CAR-T Cells in the Treatment of Ovarian Cancer: A Promising Cell Therapy.

Ovarian cancer (OC) is among the most common gynecologic malignancies with a poor prognosis and a high mortality rate. Most patients are diagnosed at an advanced stage (stage III or IV), with 5-year survival rates ranging from 25% to 47% worldwide. Surgical resection and first-line chemotherapy are the main treatment modalities for OC. However, patients usually relapse within a few years of initial treatment due to resistance to chemotherapy. Cell-based therapies, particularly adoptive T-cell therapy and chimeric antigen receptor T (CAR-T) cell therapy, represent an alternative immunotherapy approach with great potential for hematologic malignancies. However, the use of CAR-T-cell therapy for the treatment of OC is still associated with several difficulties. In this review, we comprehensively discuss recent innovations in CAR-T-cell engineering to improve clinical efficacy, as well as strategies to overcome the limitations of CAR-T-cell therapy in OC.

Congenital dysfibrinogenemia misdiagnosed and inappropriately treated as acute fatty liver in pregnancy: A case report and review of literature.

BACKGROUND: The purpose of this study was to report the rare case of a pregnant woman with congenital dysfibrinogenemia (CD) misdiagnosed as acute fatty liver. She was treated according to the principles of acute fatty liver but achieved good clinical results. CASE SUMMARY: A 30-year-old woman presented with 39 (6/7) wk of menopause and 6 h of irregular abdominal pain and attended our hospital. Emergency surgery was performed due to fetal distress. Postoperative management followed the treatment principle of acute fatty liver. DNA sequencing was carried out on the pregnant woman and her pedigree. Coagulation values of the patient on admission were prothrombin time 33.7 s, activated partial thromboplastin time 60.4 s, thrombin time 45.2 s, and fibrinogen 0.60 g/L. DNA sequencing results showed that the woman carried a pathogenic heterozygous variation of the fibrinogen alpha chain gene (FGA), which is closely related to hereditary fibrinogen abnormality, and the mutation site was located in p.R350H. After a follow-up period of 12 mo, the mother and her newborn had a good prognosis without bleeding or thrombosis. CONCLUSION: Pregnant women with CD may have atypical symptoms, which can easily lead to misdiagnosis. In addition, treatment can be attempted according to the principles of acute fatty liver management. This rare pregnant patient with CD was caused by a novel FGA (p.R350H) gene mutation.

MutL homolog 1 germline mutation c.(453+1_454-1)_(545+1_546-1)del identified in lynch syndrome: A case report and review of literature.

BACKGROUND: Lynch syndrome (LS) is an autosomal dominant hereditary disorder because of germline mutations in DNA mismatch repair genes, such as MutL homolog 1 (MLH1), PMS1 homolog 2, MutS homolog 2, and MutS homolog 6. Gene mutations could make individuals and their families more susceptible to experiencing various malignant tumors. In Chinese, MLH1 germline mutation c.(453+1_454-1)_(545+1_546-1)del-related LS has been infrequently reported. Therefore, we report a rare LS patient with colorectal and endometrioid adenocarcinoma and describe her pedigree characteristics. CASE SUMMARY: A 57-year-old female patient complained of irregular postmenopausal vaginal bleeding for 6 mo. She was diagnosed with LS, colonic malignancy, endometrioid adenocarcinoma, secondary fallopian tube malignancy, and intermyometrial leiomyomas. Then, she was treated by abdominal hysterectomy, bilateral oviduct oophorectomy, and sentinel lymph node resection. Genetic testing was performed using next-generation sequencing technology to detect the causative genetic mutations. Moreover, all her family members were offered a free genetic test, but no one accepted it. CONCLUSION: No tumor relapse or metastasis was found in the patient during the 30-mo follow-up period. The genetic panel sequencing showed a novel pathogenic germline mutation in MLH1, c.(453+1_454-1)_(545+1_546-1)del, for LS. Moreover, cancer genetic counseling and testing are still in the initial development state in China, and maybe face numerous challenges in the further.

Facile Strategy for Efficient Charge Separation and High Photoactivity of Mixed-Linker MOFs.

Two new sets of UiO-Zr metal-organic framework (MOF) bearing mixed linkers BDC-(SCH3)2 and BDC-(SOCH3)2 that have different band gaps and edges were prepared through post oxidation and direct methods, namely, UiO-66-(SCH3)2-xh (x = 4, 9, 12 oxidation hours) and UiO-66-(SOCH3)x(SCH3)2-x (x = 0, 0.4, 0.6, 2), respectively. These composites with stoichiometric components were fully characterized via proton nuclear magnetic resonance (1H NMR) spectroscopy, powder X-ray diffraction (PXRD), transmission electron microscopy (TEM), Fourier-transform infrared (FT-IR) spectra, Brunauer-Emmett-Teller (BET), photo electrochemical measurements, and femtosecond transient absorption (fs-TA) spectroscopy. The structure, electronic property, and photoresponsive and catalytic ability as the functions of the molar ratio of linkers and the synthetic protocol were first investigated. The mixed-linker UiO-66-(SCH3)2-xh and UiO-66-(SOCH3)x(SCH3)2-x exhibited improved performances as compared to the UiO-66-(SCH3)2 and UiO-66-(SOCH3)2 possessing neat linkers only. Their photo response and catalytic activity varied with different linker ratios. For UiO-66-(SCH3)2-xh, the performance increased with the increasing linker BDC-(SOCH3)2 ratio upon oxidation but reached the highest as the BDC-(SOCH3)2 being of 24.4% in UiO-66-(SCH3)2-9h. In comparison, the best photocurrent (80.74 uA/cm-2) and the highest H2 generation rate (2018.8 µmol g-1 h-1) (λ > 400 nm) in UiO-66-(SCH3)2-9h are about twice those of UiO-66-(SOCH3)0.4(SCH3)1.6 obtained by direct synthesis, although the linker BDC-(SOCH3)2 ratio of those two composites is almost the same (24.4% vs 23.9%). Recorded shorter lifetime and higher charge separation efficiency of the former than those of the latter suggest the postsynthetic protocol as the efficient method for achieving the mixed-liner-MOF-based photocatalyst with high performance. A new type-II tailored homojunction is proposed in these mixed-linker MOFs for their efficient charge separation and improved activity.

ortho-Heterofluorene perylenediimides: synthesis, photophysical, and exciton dynamic properties.

Previous studies suggest the perylenediimide (PDI) triplet excited state (T1) have been accessible only through bimolecular sensitization, the internal heavy-atom effect or a sophisticated cascade of nonradiative processes. Here, we designed heavy-atom-free PDIs to prompt the Tn ← S1 intersystem crossing (ISC) by introducing electron donating heterofluorene groups at the head positions of the electron-deficient PDI core. We obtained relatively high ISC efficiency up to 92% yield. Furthermore, promptly generated PDI triplets can sensitize the molecular oxygen quantitatively to yield 1O2, with singlet oxygen generation efficiencies (ΦΔ) near to unity. These results further suggest that the ISC process of PDIs can be enhanced through the intramolecular charge transfer (ICT) interaction, providing guidelines for developing triplet-generating PDIs and related rylene diimides for optoelectronic applications.

Heterovalent-Doping-Enabled Efficient Dopant Luminescence and Controllable Electronic Impurity Via a New Strategy of Preparing II-VI Nanocrystals.

Substitutional heterovalent doping represents an effective method to control the optical and electronic properties of nanocrystals (NCs). Highly monodisperse II-VI NCs with deep substitutional dopants are presented. The NCs exhibit stable, dominant, and strong dopant fluorescence, and control over n- and p-type electronic impurities is achieved. Large-scale, bottom-up superlattices of the NCs will speed up their application in electronic devices.

Role of ligand-to-metal charge transfer state in nontriplet photosensitization of luminescent europium complex.

We have investigated, by means of steady-state and time-resolved optical spectroscopies, the excited-state dynamics of the luminescent europium complex Eu(III)(tta)(3)dpbt (tta = henoyltrifluoroacetonate; dbpt = 2-(N,N-diethylanilin-4-yl)-4,6-bis(3,5-dimethylpyrazol-1-yl)-1,3,5-triazine) with Gd(III)(tta)(3)dpbt and Tb(III)(tta)(3)dpbt as the reference complexes that cannot be photosensitized. In the Eu(III)(tta)(3)dpbt complex, the ligand dpbt exhibited biphasic fluorescence decay kinetics; the faster component (decay time constant, 8.5 ps) is ascribed to the rapid conversion of the lowest-lying singlet excited state of dpbt (S(1) or (1)dpbt*) to a ligand-to-metal charge transfer singlet state of the complex ((1)LMCT*), whereas the slower one (1.8 ns) is shown by temperature-dependent luminescence spectroscopy to be delayed fluorescence due to the LMCT-to-dpbt backward energy transfer and represents the time scale of efficient excitation energy flow from the (1)LMCT* state to the (5)D(1) state of Eu(III). On the basis of the spectroscopic results of the Ln(III)(tta)(3)dpbt complexes (Ln = Eu, Gd, and Tb), the crucial role of the (1)LMCT* state in photosensitization of the Eu(III)(tta)(3)dpbt complex is established, and a LMCT-mediated nontriplet sensitization mechanism is proposed, which is advantageous in high efficiency and low excitation photon energy as well as in low susceptibility against oxygen quenching.

Excitation dynamics of two spectral forms of the core complexes from photosynthetic bacterium Thermochromatium tepidum.

The intact core antenna-reaction center (LH1-RC) core complex of thermophilic photosynthetic bacterium Thermochromatium (Tch.) tepidum is peculiar in its long-wavelength LH1-Q(y) absorption (915 nm). We have attempted comparative studies on the excitation dynamics of bacteriochlorophyll (BChl) and carotenoid (Car) between the intact core complex and the EDTA-treated one with the Q(y) absorption at 889 nm. For both spectral forms, the overall Car-to-BChl excitation energy transfer efficiency is determined to be approximately 20%, which is considerably lower than the reported values, e.g., approximately 35%, for other photosynthetic purple bacteria containing the same kind of Car (spirilloxanthin). The RC trapping time constants are found to be 50 approximately 60 ps (170 approximately 200 ps) for RC in open (closed) state irrespective to the spectral forms and the wavelengths of Q(y) excitation. Despite the low-energy LH1-Q(y) absorption, the RC trapping time are comparable to those reported for other photosynthetic bacteria with normal LH1-Q(y) absorption at 880 nm. Selective excitation to Car results in distinct differences in the Q(y)-bleaching dynamics between the two different spectral forms. This, together with the Car band-shift signals in response to Q(y) excitation, reveals the presence of two major groups of BChls in the LH1 of Tch. tepidum with a spectral heterogeneity of approximately 240 cm(-1), as well as an alteration in BChl-Car geometry in the 889-nm preparation with respect to the native one.

Interplay between the keto defect and the interchain interaction on the green emission of fluorene-based polymer.

To investigate the interplay between on-chain keto defect and interchain interaction and its consequence on the blue emission of polyfluorene (PF), first- to third-generation dendronized PFs as well as single-fluorenone-unit doped PF (PFN), synthesized by Suzuki polycondensation, were used as model compounds for steady-state and picosecond time-resolved photoluminescence (PL) spectroscopic studies. For PF film, the broad-band green emission did not appear, although severe interchain interaction was observed. For PFN film, the green emission that peaked at approximately 540 nm decayed in a multiphasic manner, suggesting significant heterogeneity in the excitation migration toward the keto center. To further examine the interplay effect, a series of novel dendronized-PF/PFN blend films in a molar ratio of 40:1 fluorene-to-fluorenone unit were studied. With reference to pure PFN film, those of the green emission of the blends showed strong dependence on the order of dendronization, that is, a higher generation resulted in a shorter-lived green emission. These observations are discussed in terms of interchain and/or intersegment interactions between the fluorene segments and the keto defect. It is concluded that the keto unit and the keto-centered, interchain aggregation lead to severe color degradation in a synergistic manner, and that dendronization can effectively minimize the undesirable green emission.

Mechanism of radical cation formation from the excited states of zeaxanthin and astaxanthin in chloroform.

The C-40 xanthophylls zeaxanthin and astaxanthin were confirmed to form radical cations, Car.+, in the electron-accepting solvent chloroform by direct excitation using subpicosecond time-resolved absorption spectroscopy in combination with spectroelectrochemical determination of the near-infrared absorption of Car.+. For the singlets, the S2(1B(u+) state and most likely the S(x)(3A(g)-) state directly eject electrons to chloroform leading to the rapid formation of Car.+ on a timescale of approximately 100 fs; the lowest-lying S1(2A(g)-) state, however, remains inactive. Standard reduction potential for Car.+ was determined by cyclic voltametry to have the value 0.63 V for zeaxanthin and 0.75 V for astaxanthin from which excited state potentials were calculated, which confirmed the reactivity toward radical cation formation. On the other hand, Car.+ formation from the lowest triplet excited state T1 populated through anthracene sensitization is mediated by a precursor suggested to be a solute-solvent complex detected with broad near-infrared absorption to the shorter wavelength side of the characteristic Car.+ absorption. However, ground state carotenoids are able to react with a secondary solvent radical to yield Car.+, a process occurring within 16 micros for zeaxanthin and within 21 mus for astaxanthin. Among the two xanthophylls together with lycopene and beta-carotene, all having 11 conjugated double bonds, zeaxanthin ranks with the highest reactivity in forming Car.+ from either the S2(1B(u+)) or the ground state. The effects of substituent groups on the reactivity are discussed.

Ultrafast carotenoid-to-chlorophyll singlet energy transfer in the cytochrome b6f complex from Bryopsis corticulans.

Ultrafast carotenoid-to-chlorophyll (Car-to-Chl) singlet excitation energy transfer in the cytochrome b(6)f (Cyt b(6)f) complex from Bryopsis corticulans is investigated by the use of femtosecond time-resolved absorption spectroscopy. For all-trans-alpha-carotene free in n-hexane, the lifetimes of the two low-lying singlet excited states, S(1)(2A(g)(-)) and S(2)(1B(u)(+)), are determined to be 14.3 +/- 0.4 ps and 230 +/- 10 fs, respectively. For the Cyt b(6)f complex, to which 9-cis-alpha-carotene is bound, the lifetime of the S(1)(2A(g)(-)) state remains unchanged, whereas that of the S(2)(1B(u)(+)) state is significantly reduced. In addition, a decay-to-rise correlation between the excited-state dynamics of alpha-carotene and Chl a is clearly observed. This spectroscopic evidence proves that the S(2)(1B(u)(+)) state is able to transfer electronic excitations to the Q(x) state of Chl a, whereas the S(1)(2A(g)(-)) state remains inactive. The time constant and the partial efficiency of the energy transfer are determined to be 240 +/- 40 fs and (49 +/- 4)%, respectively, which supports the overall efficiency of 24% determined with steady-state fluorescence spectroscopy. A scheme of the alpha-carotene-to-Chl a singlet energy transfer is proposed based on the excited-state dynamics of the pigments.

Protein structural deformation induced lifetime shortening of photosynthetic bacteria light-harvesting complex LH2 excited state.

Photosynthetic bacterial light-harvesting antenna complex LH2 was immobilized on the surface of TiO(2) nanoparticles in the colloidal solution. The LH2/TiO(2) assembly was investigated by the time-resolved spectroscopic methods. The excited-state lifetimes for carotenoid-containing and carotenoidless LH2 have been measured, showing a decrease in the excited-state lifetime of B850 when LH2 was immobilized on TiO(2). The possibility that the decrease of the LH2 excited-state lifetime being caused by an interfacial electron transfer reaction between B850 and the TiO(2) nanoparticle was precluded experimentally. We proposed that the observed change in the photophysical properties of LH2 when assembled onto TiO(2) nanoparticles is arising from the interfacial-interaction-induced structural deformation of the LH2 complex deviating from an ellipse of less eccentric to a more eccentric ellipse, and the observed phenomenon can be accounted by an elliptical exciton model. Experiment by using photoinactive SiO(2) nanoparticle in place of TiO(2) and core complex LH1 instead of LH2 provide further evidence to the proposed mechanism.

Radical cation generation from singlet and triplet excited states of all-trans-lycopene in chloroform.

On direct photoexcitation, subpicosecond time-resolved absorption spectroscopy revealed that the 1B(u)-type singlet excited state of all-trans-lycopene in chloroform was about seven times more efficient than all-trans-beta-carotene in generating the radical cation. The time constant of radical cation generation from the 1B(u)-type state was found to be approximately 0.14 ps, a value that was comparable for the two carotenoids. On anthracene-sensitized triplet excitation, radical cation generation was found to be much less efficient for lycopene than for beta-carotene. A slow rising phase (20-30 micros) in the bleaching of ground-state absorption was common for both lycopene and beta-carotene in chloroform and was ascribed to an efficient secondary reaction with a solvent radical leading to the formation of carotenoid radical cations. The reverse ordering in the tendency of the excited states of different multiplicities for the two carotenoids to generate radical cations is discussed in relation to the two carotenoids as scavengers of free radicals.

Triplet Excitation Transfer between Carotenoids in the LH2 Complex from Photosynthetic Bacterium Rhodopseudomonas palustris.

We have studied, by means of sub-microsecond time-resolved absorption spectroscopy, the triplet-excited state dynamics of carotenoids (Cars) in the intermediate-light adapted LH2 complex (ML-LH2) from Rhodopseudomonas palustris containing Cars with different numbers of conjugated double bonds. Following pulsed photo-excitation at 590 nm at room temperature, rapid spectral equilibration was observed either as a red shift of the isosbestic wavelength on a time scale of 0.6-1.0 mus, or as a fast decay in the shorter-wavelength side of the T(n)<--T(1) absorption of Cars with a time constant of 0.5-0.8 mus. Two major spectral components assignable to Cars with 11 and 12 conjugated double bonds were identified. The equilibration was not observed in the ML-LH2 at 77 K, or in the LH2 complex from Rhodobacter sphaeroides G1C containing a single type of Car. The unique spectral equilibration was ascribed to temperature-dependent triplet excitation transfer among different Car compositions. The results suggest that Cars of 11 and 12 conjugated bonds, both in close proximity of BChls, may coexist in an alpha,beta-subunit of the ML-LH2 complex.