An integrated vertex model of the mesoderm invagination during the embryonic development of Drosophila.

The mesoderm invagination of the Drosophila embryo is known as an archetypal morphogenic process. To explore the roles of the active cellular forces and the regulation of these forces, we developed an integrated vertex model that combines the regulation of morphogen expression with cell movements and tissue mechanics. Our results suggest that a successful furrow formation requires an apical tension gradient, decreased basal tension, and increased lateral tension, which corresponds to apical constriction, basal expansion, and apicobasal shortening respectively. Our model also considers the mechanical feedback which leads to an ectopic twist expression with external compression as observed in experiments. Our model predicts that ectopic invagination could happen if an external compressive gradient is applied.

Follow-up of SARS-CoV-2 positive subgroup from the Asymptomatic novel CORonavirus iNFection study.

A nested longitudinal study within theAsymptomatic novel CORonavirus iNFfection study followed participants with positive nasopharyngeal swab to query for development of symptoms and assess duration of positive reverse transcription-polymerase chain reaction (RT-PCR) test results. Of the 91 participants initially testing positive, 86 participated in follow-up approximately 14 days after study enrollment; of those 86 participants, 19 (22.1%) developed at least one symptom at any time after the initial positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result. The median number of days to symptom development after their initial positive test result was 6 (range 1-29 days). No participants reported a SARS-CoV-2-related hospitalization. The most frequently reported symptoms were fatigue or muscle aches (10.5%), headache (9.3%), fever (5.8%), and shortness of breath (5.8%). Of the 78 participants who submitted a nasopharyngeal swab for repeat RT-PCR testing, 17 (21.8%) remained positive at Day 14, 4 of which continued to test positive at Day 28. These findings reinforce the probable role of silent SARS-CoV-2 infections in community transmission, and that reliance on symptom development will miss a large proportion of infections. Broad testing programs not limited to individuals presenting with symptoms are critical for identifying persons with SARS-CoV-2 infection and ultimately slowing transmission.

Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis.

Enigmatic lipid peroxidation products have been claimed as the proximate executioners of ferroptosis-a specialized death program triggered by insufficiency of glutathione peroxidase 4 (GPX4). Using quantitative redox lipidomics, reverse genetics, bioinformatics and systems biology, we discovered that ferroptosis involves a highly organized oxygenation center, wherein oxidation in endoplasmic-reticulum-associated compartments occurs on only one class of phospholipids (phosphatidylethanolamines (PEs)) and is specific toward two fatty acyls-arachidonoyl (AA) and adrenoyl (AdA). Suppression of AA or AdA esterification into PE by genetic or pharmacological inhibition of acyl-CoA synthase 4 (ACSL4) acts as a specific antiferroptotic rescue pathway. Lipoxygenase (LOX) generates doubly and triply-oxygenated (15-hydroperoxy)-diacylated PE species, which act as death signals, and tocopherols and tocotrienols (vitamin E) suppress LOX and protect against ferroptosis, suggesting a homeostatic physiological role for vitamin E. This oxidative PE death pathway may also represent a target for drug discovery.

LPS impairs oxygen utilization in epithelia by triggering degradation of the mitochondrial enzyme Alcat1.

Cardiolipin (also known as PDL6) is an indispensable lipid required for mitochondrial respiration that is generated through de novo synthesis and remodeling. Here, the cardiolipin remodeling enzyme, acyl-CoA:lysocardiolipin-acyltransferase-1 (Alcat1; SwissProt ID, Q6UWP7) is destabilized in epithelia by lipopolysaccharide (LPS) impairing mitochondrial function. Exposure to LPS selectively decreased levels of carbon 20 (C20)-containing cardiolipin molecular species, whereas the content of C18 or C16 species was not significantly altered, consistent with decreased levels of Alcat1. Alcat1 is a labile protein that is lysosomally degraded by the ubiquitin E3 ligase Skp-Cullin-F-box containing the Fbxo28 subunit (SCF-Fbxo28) that targets Alcat1 for monoubiquitylation at residue K183. Interestingly, K183 is also an acetylation-acceptor site, and acetylation conferred stability to the enzyme. Histone deacetylase 2 (HDAC2) interacted with Alcat1, and expression of a plasmid encoding HDAC2 or treatment of cells with LPS deacetylated and destabilized Alcat1, whereas treatment of cells with a pan-HDAC inhibitor increased Alcat1 levels. Alcat1 degradation was partially abrogated in LPS-treated cells that had been silenced for HDAC2 or treated with MLN4924, an inhibitor of Cullin-RING E3 ubiquitin ligases. Thus, LPS increases HDAC2-mediated Alcat1 deacetylation and facilitates SCF-Fbxo28-mediated disposal of Alcat1, thus impairing mitochondrial integrity.

Broadband tunable filter based on the loop of multimode Bragg grating.

A broadband tunable silicon filter has been demonstrated on silicon-on-insulator platform. The device is based on the loop of multimode anti-symmetric waveguide Bragg grating. A wide bandwidth tunability about 1.455 THz (0.117-1.572 THz) is achieved. The device, functions like a ring, can realize the bandwidth tunable of the drop port and the through port. And, its feature has simultaneous wavelength tuning and no free space ranges limitation. A high out-of-band contrast of 30 dB is achieved with a bandwidth of 1.572 THz (Δλ = 13 nm). The out-of-band contrast is 18 dB at the minimum bandwidth 0.117 THz (Δλ = 1.0 nm).

Continuously tunable true-time delay lines based on a one-dimensional grating waveguide for beam steering in phased array antennas.

In this paper, we propose integrated one-dimensional (1D) grating waveguide-based true-time delay (TTD) lines on a silicon-on-insulator (SOI) platform. Through optimizing the structure of the proposed waveguide, a time delay of 77.23 ps/mm can be readily achieved in a wavelength tuning range from 1540.20 nm to 1558.97 nm. Compared to conventional photonic crystal waveguide-based TTDs, the proposed waveguide occupies 70% less chip surface and has much lower propagation loss when compared with 2D photonic crystal devices. Therefore, a larger time delay can be achieved on-chip. To facilitate low loss coupling from strip waveguides to 1D grating waveguides and vice versa, a novel step taper is designed and shows a coupling efficiency of over 78%. Based on the 1D grating waveguide, a 1×4 beam steering module is designed and simulated. A wide beam steering angle from -67.84° to 67.84° for the X-band four-element phased array antenna with an array pitch size of 1.25 cm is obtained.

Broad bandwidth and large fabrication tolerance polarization beam splitter based on multimode anti-symmetric Bragg sidewall gratings.

A novel polarization beam splitter based on an anti-symmetric sidewall Bragg grating in a multimode silicon-on-insulator strip waveguide is demonstrated. Anti-symmetric spatially periodic refractive-index perturbations are designed for strong coupling between the fundamental (TE0) and the first-order transverse electric modes (TE1), while not for transfer magnetic modes. An adiabatic coupler is cascaded at the input-port, so as to drop the TE1 reflection. The Bragg grating has a compact length of ∼20 µm (55 periods). The polarization isolations of the through- and drop-ports at the wavelength of 1557 nm are 34 and 31 dB, respectively. A broad bandwidth of 64 nm and a large fabrication tolerance of 80 nm for polarization isolation over 20 dB are also achieved.

Silicon lateral-apodized add-drop filter for on-chip optical interconnection.

A lateral-apodized add-drop filter is demonstrated in a multimode asymmetric waveguide Bragg grating. This design utilizes two individual superposed gratings with the same sidewall corrugation depth. The strong side lobes of the grating filter are efficiently suppressed by mapping the target apodization profile into lateral shifts between the periods of the two gratings. Compared with other apodized technology, this device is easier to be realized. Experimental results show that the side-lobes suppression ratio can reach 18.5 dB, and a bandwidth of 9.5 nm is achieved by a large corrugation width of 150 nm. The insertion loss at the drop port is only 0.8 dB, and the extinction ratio is up to 24 dB at the through port.

Silicon band-rejection and band-pass filter based on asymmetric Bragg sidewall gratings in a multimode waveguide.

A silicon photonic wire filter based on an asymmetric sidewall Bragg grating in a multimode silicon-on-insulator strip waveguide is demonstrated. The operating principle is based on the contra-directional coupling between the transverse electric fundamental (TE0) and first-order (TE1) modes, which is enabled by the asymmetric spatially periodic refractive-index perturbations. An asymmetric Y-junction is cascaded at the input port of the filter so as to drop the Bragg reflection. Compared with conventional Bragg grating-based filters, this device eliminates the back reflection at the input port and the 6 dB inherent insertion loss at the drop port; moreover, a narrow 3 dB bandwidth can be obtained with a large critical dimension as a result of the weak coupling strength between the TE0 and TE1 modes inside the multimode waveguide. Experimental results show that a bandwidth of ∼2.8 nm is achieved by a large corrugation width of 150 nm. The insertion loss at the drop port is -2.1 dB, and the extinction ratio is -33 dB at the through port.

On-chip microwave signal generation based on a silicon microring modulator.

A photonic-assisted microwave signal generator based on a silicon microring modulator is demonstrated. The microring cavity incorporates an embedded PN junction that enables a microwave signal to modulate the lightwave circling inside. The DC component of the modulated light is trapped in the cavity, while the high-order sideband components are able to exit the cavity and then generate microwave signals at new frequencies in a photodetector. In our proof-of-concept experiment, a 10 GHz microwave signal is converted to a 20 GHz signal in the optical domain with an electrical harmonic suppression ratio of 22 dB. An analytic model is also established to explain the operation mechanism, which agrees well with the measured data.

Dual function of mitochondrial Nm23-H4 protein in phosphotransfer and intermembrane lipid transfer: a cardiolipin-dependent switch.

The nucleoside diphosphate kinase Nm23-H4/NDPK-D forms symmetrical hexameric complexes in the mitochondrial intermembrane space with phosphotransfer activity using mitochondrial ATP to regenerate nucleoside triphosphates. We demonstrate the complex formation between Nm23-H4 and mitochondrial GTPase OPA1 in rat liver, suggesting its involvement in local and direct GTP delivery. Similar to OPA1, Nm23-H4 is further known to strongly bind in vitro to anionic phospholipids, mainly cardiolipin, and in vivo to the inner mitochondrial membrane. We show here that such protein-lipid complexes inhibit nucleoside diphosphate kinase activity but are necessary for another function of Nm23-H4, selective intermembrane lipid transfer. Mitochondrial lipid distribution was analyzed by liquid chromatography-mass spectrometry using HeLa cells expressing either wild-type Nm23-H4 or a membrane binding-deficient mutant at a site predicted based on molecular modeling to be crucial for cardiolipin binding and transfer mechanism. We found that wild type, but not the mutant enzyme, selectively increased the content of cardiolipin in the outer mitochondrial membrane, but the distribution of other more abundant phospholipids (e.g. phosphatidylcholine) remained unchanged. HeLa cells expressing the wild-type enzyme showed increased accumulation of Bax in mitochondria and were sensitized to rotenone-induced apoptosis as revealed by stimulated release of cytochrome c into the cytosol, elevated caspase 3/7 activity, and increased annexin V binding. Based on these data and molecular modeling, we propose that Nm23-H4 acts as a lipid-dependent mitochondrial switch with dual function in phosphotransfer serving local GTP supply and cardiolipin transfer for apoptotic signaling and putative other functions.

[Radiographic study of relationship between medial cuneiform obliquity and simple hallux valgus].

OBJECTIVE: To investigate the relationship between hallux valgus and the indicators associated with medial cuneiform obliquity measured on feet weight-bearing anteroposterior X-ray films. METHODS: Based on the feet weight-bearing anteroposterior X-ray films taken between January 2018 and February 2021 and met the criteria, the hallux valgus angle (HVA), intermetatarsal angle (IMA), metatarsus adductus angle (MAA), metatarsus cuneiform angle (MCA), distal medial cuneiform angle (DMCA), and proximal metatarsal articular angle (PMAA) were measured and the morphology of the first tarsometatarsal (TMT) were recorded. According to the HVA, the X-ray films were divided into normal group (HVA<15°) and hallux valgus group (HVA≥15°). The gender, age, sides, IMA, MAA, MCA, DMCA, PMAA, and the morphology of TMT were compared between groups. The influencing factors of HVA and IMA were analyzed by multivariate linear regression analysis. RESULTS: X-ray films of 534 patients (679 feet) met the selection criteria and were included in the study. There were 220 males and 314 females, with an average age of 36 years (mean, 18-82 years). There were 154 cases (168 feet) in the normal group and 403 cases (511 feet) in the hallux valgus group. There were significant differences in gender and age between groups ( P<0.05), and no significant difference in the side ( P>0.05). The IMA, MAA, and MCA in the hallux valgus group were significantly bigger than those in the normal group ( P<0.05); the difference in DMCA between the two groups was not significant ( P>0.05). The TMT morphology of the two groups was mainly curved, and the difference in morphology classification was not significant ( P>0.05). PMAA measurement showed that there were 3 kinds of metatarsal shapes: adductive metatarsal, neutral metatarsal, and abductive metatarsal, the difference in metatarsal shapes between groups was not significant ( P>0.05). The PMAA of abductive metatarsal was significantly bigger in normal group than in hallux valgus group ( P<0.05), there was no significant difference in PMAA of adductive metatarsal between groups ( P>0.05). Multivariate linear regression analysis showed that age, MCA, and DMCA were the influencing factors of HVA ( P<0.05), and age, MAA, MCA, and DMCA were the influencing factors of IMA ( P<0.05). CONCLUSION: The medial cuneiform obliquity is relatively constant and the DMCA can not be used as the characteristic angle to quantify hallux valgus. The morphology of TMT has no relationship with hallux valgus, while MAA, MCA, and PMAA are all factors to be considered, and MCA can be used as the characteristic angle to quantify hallux valgus.

Are mitochondrial reactive oxygen species required for autophagy?

Reactive oxygen species (ROS) are said to participate in the autophagy signaling. Supporting evidence is obscured by interference of autophagy and apoptosis, whereby the latter heavily relies on ROS signaling. To dissect autophagy from apoptosis we knocked down expression of cytochrome c, the key component of mitochondria-dependent apoptosis, in HeLa cells using shRNA. In cytochrome c deficient HeLa1.2 cells, electron transport was compromised due to the lack of electron shuttle between mitochondrial respiratory complexes III and IV. A rapid and robust LC3-I/II conversion and mitochondria degradation were observed in HeLa1.2 cells treated with staurosporine (STS). Neither generation of superoxide nor accumulation of H(2)O(2) was detected in STS-treated HeLa1.2 cells. A membrane permeable antioxidant, PEG-SOD, plus catalase exerted no effect on STS-induced LC3-I/II conversion and mitochondria degradation. Further, STS caused autophagy in mitochondria DNA-deficient ρ° HeLa1.2 cells in which both electron transport and ROS generation were completely disrupted. Counter to the widespread view, we conclude that mitochondrial ROS are not required for the induction of autophagy.

The cyclooxygenase site, but not the peroxidase site of cyclooxygenase-2 is required for neurotoxicity in hypoxic and ischemic injury.

Cyclooxygenase-2 (COX-2) activity has been implicated in the pathogenesis of ischemic injury, but the exact mechanisms responsible for its toxicity remain unclear. Infection of primary neurons with an adenovirus expressing wild type (WT) COX-2 increased the susceptibility of neurons to hypoxia. Infection with an adenoviral vector expressing COX-2 with a mutation at the cyclooxygenase site did not increase susceptibility to hypoxia, whereas over-expression of COX-2 with a mutation in the peroxidase site produced similar susceptibility to hypoxia as WT COX-2. Primary neuronal cultures obtained from transgenic mice bearing a mutation in the COX-2 cylooxygenase site were protected from hypoxia. Mice with a mutation in the cyclooxygenase site had smaller infarctions 24 h after 70 min of middle cerebral artery occlusion than WT control mice. COX-2 activity had no effect on the formation of protein carbonyls. Ascorbate radicals were detected by electron paramagnetic resonance as a product of recombinant COX-2 activity and were blocked by COX-2 inhibitors. Similarly, formation of ascorbate radicals was inhibited in the presence of COX-2 inhibitors and in homogenates obtained from COX-2 null mice. Taken together, these results indicate that the cyclooxygenase activity of COX-2 is necessary to exacerbate neuronal hypoxia/ischemia injury rather than the peroxidase activity of the enzyme.

Protection of normal brain cells from γ-irradiation-induced apoptosis by a mitochondria-targeted triphenyl-phosphonium-nitroxide: a possible utility in glioblastoma therapy.

Glioblastoma multiforme is the most frequent and aggressive primary brain tumor. A strong rationale to identify innovative approaches to treat these tumors is required since treatment failures result in local recurrences and median survivals range from 9 to 12 months. Glioma cells are reported to have less mitochondrial content compared to adjacent normal brain cells. Based on this difference, we suggest a new strategy, utilizing protection of normal brain cells by mitochondria-targeted electron scavengers and antioxidants-nitroxides-thus allowing for the escalation of the radiation doses. In this paper, we report that a conjugate of nitroxide with a hydrophobic cation, triphenyl-phosphonium (TPEY-Tempo), significantly protected brain endothelial cells from γ-irradiation-induced apoptosis while radiosensitizing brain tumor cells. Thus, TPEY-Tempo may be a promising adjunct in the treatment of glioblastoma with the potential to not only prolong survival but also to maintain quality of life and reduce treatment toxicity.

Synthetic protection short interfering RNA screen reveals glyburide as a novel radioprotector.

To assist in screening existing drugs for use as potential radioprotectors, we used a human unbiased 16,560 short interfering RNA (siRNA) library targeting the druggable genome. We performed a synthetic protection screen that was designed to identify genes that, when silenced, protected human glioblastoma T98G cells from gamma-radiation-induced cell death. We identified 116 candidate protective genes, then identified 10 small molecule inhibitors of 13 of these candidate gene products and tested their radioprotective effects. Glyburide, a clinically used second-generation hypoglycemic drug, effectively decreased radiation-induced cell death in several cell lines including T98G, glioblastoma U-87 MG, and normal lung epithelial BEAS-2B and in primary cultures of astrocytes. Glyburide significantly increased the survival of 32D cl3 murine hematopoietic progenitor cells when administrated before irradiation. Glyburide was radioprotective in vivo (90% of C57BL/6NHsd female mice pretreated with 10 mg/kg glyburide survived 9.5 Gy total-body irradiation compared to 42% of irradiated controls, P = 0.0249). These results demonstrate the power of unbiased siRNA synthetic protection screening with a druggable genome library to identify new radioprotectors.

Mass-spectrometric characterization of phospholipids and their primary peroxidation products in rat cortical neurons during staurosporine-induced apoptosis.

The molecular diversity of phospholipids is essential for their structural and signaling functions in cell membranes. In the current work, we present, the results of mass spectrometric characterization of individual molecular species in major classes of phospholipids -- phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn), phosphatidylserine (PtdSer), phosphatidylinositol (PtdIns), sphingomyelin (CerPCho), and cardiolipin (Ptd(2)Gro) -- and their oxidation products during apoptosis induced in neurons by staurosporine (STS). The diversity of molecular species of phospholipids in rat cortical neurons followed the order Ptd(2)Gro > PtdEtn >> PtdCho >> PtdSer > PtdIns > CerPCho. The number of polyunsaturated oxidizable species decreased in the order Ptd(2)Gro >> PtdEtn > PtdCho > PtdSer > PtdIns > CerPCho. Thus a relatively minor class of phospholipids, Ptd(2)Gro, was represented in cortical neurons by the greatest variety of both total and peroxidizable molecular species. Quantitative fluorescence HPLC analysis employed to assess the oxidation of different classes of phospholipids in neuronal cells during intrinsic apoptosis induced by STS revealed that three anionic phospholipids -- Ptd(2)Gro >> PtdSer > PtdIns -- underwent robust oxidation. No significant oxidation in the most dominant phospholipid classes -- PtdCho and PtdEtn -- was detected. MS-studies revealed the presence of hydroxy-, hydroperoxy- as well as hydroxy-/hydroperoxy-species of Ptd(2)Gro, PtdSer, and PtdIns. Experiments in model systems where total cortex Ptd(2)Gro and PtdSer fractions were incubated in the presence of cytochrome c (cyt c) and H(2)O(2), confirmed that molecular identities of the products formed were similar to the ones generated during STS-induced neuronal apoptosis. The temporal sequence of biomarkers of STS-induced apoptosis and phospholipid peroxidation combined with recently demonstrated redox catalytic properties of cyt c realized through its interactions with Ptd(2)Gro and PtdSer suggest that cyt c acts as a catalyst of selective peroxidation of anionic phospholipids yielding Ptd(2)Gro and PtdSer peroxidation products. These oxidation products participate in mitochondrial membrane permeability transition and in PtdSer externalization leading to recognition and uptake of apoptotic cells by professional phagocytes.

Cardiolipin deficiency leads to decreased cardiolipin peroxidation and increased resistance of cells to apoptosis.

Cardiolipin (CL), a unique mitochondrial phospholipid synthesized by CL synthase (CLS), plays important, yet not fully understood, roles in mitochondria-dependent apoptosis. We manipulated CL levels in HeLa cells by knocking down CLS using RNA interference and selected a clone of CL-deficient cells with approximately 45% of its normal content. ESI-MS analysis showed that the CL molecular species were the same in CL-deficient and CL-sufficient cells. CL deficiency did not change mitochondrial functions (membrane potential, reactive oxygen species generation, cellular ATP levels) but conferred resistance to apoptosis induced by actinomycin D (ActD), rotenone, or gamma-irradiation. During ActD-induced apoptosis, decreased CL peroxidation along with suppressed cytochrome (cyt) c release was observed in CL-deficient cells, whereas Bax translocation to mitochondria remained similar to that in CL-sufficient HeLa cells. The amounts of loosely bound cyt c (releasable under high ionic strength conditions) were the same in CL-deficient and CL-sufficient cells. Given that CL peroxidation during apoptosis is catalyzed by CL/cyt c complexes and CL oxidation products are essential for cyt c release from mitochondria, our results suggest that CL deficiency prevents adequate assembly of productive CL/cyt c complexes and CL peroxidation, resulting in increased resistance to apoptosis.

Interplay between bax, reactive oxygen species production, and cardiolipin oxidation during apoptosis.

Bax/Bak activation and cardiolipin peroxidation are essential for cytochrome c release during apoptosis, yet, the link between them remains elusive. We report that sequence of events after exposure of mouse embryonic fibroblast (MEF) cells to actinomycin D followed the order: Bax translocation-->superoxide production-->cardiolipin peroxidation. Genetic ablation of Bax/Bak inhibited actinomycin D induced superoxide production and cardiolipin peroxidation. Rotenone caused robust superoxide generation but did not trigger cardiolipin peroxidation in Bax/Bak double knockout MEF cells. This suggests that, in addition to participating in ROS generation, Bax/Bak play another specific role in cardiolipin oxidation. In isolated mitochondria, recombinant Bax enhanced succinate induced cardiolipin oxidation and cytochrome c release. Mitochondrial peroxidase activity, likely involved in cardiolipin peroxidation, was enhanced upon incubation with recombinant Bax. Thus, cardiolipin peroxidation may be causatively and time-dependently related to Bax/Bak effects on ROS generation and peroxidase activation of cytochrome c.

A mitochondria-targeted nitroxide/hemigramicidin S conjugate protects mouse embryonic cells against gamma irradiation.

PURPOSE: To evaluate the in vitro radioprotective effect of the mitochondria-targeted hemigramicidin S-conjugated 4-amino-2,2,6,6-tetramethyl-piperidine-N-oxyl (hemi-GS-TEMPO) 5-125 in gamma-irradiated mouse embryonic cells and adenovirus-12 SV40 hybrid virus transformed human bronchial epithelial cells BEAS-2B and explore the mechanisms involved in its radioprotective effect. METHODS AND MATERIALS: Cells were incubated with 5-125 before (10 minutes) or after (1 hour) gamma-irradiation. Superoxide generation was determined by using dihydroethidium assay, and lipid oxidation was quantitated by using a fluorescence high-performance liquid chromatography-based Amplex Red assay. Apoptosis was characterized by evaluating the accumulation of cytochrome c in the cytosol and externalization of phosphatidylserine on the cell surface. Cell survival was measured by means of a clonogenic assay. RESULTS: Treatment (before and after irradiation) of cells with 5-125 at low concentrations (5, 10, and 20 mum) effectively suppressed gamma-irradiation-induced superoxide generation, cardiolipin oxidation, and delayed irradiation-induced apoptosis, evaluated by using cytochrome c release and phosphatidylserine externalization. Importantly, treatment with 5-125 increased the clonogenic survival rate of gamma-irradiated cells. In addition, 5-125 enhanced and prolonged gamma-irradiation-induced G(2)/M phase arrest. CONCLUSIONS: Radioprotection/mitigation by hemi-GS-TEMPO likely is caused by its ability to act as an electron scavenger and prevent superoxide generation, attenuate cardiolipin oxidation in mitochondria, and hence prevent the release of proapoptotic factors from mitochondria. Other mechanisms, including cell-cycle arrest at the G(2)/M phase, may contribute to the protection.