Search

Background: Cuproptosis is a novel copper-dependent mode of cell death that has recently been discovered. The relationship between Cuproptosis-related ncRNAs and breast cancer subtypes, however, remains to be studied. Methods: The aim of this study was to construct a breast cancer subtype prediction model associated with Cuproptosis. This model could be used to determine the subtype of breast cancer patients. To achieve this aim, 21 Cuproptosis-related genes were obtained from published articles and correlation analysis was performed with ncRNAs differentially expressed in breast cancer. Random forest algorithms were subsequently utilized to select important ncRNAs and build breast cancer subtype prediction models. Results: A total of 94 ncRNAs significantly associated with Cuproptosis were obtained and the top five essential features were chosen to build a predictive model. These five biomarkers were differentially expressed in the five breast cancer subtypes and were closely associated with immune infiltration, RNA modification, and angiogenesis. Conclusion: The random forest model constructed based on Cuproptosis-related ncRNAs was able to accurately predict breast cancer subtypes, providing a new direction for the study of clinical therapeutic targets. [ABSTRACT FROM AUTHOR]

The surge of health misinformation on social media poses a threat to public health. This qualitative study reports how users process health misinformation from the dominant strong-tie social media, WeChat, in China. We conducted ten on-site focus groups involving 76 adult participants. Drawing on the apomediation theory and the dual processing model of credibility assessment, we found the heuristic approach to processing health information was the dominant route of engagement. We identified four categories of credibility assessment cues, including (1) expertise, authority, and commercial intent of original sources, (2) expertise of apomediaries (i.e. social media information sharers) and generational bias, (3) clickbait and sensational content versus objective scientific style, and (4) disconfirmation versus confirmation bias. We highlight that apomediaries are playing an increasingly important role in informing credibility judgment. Specifically, younger adults have formed a generational bias of deeming older apomediaries as cues of lower credibility. [ABSTRACT FROM AUTHOR]

Previous studies have found that activated CD8+ T cells secrete elevated levels of interferon‐gamma (IFN‐γ) to trigger ferroptosis in tumor cells. However, IFN‐γ‐mediated ferroptosis is induced at low levels in tumor cells because of the limited IFN‐γ secreted by CD8+ T cells in the immunosuppressive tumor microenvironment. Recent studies have shown that manganese ion can activate the cyclic guanosine monophosphate‐adenosine monophosphate (GMP–AMP) synthase/stimulator of interferon genes (cGAS‐STING) pathway and support adaptive immune responses against tumors, which enhances the level of tumor‐infiltrating CD8+ T cells. Therefore, tumor microenvironment‐responsive Mn‐based nanoenzymes (Mn‐based NEs) that activated the cGAS‐STING pathway are designed to amplify immune‐driven ferroptosis. The multifunctional all‐in‐one nanoplatform is simply and mildly synthesized by the coordination between Mn3+ ions and 3,3′‐dithiodipropionic acid. After intracellular delivery, each component of Mn‐based NEs exerts its function. That is, glutathione is depleted through disulfide–thiol exchange and redox pair of Mn3+/Mn2+, a hydroxyl radical (·OH) is generated via the Fenton‐like reaction to cause ferroptosis, and Mn2+ augments cGAS‐STING activity to boost immune‐driven ferroptosis. In addition, ferroptosis amplifies Mn2+‐induced immunogenic cell death and initiates the antitumor immune "closed loop" along with immune‐driven ferroptosis. Notably, this multifunctional nanoplatform is effective in killing both primary and distant tumors. [ABSTRACT FROM AUTHOR]

This research is devoted to modelling the viscoplastic deformation behaviour and microstructure evolution of particle reinforced titanium matrix composites (TMCs) at hot working conditions. A series of Gleeble hot compression tests were conducted to obtain the stress-strain curves. According to the dominant mechanisms of TMCs during deformation, a set of mechanism-based constitutive equations was developed and fitted based on the experiment data. Lamellar alpha globularisation, dynamic recrystallization and damage were considered and incorporated into the constitutive equations to describe the viscoplastic flow behaviour.

Different volume fraction of TiB, TiC and La2O3 multiple-reinforced Ti6Al4V composites were fabricated by casting and followed by forging and hot extrusion. The microstructural evolution and mechanical behavior of (TiB+TiC+La2O3)/Ti6Al4V composites during hot extrusion were investigated. The microstructural observations showed that the TiBw and TiCp agglomeration disappeared and distributed more homogeneously in the Ti matrix after hot extrusion. Besides, TiBw exhibited highly preferred alignment along the extrusion direction and TiCp distributed along the same direction. Besides, two kinds of microstructure bands with distinctive spatial distributions of reinforcements were formed after hot extrusion: equiaxial bands embedded with fairly substantial reinforcements and finer basket-weave bands containing few reinforcements, in which the micron-scale TiBw, TiCp and submicron-scale La2O3 particle stimulating nucleation occurred and resulting dynamic recrystallization were the main mechanisms responsible for grain refinement. The tensile tests revealed that hot extrusion significantly increased elongation of (TiB+TiC+La2O3)/Ti6Al4V composites from 2.71% to 13.2% accompanied by slightly decreasing ultimate tensile strength from 954MPa to 903MPa, compared with that of the as-forged composites, which due to a complex process of reinforcements/matrix interaction during extrusion and dynamic recrystallization.

Lactococcus lactis subsp. lactis is a food bacterium that has been utilized for decades in food fermentation and the development of high-value industrial goods. Among these, nisin, which is produced by several strains of L. lactis subsp. lactis, plays a crucial role as a food bio-preservative. The gene expression for nisin synthesis was evaluated using qPCR analysis. Additionally, a series of re-transformations of the strain introducing multiple copies of the nisA and nisRK genes related to nisin production were developed. The simultaneous expression of nisA and nisZ genes was used to potentiate the effective inhibition of foodborne pathogens. Furthermore, qPCR analysis indicated that the nisA and nisRK genes were expressed at low levels in wild-type L. lactis subsp. lactis. After several re-transformations of the strain with the nisA and nisRK genes, a high expression of these genes was obtained, contributing to improved nisin production. Also, co-expression of the nisA and nisZ genes resulted in extremely effective antibacterial action. Hence, this study would provide an approach to enhancing nisin production during industrial processes and antimicrobial activity. [ABSTRACT FROM AUTHOR]

Cascade reactions catalyzed by multi-enzyme systems are important in science and industry and can be used to synthesize drugs and nutrients. In this study, two types of macromolecules of bi-enzyme self-assembly clusters (BESCs) consisting of carbonyl reductase (CpCR) and glucose dehydrogenase (GDH) were examined. Stereoselective CpCR and GDH were successfully fused with SpyCatcher and SpyTag, respectively, to obtain four enzyme modules, namely: SpyCatcher-CpCR, SpyCatcher-GDH, SpyTag-CpCR, and SpyTag-GDH, which were covalently coupled in vitro to form two types of hydrogel-like BESCs: CpCR-SpyCatcher-SpyTag-GDH and GDH-SpyCatcher-SpyTag-CpCR. CpCR-SpyCatcher-SpyTag-GDH showed a better activity and efficiently converted ethyl 2-oxo-4-phenylbutyrate (OPBE) to ethyl(R)2-hydroxy-4-phenylbutanoate ((R)-HPBE), while regenerating NADPH. At 30 °C and pH 7, the conversion rate of OPBE with CpCR-SpyCatcher-SpyTag-GDH as a catalyst reached 99.9%, with the ee% of (R)-HPBE reaching above 99.9%. This conversion rate was 2.4 times higher than that obtained with the free bi-enzyme. The pH tolerance and temperature stability of the BESCs were also improved compared with those of the free enzymes. In conclusion, bi-enzyme assemblies were docked using SpyCatcher/SpyTag to produce BESCs with a special structure and excellent catalytic activity, improving the catalytic efficiency of the enzyme. [ABSTRACT FROM AUTHOR]

(R)-1-[3,5-bis(trifluoromethyl)phenyl]ethanamine, a key chiral intermediate of selective tetrodotoxin-sensitive blockers, was efficiently synthesized by a bienzyme cascade system formed by with R-ω-transaminase (ATA117) and an alcohol dehydrogenase (ADH) co-expression system. Herein, we report that the use of ATA117 as the biocatalyst for the amination of 3,5-bistrifluoromethylacetophenone led to the highest efficiency in product performance (enantiomeric excess > 99.9%). Moreover, to further improve the product yield, ADH was introduced into the reaction system to promote an equilibrium shift. Additionally, bienzyme cascade system was constructed by five different expression systems, including two tandem expression recombinant plasmids (pETDuet-ATA117-ADH and pACYCDuet-ATA117-ADH) and three co-expressed dual-plasmids (pETDuet-ATA117/pET28a-ADH, pACYCDuet-ATA117/pET28a-ADH, and pACYCDuet-ATA117/pETDuet-ADH), utilizing recombinant engineered bacteria. Subsequent studies revealed that as compared with ATA117 single enzyme, the substrate handling capacity of BL21(DE3)/pETDuet-ATA117-ADH (0.25 g wet weight) developed for bienzyme cascade system was increased by 1.50 folds under the condition of 40 °C, 180 rpm, 0.1 M pH9 Tris-HCl for 24 h. To the best of our knowledge, ours is the first report demonstrating the production of (R)-1-[3,5-bis(trifluoromethyl)phenyl]ethanamine using a bienzyme cascade system, thus providing valuable insights into the biosynthesis of chiral amines. [ABSTRACT FROM AUTHOR]

While a few derivatives of cinnamamides exhibited anti-inflammatory and/ or analgesic activity, in this study, we developed a highly efficient method for the synthesis of cinnamamides from methyl cinnamates and phenylethylamines catalyzed by Lipozyme® TL IM in continuous-flow microreactors. The reaction parameters and broad substrate range of the new method was studied. Maximum conversion (91.3%) was obtained under the optimal condition of substrate molar ratio of 1:2 (methyl 4-chlorocinnamate: phenylethylamine) at 45 ° C for about 40 min. The remarkable features of this work include short residence time, mild reaction conditions, easy control of the reaction process, and that the catalyst can be recycled or reused, which provide a rapid and economical strategy for the synthesis and design of cinnamamide derivatives for further research on drug activity. [ABSTRACT FROM AUTHOR]

In nature, plants interact with a wide range of microorganisms, and most of these microorganisms could induce growth through the activation of important molecular pathways. The current study evaluated whether the endophytic bacterium Bacillus aryabhattai encourages plant growth and the transcriptional changes that might be implicated in this effect. The endophytic bacterium promotes the growth of Arabidopsis and tobacco plants. The transcriptional changes in Arabidopsis plants treated with the bacterium were also identified, and the results showed that various genes, such as cinnamyl alcohol dehydrogenase, apyrase, thioredoxin H8, benzaldehyde dehydrogenase, indoleacetaldoxime dehydratase, berberine bridge enzyme-like and gibberellin-regulated protein, were highly expressed. Also, endophytic bacterial genes, such as arginine decarboxylase, D-hydantoinase, ATP synthase gamma chain and 2-hydroxyhexa-2,4-dienoate hydratase, were activated during the interaction. These findings demonstrate that the expression of novel plant growth-related genes is induced by interaction with the endophytic bacterium B. aryabhattai and that these changes may promote plant growth in sustainable agriculture. [ABSTRACT FROM AUTHOR]

Background: At present, chemotherapy is still the primary treatment for advanced biliary tract carcinoma, but it is challenging to balance the efficacy and side effects. Network meta-analysis (NMA) is a better way to identify the protocol, and the advantage is that it can be combined with direct and indirect evidence to judge the best treatment regimens. Therefore, we conducted NMA on the searched randomized controlled trials (RCTs). Methods: NMA was conducted regarding the searched RCTs by comparing progression-free survival (PFS), overall survival (OS), objective remission rates (ORRs), and adverse events (AEs) of different chemotherapy protocols. Results: We screened 24 studies that met the inclusion criteria for further analysis. Compared with other regimens, the best supportive care (BSC) or FUFA protocol has a worse OS. Folfox4, GEMOX+erlotinib, and C+GEMOX can improve patients' PFS compared with BSC. Patients receiving GP+cediranib protocol have higher ORRs. There was reduced neutropenia grade ≥3 when adopting GP+cediranib, GS, C+GEMOX, RAM+GP, and MER+GP than when using FUFA protocol. The probability of vomiting of XELOX is lower than that of GEM+XELOX. There is a lower diarrhea incidence of XELOX than that of GEMOX+erlotinib. The results of cluster grade analysis illustrated that GEMOX+erlotinib owned a higher ORR and a higher surface under the cumulative ranking (SUCRA) of neutropenia and vomiting but also had a lower SUCRA of diarrhea and fatigue. Meanwhile, both GEMOX and C+GEMOX have a better ORR and a higher AE SUCRA. Conclusion: The NMA demonstrated that chemotherapy combined with targeted therapy has better efficacy and lower incidence of AEs than chemotherapy alone. [ABSTRACT FROM AUTHOR]

The identification and use of endophytic bacteria capable of triggering plant growth is an important aim in sustainable agriculture. In nature, plants live in alliance with multiple plant growth-promoting endophytic microorganisms. In the current study, we isolated and identified a new endophytic bacterium from a wild plant species Glyceria chinensis (Keng). The bacterium was designated as a Bacillus altitudinis strain using 16S rDNA sequencing. The endophytic B. altitudinis had a notable influence on plant growth. The results of our assays revealed that the endophytic B. altitudinis raised the growth of different plant species. Remarkably, we found transcriptional changes in plants treated with the bacterium. Genes such as maturase K, tetratricopeptide repeat-like superfamily protein, LOB domain-containing protein, and BTB/POZ/TAZ domain-containing protein were highly expressed. In addition, we identified for the first time an induction in the endophytic bacterium of the major facilitator superfamily transporter and DNA gyrase subunit B genes during interaction with the plant. These new findings show that endophytic B. altitudinis could be used as a favourable candidate source to enhance plant growth in sustainable agriculture. [ABSTRACT FROM AUTHOR]

Constitutive activation of Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most common oncogenic event in certain types of human cancer and is associated with poor patient survival. Small molecule signaling inhibitors have improved the clinical outcomes of patients with various cancer types but attempts to target KRAS have been unsuccessful. Plinabulin represents a novel class of agents that inhibit tubulin polymerization with a favorable safety profile in clinical trials. In the present study, the potency of plinabulin to inhibit tubulin polymerization and growth of KRAS-driven cancer cells was characterized. In vivo efficacy of plinabulin was tested in two different mouse models; one being the RCAS/t-va gene transfer system and the other being a xenograft model. In vitro cell culture tubulin polymerization assays were used to complement the mouse models. There was improved survival in a KRAS-driven mouse gene transfer glioma model, but lack of benefit in a similar model, without constitutively active KRAS, which supports the notion of a KRAS-specific effect. This survival benefit was mediated, at least in part, by the ability of plinabulin to inhibit tubulin polymerization and disrupt endosomal recycling. It was proposed a mechanism of compromised endosomal recycling of displaced KRAS through targeting microtubules that yields inhibition of protein kinase B, but not extracellular signal regulated kinase (ERK) signaling, therefore lending rationale to combination treatments of tubulin- and ERK-targeting agents in KRAS-driven cancer. [ABSTRACT FROM AUTHOR]

Biometrics refers to metrics related to human characteristics and traits such as finger prints. How to use biometric to replace an encryption key or an identity certificate efficiently and securely is a hot topic in this big data era. In this field, secure biometric authentication is an important application, which refers to automated authentication based on their encrypted biological and behavioral traits. Searchable encryption is a powerful technology supporting retrieval for encrypted data with specific encrypted keyword index. It also has a profound meaning in the big data field. In this paper, we propose a generic transformation from searchable encryption to secure biometric authentication and construct a specific secure biometric authentication scheme based on public key encryption with keyword search (PEKS). The security of this authentication relies on the distinguishability of trapdoors and indexes in PEKS. In our scheme, the user does not need to claim the target user to authenticate in authentication message, and we change the pattern of authenticating by one bit. Compared with some existing authentication scheme, the proposed scheme is more efficient in the practical application. Furthermore, searchable encryption is an earlier cryptographic system that has relatively mature methods. Our transformation from searchable encryption to secure biometric authentication presents a new direction of constructing authentication scheme. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The preparation of thioesters through the lipase-catalysed transesterification reaction of thiols with vinyl carboxyl esters is described. The reactions were carried out by Lipase TL IM from Thermomyces lanuginosus as a catalyst and performed under a continuous flow microreactor. We first found that lipase TL IM can be used in the reaction of thioester synthesis with high efficiency. Various reaction parameters were investigated including substrate molar ratio, reaction time, and temperature. Maximum conversion (96%) was obtained under the optimal condition of a substrate molar ratio of 1:2 (4-methylbenzyl mercaptan:vinyl esters) at 50 °C for about 30 min. Compared with other methods, the salient features of this work include mild reaction conditions (50 °C), short reaction times (30 min), high yields, and environment-friendliness. [ABSTRACT FROM AUTHOR]

[Display omitted] As a non-invasive imaging monitoring method, molecular imaging can provide the location and expression level of disease signature biomolecules in vivo, leading to early diagnosis of relevant diseases, improved treatment strategies, and accurate assessment of treating efficacy. In recent years, a variety of nanosized imaging probes have been developed and intensively investigated in fundamental/translational research and clinical practice. Meanwhile, as an interdisciplinary discipline, this field combines many subjects of chemistry, medicine, biology, radiology, and material science, etc. The successful molecular imaging not only requires advanced imaging equipment, but also the synthesis of efficient imaging probes. However, limited summary has been reported for recent advances of nanoprobes. In this paper, we summarized the recent progress of three common and main types of nanosized molecular imaging probes, including ultrasound (US) imaging nanoprobes, magnetic resonance imaging (MRI) nanoprobes, and computed tomography (CT) imaging nanoprobes. The applications of molecular imaging nanoprobes were discussed in details. Finally, we provided an outlook on the development of next generation molecular imaging nanoprobes. [ABSTRACT FROM AUTHOR]

Abstract (TiB + La 2 O 3)/Ti composites with different initial structures were obtained through designed heat treatment. The isothermal deformation and spheroidization mechanisms of (TiB + La 2 O 3)/Ti composites with different initial structures were investigated. Initial structures were refined as the heat treatment temperature decreased. Simultaneously, the quenching and reheating resulted in finer α lamella colonies and α interlamellar spacing compared to the furnace cooling. The flow resistance of furnace cooled samples was lower than the quenched and reheated samples in terms of flow stress data. Following the deformation at 920 °C, the furnace cooled samples demonstrated lamellar α phase and partial spheroidized structure. Moreover, the spheroidization mechanism was similar to the boundary splitting model. Recrystallized grains of approximately 1 μm in diameter were obtained in the quenched and reheated sample following deformation at 920 °C. The spheroidization mechanism was attributed to the development of finer needles through quenching and reheating, as well as to subsequent dynamic recrystallization during the hot deformation. Additionally, the dislocation movement was blocked by the reinforcements on account of the composites with micron TiB and submicron La 2 O 3 during the hot deformation. Furthermore, the reinforcements could facilitate the dynamic recrystallization (DRX) of the α phase. Graphical Abstract (TiB + La 2 O 3)/Ti composites with different initial structures were obtained through designed heat treatment. The matrix was composed of lamellar α phase and acicular α phase at 920 °C, respectively. In the following deformation, the furnace cooled samples demonstrated lamellar α phase and partial spheroidized structure. Moreover, the spheroidization mechanism was similar to the boundary splitting model. The spheroidization of quenched and reheated samples occurred as complete, while high amounts of fine equiaxed grains were obtained, due to the dynamic recrystallization in the subsequent deformation. Refined lamellar microstructures could promote dynamic recrystallization. Unlabelled Image Highlights • Different initial microstructures were obtained through designed heat treatment. • Refined lamellar microstructures promoted dynamic recrystallization. • The spheroidization mechanism was attributed to dynamic recrystallization. • The micron TiB and submicron La 2 O 3 impeded dislocation movement. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect of astaxanthin in the treatment of mild-to-moderate dry eye disease (DED) in middle-aged and elderly patients. Methods: 120 eyes of 60 middle-aged and elderly patients with mild-to-moderate DED were enrolled in this prospective, one-group, quasi-experimental study. Six milligram Astaxanthin tablets (Weihong Haematococcus Pluvialis Astaxanthin, Hangzhou Xinwei Low Carbon Technology R&D Co., Ltd., China) were administered orally, twice daily for 30 ± 2 days. History of eye diseases, treatment, systemic disease, and medication before the test were recorded. In addition, the ocular surface disease index (OSDI) questionnaire, non-invasive tear break-up time (NIBUT), fluorescein break-up time (FBUT), corneal fluorescein staining (CFS) score, eyelid margin signs, meibomian gland (MG) expressibility, meibum quality, meibomian gland dropout (MGDR), Schirmer I test (SIt), tear meniscus height (TMH), bulbar conjunctiva congestion degree, blink frequency, incomplete blink rate, and thickness of tear film lipid layer were collected before treatment, 2 weeks after the initiation of treatment, and at the end of treatment. Visual acuity (VA), intraocular pressure (IOP), anterior segment, fundus, discomfort symptoms and other adverse reactions were also monitored throughout the study to assess the safety. Results: OSDI score, NIBUT, BUT, CFS score, eyelid margin signs, MG expressibility, meibum quality, and blink frequency improved significantly to varying degrees after treatment compared with those before the treatment ( P < 0.05), while TMH, SIt, conjunctival congestion, the thickness of tear film lipid layer, MGDR, incomplete blink rate, VA and IOP did not differ ( P > 0.05). Conclusions: Oral administration of astaxanthin improves the symptoms and signs of middle-aged and elderly patients with mild-to-moderate DED., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tian, Wen, Li, Zhang, Wang, Wang, Cao, Du, Wang and Jie.)

In this study, interface-assembled carbonyl reductase (IACR) was prepared and used in the synthesis of S-licarbazepine in a toluene/Tris-HCl biphasic system. The carbonyl reductase (CR) was conjugated with polystyrene to form a surfactant-like structure at the interface of the toluene/Tris-HCl biphasic system. The interface-assembled efficiency of IACR reached 83% when the CR (180 U/mg) and polystyrene concentration were 8 × 10² g/ml and 3.75 × 10³ g/ml, respectively. The conversion reached 95.6% and the enantiometric excess of S-licarbazepine was 98.6% when 3.97 × 10⁶ nmol/l oxcarbazepine was converted by IACR using 6% ethanol as a co-substrate in toluene/Tris-HCl (12.5:10) at 30°C and 43 × g for 6 h. IACR could be reused efficiently five times.

Developing multifunctional phototheranostics with nanoplatforms offers promising potential for effective eradication of malignant solid tumors. In this study, we develop a multifunctional phototheranostic by combining photothermal therapy (PTT) and photoacoustic therapy (PAT) based on a tumor-targeting nanoagent (DBCO-ZnPc-LP). The nanoagent DBCO-ZnPc-LP was facilely prepared by self-assembling of a single lipophilic near-infrared (NIR) dye zinc(II)-phthalocyanine (ZnPc) with a lipid-poly(ethylene glycol) (LP) and following modified further with dibenzyl cyclootyne (DBCO) for introducing the two-step chemical tumor-targeting strategy based on metabolic glycoengineering and click chemistry. The as-prepared DBCO-ZnPc-LP could not only convert NIR light into heat for effective thermal ablation but also induce a thermal-enhanced ultrasound shockwave boost to trigger substantially localized mechanical damage, achieving synergistic antitumor effect both in vitro and in vivo. Moreover, DBCO-ZnPc-LP can be efficiently delivered into tumor cells and solid tumors after being injected intravenously via the two-step tumor-targeting strategy. By integrating the targeting strategy, photoacoustic imaging, and the synergistic interaction between PTT and PAT, a solid tumor could be accurately positioned and thoroughly eradicated in vivo. Therefore, this multifunctional phototheranostic is believed to play an important role in future oncotherapy by the enhanced synergistic effect of PTT and PAT under the guidance of photoacoustic imaging.

To gain a broader insight into the role of Bcl-2 proteins in apoptosis induced after mitotic arrest, we investigated the subcellular location, oligomeric structure, and protein interactions of Bax, Bcl-2, and Bcl-xL in vinblastine-treated KB-3 cells. Vinblastine induced the translocation of Bax from the cytosol to the mitochondria, which was accompanied by conformational activation and oligomerization of Bax. Bcl-2 was located in the mitochondria, underwent multisite phosphorylation after vinblastine treatment, and was strictly monomeric under all conditions. In contrast, in control cells, Bcl-xL existed in both monomeric (30 kDa) and oligomeric (150 kDa) forms. Treatment with agents that induced Bcl-xL phosphorylation (microtubule inhibitors) caused loss of the 150-kDa form, but this species was unaffected by apoptotic stimuli that did not stimulate phosphorylation. Vinblastine also promoted Bax activation and Bax oligomerization in HCT116 colon cancer cells. Both wild-type and Bax-deficient HCT116 cells expressed the 150-kDa form of Bcl-xL, which was depleted similarly in both cell lines upon vinblastine treatment. Co-immunoprecipitation studies revealed that in untreated KB-3 cells inactive cytosolic Bax interacted with Bcl-xL, whereas in vinblastine-treated cells, activated mitochondrial Bax did not interact with Bcl-xL. Interaction of Bcl-2 with Bax was not observed under any condition. Overexpression of Bcl-xL inhibited vinblastine-induced Bax activation and Bax dimerization and in parallel inhibited apoptosis. The results indicate that vinblastine-induced apoptosis requires translocation, activation, and oligomerization of Bax and is associated with specific changes in the oligomeric properties of Bcl-xL, which occur independently of Bax.