, we prepare a neutral truncated tetrahedron and a heteroleptic truncated octahedron, whose structures are unambiguously confirmed by X-ray diffraction analysis. More importantly, the truncated tetrahedron is quantitatively transformed into the truncated octahedron through its fusion with another cationic truncated tetrahedron, as evidenced by fluorescence, mass and NMR spectroscopy. This study not only deepens our understanding of the process of supramolecular fusion but also opens up possibilities for the subsequent preparation of advanced supramolecular assemblies with complex structures and integrated functions.

The impact of integrated hepatitis B virus DNA on oncogenesis and antiviral therapy.

The global burden of hepatitis B virus (HBV) infection remains high, with chronic hepatitis B (CHB) patients facing a significantly increased risk of developing cirrhosis and hepatocellular carcinoma (HCC). The ultimate objective of antiviral therapy is to achieve a sterilizing cure for HBV. This necessitates the elimination of intrahepatic covalently closed circular DNA (cccDNA) and the complete eradication of integrated HBV DNA. This review aims to summarize the oncogenetic role of HBV integration and the significance of clearing HBV integration in sterilizing cure. It specifically focuses on the molecular mechanisms through which HBV integration leads to HCC, including modulation of the expression of proto-oncogenes and tumor suppressor genes, induction of chromosomal instability, and expression of truncated mutant HBV proteins. The review also highlights the impact of antiviral therapy in reducing HBV integration and preventing HBV-related HCC. Additionally, the review offers insights into future objectives for the treatment of CHB. Current strategies for HBV DNA integration inhibition and elimination include mainly antiviral therapies, RNA interference and gene editing technologies. Overall, HBV integration deserves further investigation and can potentially serve as a biomarker for CHB and HBV-related HCC.

Lost needles, pads and where to find them.

This study aims to assess the frequency and associated factors of surgical "near-miss" incidents (NMIs) in neurosurgery using an event reporting system, to inform the development of appropriate interventions. This retrospective study collected reports of NMIs in our hospital's neurosurgery operating room (OR) from January 2019 to January 2022 through an adverse event reporting system and anonymous surveys. We conducted intergroup difference analysis using t-tests and investigated factors contributing to NMIs using Pearson correlation coefficients. We further constructed multinomial logistic regression models to explore the important factors affecting the types of lost objects and search times. A total of 195 NMIs were included in this study, with the primary items lost being 62 brain cotton pads and 133 needles. Statistical analysis revealed that smaller pads (48.4%) and size 3.0 needles (49.6%) were the most commonly missed items, with the longest retrieval times. The likelihood of NMIs occurring was higher for nurses with junior and/or non-neurosurgical backgrounds (needles: 82.7%, pads: 83.9%). Furthermore, factors such as extended working hours, nighttime surgeries, larger incisions, and more surgical instruments all increased the incidence of NMIs. The results of the multinomial logistic regression model showed that the type and search time for lost needles in the OR were jointly influenced by multiple factors (p < 0.05) compared to cotton pads. The occurrence of NMIs is associated with various factors. Reporting NMIs and their causes helps identify solutions before adverse events occur, thereby enhancing patient safety.

Predicting Continuous Locomotion Modes via Multidimensional Feature Learning from sEMG.

Walking-assistive devices require adaptive control methods to ensure smooth transitions between various modes of locomotion. For this purpose, detecting human locomotion modes (e.g., level walking or stair ascent) in advance is crucial for improving the intelligence and transparency of such robotic systems. This study proposes Deep-STF, a unified end-to-end deep learning model designed for integrated feature extraction in spatial, temporal, and frequency dimensions from surface electromyography (sEMG) signals. Our model enables accurate and robust continuous prediction of nine locomotion modes and 15 transitions at varying prediction time intervals, ranging from 100 to 500 ms. Experimental results showcased Deep-STP's cutting-edge prediction performance across diverse locomotion modes and transitions, relying solely on sEMG data. When forecasting 100 ms ahead, Deep-STF achieved an improved average prediction accuracy of 96.60%, outperforming seven benchmark models. Even with an extended 500ms prediction horizon, the accuracy only marginally decreased to 93.22%. The averaged stable prediction times for detecting next upcoming transitions spanned from 31.47 to 371.58 ms across the 100-500 ms time advances. Although the prediction accuracy of the trained Deep-STF initially dropped to 71.12% when tested on four new terrains, it achieved a satisfactory accuracy of 92.51% after fine-tuning with just 5 trials and further improved to 96.27% with 15 calibration trials. These results demonstrate the remarkable prediction ability and adaptability of Deep-STF, showing great potential for integration with walking-assistive devices and leading to smoother, more intuitive user interactions.

Helicobacter pylori Outer Membrane Vesicles: Biogenesis, Composition, and Biological Functions.

Helicobacter pylori has been recognized not only as a causative agent of a spectrum of gastroduodenal diseases including chronic gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer, but also as the culprit in several extra-gastric diseases. However, the association of H. pylori infection with extra-gastric diseases remains elusive, prompting a reevaluation of the role of H. pylori-derived outer membrane vesicles (OMVs). Like other gram-negative bacteria, H. pylori constitutively sheds biologically active OMVs for long-distance delivery of bacterial virulence factors in a concentrated and protected form, averting the need of direct bacterial contact with distant host cells to induce extra-gastric diseases associated with this gastric pathogen. Additionally, H. pylori-derived OMVs contribute to bacterial survival and chronic gastric pathogenesis. Moreover, the immunogenic activity, non-replicable nature, and anti-bacterial adhesion effect of H. pylori OMVs make them a desirable vaccine candidate against infection. The immunogenic potency and safety concerns of the OMV contents are challenges in the development of H. pylori OMV-based vaccines. In this review, we discuss recent advances regarding H. pylori OMVs, focusing on new insights into their biogenesis mechanisms and biological functions.

Artificial Intelligence-Generated Patient Education Materials for Helicobacter pylori Infection: A Comparative Analysis.

BACKGROUND: Patient education contributes to improve public awareness of Helicobacter pylori. Large language models (LLMs) offer opportunities to revolutionize patient education transformatively. This study aimed to assess the quality of patient educational materials (PEMs) generated by LLMs and compared with physician sourced. MATERIALS AND METHODS: Unified instruction about composing a PEM about H. pylori at a sixth-grade reading level in both English and Chinese were given to physician and five LLMs (Bing Copilot, Claude 3 Opus, Gemini Pro, ChatGPT-4, and ERNIE Bot 4.0). The assessments of the completeness and comprehensibility of the Chinese PEMs were conducted by five gastroenterologists and 50 patients according to three-point Likert scale. Gastroenterologists were asked to evaluate both English and Chinese PEMs and determine the accuracy and safety. The accuracy was assessed by six-point Likert scale. The minimum acceptable scores were 4, 2, and 2 for accuracy, completeness, and comprehensibility, respectively. The Flesch-Kincaid and Simple Measure of Gobbledygook scoring systems were employed as readability assessment tools. RESULTS: Accuracy and comprehensibility were acceptable for English PEMs of all sources, while completence was not satisfactory. Physician-sourced PEM had the highest accuracy mean score of 5.60 and LLM-generated English PEMs ranged from 4.00 to 5.40. The completeness score was comparable between physician-sourced PEM and LLM-generated PEMs in English. Chinese PEMs from LLMs proned to have lower score in accuracy and completeness assessment than English PEMs. The mean score for completeness of five LLM-generated Chinese PEMs was 1.82-2.70 in patients' perspective, which was higher than gastroenterologists' assessment. Comprehensibility was satisfactory for all PEMs. No PEM met the recommended sixth-grade reading level. CONCLUSION: LLMs have potential in assisting patient education. The accuracy and comprehensibility of LLM-generated PEMs were acceptable, but further optimization on improving completeness and accounting for a variety of linguistic contexts are essential for enhancing the feasibility.

The influence of Type I and III collagen on the proliferation, migration and differentiation of myoblasts.

Myoblast is a kind of activated muscle stem cell. Its biological activities, such as proliferation, migration, differentiation, and fusion, play a crucial role in maintaining the integrity of the skeletal muscle system. These activities of myoblasts can be significantly influenced by the extracellular matrix. Collagen, being a principal constituent of the extracellular matrix, substantially influences these biological activities. In skeletal muscle, collagen I and III are two kinds of primary collagen types. Their influence on myoblasts and the difference between them remain ambiguous. The purpose of this study is to discover the influence of collagen I and III on biological function of myoblasts and compare their differences. We used C2C12 cell line and primary myoblasts to discover the effect of collagen I and III on proliferation, migration and differentiation of myoblasts and then performed the transcriptome sequencing and analysis. The results showed that both collagen I and III enhanced the proliferation of myoblasts, with no statistical difference between them. Similarly, collagen I and III enhanced the migration of myoblasts, with collagen I was more pronounced in Transwell assay. On the contrary, collagen I and III inhibited myoblasts differentiation, with collagen III was more pronounced at gene expression level. The transcriptome sequencing identified DEGs and enrichment analysis elucidated different terms between Type I and III collagen. Collectively, our research preliminarily elucidated the influence of collagen I and III on myoblasts and their difference and provided the preliminary experimental foundation for subsequent research.

Association between the recommended volume of leisure-time physical activity and erectile dysfunction: A cross-sectional analysis of the national health and nutrition examination survey, 2001-2004.

Objective: Physical activity-related interventions alleviate the severity of erectile dysfunction (ED), but it is unknown whether the recommended volume of physical activity (PA) or a higher level of physical activity reduces the likelihood of ED in adult males. We aimed to evaluate the association between the recommended volume of PA and ED among US male adults. Design: A nationally representative cross-sectional survey. Setting: National Health and Nutrition Examination Survey 2001-2004. Participants: A total of 2509 men aged ≥20 years were enrolled. Primary and secondary outcome measures: ED and PA were assessed by a standardised self-report questionnaire. Weighted logistic regression analysis and spline fitting were used to assess the relationship between PA volume and the odds of ED. Results: Among 2509 US adult males, the mean (standard error) age was 43.7 (0.46) years. A total of 61.1 % of men reached the recommended volume of aerobic PA. Compared with participants not meeting the PA guidelines, individuals who had recommended aerobic activities demonstrated a 34 % reduction in the odds of having ED (OR 0.66, 95 % CI 0.48-0.90; p = 0.011). Notably, according to the restricted cubic spline, we revealed a dose‒response pattern between PA volume and reduced odds of ED, even when exceeding the recommended PA levels. When compared to males with moderate-equivalent PA of less than 150 min/week, the odds of ED in those with moderate-equivalent PA levels of 150-300 min/week and >300 min/week decreased by 22 % and 39 %, respectively. Compared with participants who did not meet the PA guidelines, the multivariable-adjusted ORs (95 % CIs) of ED associated with adequate PA volumes were 0.37 (0.22-0.61) among non-smokers and 0.85 (0.57-1.25) among current smokers (p for interaction = 0.023). Conclusions and Relevance: Our findings supported the benefit of meeting the guideline-recommended PA equivalents or higher volumes for ED prevention. However, PA-related benefit might be significantly diminished by smoking.

Phosphoribosylpyrophosphate synthetase as a metabolic valve advances Methylobacterium/Methylorubrum phyllosphere colonization and plant growth.

The proficiency of phyllosphere microbiomes in efficiently utilizing plant-provided nutrients is pivotal for their successful colonization of plants. The methylotrophic capabilities of Methylobacterium/Methylorubrum play a crucial role in this process. However, the precise mechanisms facilitating efficient colonization remain elusive. In the present study, we investigate the significance of methanol assimilation in shaping the success of mutualistic relationships between methylotrophs and plants. A set of strains originating from Methylorubrum extorquens AM1 are subjected to evolutionary pressures to thrive under low methanol conditions. A mutation in the phosphoribosylpyrophosphate synthetase gene is identified, which converts it into a metabolic valve. This valve redirects limited C1-carbon resources towards the synthesis of biomass by up-regulating a non-essential phosphoketolase pathway. These newly acquired bacterial traits demonstrate superior colonization capabilities, even at low abundance, leading to increased growth of inoculated plants. This function is prevalent in Methylobacterium/Methylorubrum strains. In summary, our findings offer insights that could guide the selection of Methylobacterium/Methylorubrum strains for advantageous agricultural applications.

The role of spinal cord neuroanatomy and the variances of epidurally evoked spinal responses.

BACKGROUND: Spinal cord stimulation (SCS) has demonstrated multiple benefits in treating chronic pain and other clinical disorders related to sensorimotor dysfunctions. However, the underlying mechanisms are still not fully understood, including how electrode placement in relation to the spinal cord neuroanatomy influences epidural spinal recordings (ESRs). To characterize this relationship, this study utilized stimulation applied at various anatomical sections of the spinal column, including at levels of the intervertebral disc and regions correlating to the dorsal root entry zone. METHOD: Two electrode arrays were surgically implanted into the dorsal epidural space of the swine. The stimulation leads were positioned such that the caudal-most electrode contact was at the level of a thoracic intervertebral segment. Intraoperative cone beam computed tomography (CBCT) images were utilized to precisely determine the location of the epidural leads relative to the spinal column. High-resolution microCT imaging and 3D-model reconstructions of the explanted spinal cord illustrated precise positioning and dimensions of the epidural leads in relation to the surrounding neuroanatomy, including the spinal rootlets of the dorsal and ventral columns of the spinal cord. In a separate swine cohort, implanted epidural leads were used for SCS and recording evoked ESRs. RESULTS: Reconstructed 3D-models of the swine spinal cord with epidural lead implants demonstrated considerable distinctions in the dimensions of a single electrode contact on a standard industry epidural stimulation lead compared to dorsal rootlets at the dorsal root entry zone (DREZ). At the intervertebral segment, it was observed that a single electrode contact may cover 20-25% of the DREZ if positioned laterally. Electrode contacts were estimated to be ~0.75 mm from the margins of the DREZ when placed at the midline. Furthermore, ventral rootlets were observed to travel in proximity and parallel to dorsal rootlets at this level prior to separation into their respective sides of the spinal cord. Cathodic stimulation at the level of the intervertebral disc, compared to an 'off-disc' stimulation (7 mm rostral), demonstrated considerable variations in the features of recorded ESRs, such as amplitude and shape, and evoked unintended motor activation at lower stimulation thresholds. This substantial change may be due to the influence of nearby ventral roots. To further illustrate the influence of rootlet activation vs. dorsal column activation, the stimulation lead was displaced laterally at ~2.88 mm from the midline, resulting in variances in both evoked compound action potential (ECAP) components and electromyography (EMG) components in ESRs at lower stimulation thresholds. CONCLUSION: The results of this study suggest that the ECAP and EMG components of recorded ESRs can vary depending on small differences in the location of the stimulating electrodes within the spinal anatomy, such as at the level of the intervertebral segment. Furthermore, the effects of sub-centimeter lateral displacement of the stimulation lead from the midline, leading to significant changes in electrophysiological metrics. The results of this pilot study reveal the importance of the small displacement of the electrodes that can cause significant changes to evoked responses SCS. These results may provide further valuable insights into the underlying mechanisms and assist in optimizing future SCS-related applications.

Predictive value of interleukin-6 combined with serum neuron-specific enolase on the prognosis of acute ischemic stroke.

OBJECTIVE: To explore the prognostic value of interleukin-6 (IL-6) combined with serum neuron specific enolase (NSE) in arterial atherosclerotic ischemic stroke. METHODS: 116 patients with arterial atherosclerotic ischemic stroke admitted to the emergency ward of our Hospital were retrospectively analyzed. According to the score of modified Rankin scale (mRS) at 90 days after discharge, the patients were divided into the poor prognosis group (mRS > 2, n = 32) and the good prognosis group (mRS ≤ 2, n = 84). Activities of Daily Living (ADL) was used to evaluate the level of independence in activities of daily living after treatment. RESULTS: The NIHSS score (14.91 ± 5.20 vs. 9.43 ± 4.30, P < 0.001), IL-6 (11.30 ± 3.11 vs. 6.75±1.28, P < 0.001) and NSE levels (12.47 ± 4.69 vs. 6.42 ± 1.32, P<0.001) in poor prognosis group were higher than those in the good prognosis group. At 90 days post-discharge, 100 % of the good prognosis group had ADL scores over 60, while in the poor prognosis group, 46.88 % scored 40-60, 40.63 % scored 20-40, 9.38 % scored under 20, and 3.13 % died. The AUC of NSE was 0.906 (95 % CI: 0.847-0.965, P < 0.001), the best cut-off value was 7.445 ng/mL, and the sensitivity and specificity were 75.0 % and 82.1 %, respectively. The AUC for IL-6 combined with NSE increased to 0.965 (95 %CI: 0.934-0.997, P < 0.001), and the sensitivity and specificity increased to 80.2 % and 92.9 %, respectively. CONCLUSION: IL-6 ≥ 6.805 pg/mL and NSE ≥ 7.445 ng/mL were independently associated with poor prognosis in patients with AIS, and the combined testing of the two indicators had a higher predictive value. These results suggested that the combined assay of IL-6 and NSE could be a novel marker for predicting poor prognosis in AIS.

Liver autotransplantation and atrial reconstruction on a patient with multiorgan alveolar echinococcosis: a case report.

BACKGROUND: Alveolar echinococcosis (AE) primarily affects the liver and potentially spreads to other organs. Managing recurrent AE poses significant challenges, especially when it involves critical structures and multiple major organs. CASE PRESENTATION: We present a case of a 59-year-old female with recurrent AE affecting the liver, heart, and lungs following two previous hepatectomies, the hepatic lesions persisted, adhering to major veins, and imaging revealed additional diaphragmatic, cardiac, and pulmonary involvement. The ex vivo liver resection and autotransplantation (ELRA), first in human combined with right atrium (RA) reconstruction were performed utilizing cardiopulmonary bypass, and repairs of the pericardium and diaphragm. This approach aimed to offer a potentially curative solution for lesions previously considered inoperable without requiring a donor organ or immunosuppressants. The patient encountered multiple serious complications, including atrial fibrillation, deteriorated liver function, severe pulmonary infection, respiratory failure, and acute kidney injury (AKI). These complications necessitated intensive intraoperative and postoperative care, emphasizing the need for a comprehensive management strategy in such complicated high-risk surgeries. CONCLUSIONS: The multidisciplinary collaboration in this case proved effective and yielded significant therapeutic outcomes for a rare case of advanced hepatic, cardiac, and pulmonary AE. The combined approach of ELRA and RA reconstruction under extracorporeal circulation demonstrated distinct advantages of ELRA in treating complex HAE. Meanwhile, assessing diaphragm function during the perioperative period, especially in patients at high risk of developing pulmonary complications and undergoing diaphragmectomy is vital to promote optimal postoperative recovery. For multi-resistant infection, it is imperative to take all possible measures to mitigate the risk of AKI if vancomycin administration is deemed necessary.

Epirubicin induces cardiotoxicity through disrupting ATP6V0A2-dependent lysosomal acidification and triggering ferroptosis in cardiomyocytes.

Epirubicin (EPI) is effective in the treatment of malignant cancers, but its application is limited by life-threatening cardiotoxicity. Iron homeostasis disturbance has been implicated in anthracycline induced cardiotoxicity (AIC), and ferroptosis is involved in AIC which dependent upon intracellular iron. However, the role and exact mechanisms of ferroptosis in the pathogenesis of epirubicin-induced cardiotoxicity (EIC) remain elusive. In this study, we aimed to investigate mechanisms underlying ferroptosis-driven EIC. Epirubicin triggered ferroptosis both in vivo and in cultured cardiomyocytes, and pretreatment with ferroptosis inhibitor, Ferrostatin-1(Fer-1) alleviates EIC. Microarray analysis was performed to screen for potential molecules involved in EIC in neonatal primary mouse ventricular cardiomyocytes (NMVMs). We found that the transcript level of ATP6V0A2, a subunit of vacuolar ATPase (V-ATPase), was significantly downregulated when NMVMs were subjected to EPI, which was verified in vivo and in vitro as measured by real time quantitative reverse transcription PCR (qRT-PCR) and immunoblotting. Intriguingly, overexpression of ATP6V0A2 effectively decreased excessive oxidative stress and lipid-peroxidation accumulation, thereby inhibiting ferroptosis and protecting cardiomyocytes against EIC, as evidenced by functional, enzymatic, and morphological changes. Mechanistically, forced expression of ATP6V0A2 restored lysosomal acidification in EPI-treated cardiomyocytes and protected cardiomyocytes and mice hearts from ferroptosis-driven EIC. In this study, our data elucidate that ferroptosis is involved in EIC, which is ignited by ATP6V0A2-dependent lysosomal acidification dysfunction. Our study provides a new potential therapeutic target for ameliorating EIC.

Carboxylic acid isomer-directed synthesis of CdS nanocluster isomers.

Selective synthesis of nanocluster (NC) isomers with tailored structures holds significant importance for enhancing their applications. Here, we develop an effective strategy for the selective synthesis of CdS NC isomers through the judicious choice of a pair of carboxylic acid isomer additives. Specifically, CdS NC-312 and NC-323 (denoted by their UV-vis absorption peak position) could be selectively produced by introducing a conventional mixture of Cd and S precursors, with the addition of 2-methylbutyric acid (2-MA) and 3-methylbutyric acid (3-MA), respectively. The synthesized NC isomers demonstrated a precise isomeric relationship, sharing both the isomeric inorganic core and organic surface. Alternatively, the as-synthesized NCs were interconvertible by re-adding the acid isomers. The density functional theory calculations further support that 2-MA and 3-MA have specific selectivity for producing CdS NC isomers by interfacial tuning. Finally, the generality of this methodology was also evidenced with applications in other CdS NC synthetic systems. This study unveils the intriguing correlation between additive structures and the configuration of NCs, providing a foundation for the selective synthesis of NC isomers.

Review of Progress in Interventional Therapy for Coronary Bifurcation Lesions.

Despite a decade of extensive research and clinical insights, percutaneous coronary intervention strategies for coronary bifurcation lesions have remained a challenging and highly debated area. This article presents a review of the latest findings and advances in defining and classifying coronary bifurcation lesions, in vitro studies, intracoronary imaging, stenting strategies, and the deployment of drug-coated balloons. Based on current evidence, this review provides recommendations for interventional cardiologists to develop individualized interventional strategies and enhance the efficiency of stenting procedures.

Integration of Perylene Diimide into a Covalent Organic Framework for Photocatalytic Oxidation.

Perylene diimides (PDIs) have garnered considerable attention due to its immense potential in photocatalysis. However, manipulating the molecular packing within their aggregates and enhancing the efficiency of photogenerated carrier recombination remain significant challenges. In this study, we demonstrate the incorporation of a PDI unit into a covalent organic framework (COF), named PDI-PDA, by linking an ortho-substituted PDI with p-phenylenediamine (PDA) to control its intermolecular aggregation. The incorporation enables precise modulation of electron transfer dynamics, leading to a ten-fold increase in the efficiency of photocatalytic oxidation of thioether to sulfoxide with PDI-PDA compared to the PDI molecular counterpart, achieving yields exceeding 90%. Electron property studies and density functional theory calculations show that the PDI-PDA with its well-defined crystal structure, enhances π-π stacking and lowers the electron transition barrier. Moreover, the strong electron-withdrawing ability of the PDI unit promotes the spatial separation of the valency band maximum and conduction band minimum of PDI-PDA suppressing the rapid recombination of photogenerated electron-hole pairs and improving charge separation efficiency to give high photocatalytic efficiency. This study provides a brief yet effective way for the improvement of the photocatalytic efficiency of commonly used PDI-based dyes by integrating them into a framework skeleton.

Integrated transcriptome and metabolomic analyses uncover the mechanism of cadmium-caused mouse spermatogonia apoptosis via inducing endoplasmic reticulum stress.

Cadmium (Cd) is a well-recognized male reproductive toxicant that can cause testicular germ cell apoptosis. However, the underlying mechanism needs investigation. CG-1 mouse spermatogonia (spg) cells were treated with 20 µM cadmium chloride (CdCl2) for 24 h. Cell apoptosis was measured, and the expressions of key genes and protein biomarkers involved in endoplasmic reticulum (ER) stress were detected, respectively. Untargeted metabolomics was performed to identify different metabolites, and transcriptome analysis was conducted to screen differentially expressed genes (DEGs). Our results indicated that CdCl2 exposure caused cell apoptosis, and DEGs were involved in several apoptosis-related pathways. Moreover, CdCl2 exposure apparently increased the mRNA and protein expressions levels of both GRP78 and ATF6α, disrupting the expression of various metabolites, particularly amino acids. Conclusively, our study reveals the pathway of CdCl2 toxicity on mouse spg, providing a deep understanding of CdCl2-induced testicular toxicity.