Consecutive palmitoylation and phosphorylation orchestrates NLRP3 membrane trafficking and inflammasome activation.

NLRP3 inflammasome activation, essential for cytokine secretion and pyroptosis in response to diverse stimuli, is closely associated with various diseases. Upon stimulation, NLRP3 undergoes subcellular membrane trafficking and conformational rearrangements, preparing itself for inflammasome assembly at the microtubule-organizing center (MTOC). Here, we elucidate an orchestrated mechanism underlying these ordered processes using human and murine cells. Specifically, NLRP3 undergoes palmitoylation at two sites by palmitoyl transferase zDHHC1, facilitating its trafficking between subcellular membranes, including the mitochondria, trans-Golgi network (TGN), and endosome. This dynamic trafficking culminates in the localization of NLRP3 to the MTOC, where LATS1/2, pre-recruited to MTOC during priming, phosphorylates NLRP3 to further facilitate its interaction with NIMA-related kinase 7 (NEK7), ultimately leading to full NLRP3 activation. Consistently, Zdhhc1-deficiency mitigated LPS-induced inflammation and conferred protection against mortality in mice. Altogether, our findings provide valuable insights into the regulation of NLRP3 membrane trafficking and inflammasome activation, governed by palmitoylation and phosphorylation events.

Prediction of the treatment effect of FLASH radiotherapy with synchrotron radiation from the Circular Electron-Positron Collider (CEPC).

The Circular Electron-Positron Collider (CEPC) in China can also work as an excellent powerful synchrotron light source, which can generate high-quality synchrotron radiation. This synchrotron radiation has potential advantages in the medical field as it has a broad spectrum, with energies ranging from visible light to X-rays used in conventional radiotherapy, up to several megaelectronvolts. FLASH radiotherapy is one of the most advanced radiotherapy modalities. It is a radiotherapy method that uses ultra-high dose rate irradiation to achieve the treatment dose in an instant; the ultra-high dose rate used is generally greater than 40 Gy s-1, and this type of radiotherapy can protect normal tissues well. In this paper, the treatment effect of CEPC synchrotron radiation for FLASH radiotherapy was evaluated by simulation. First, a Geant4 simulation was used to build a synchrotron radiation radiotherapy beamline station, and then the dose rate that the CEPC can produce was calculated. A physicochemical model of radiotherapy response kinetics was then established, and a large number of radiotherapy experimental data were comprehensively used to fit and determine the functional relationship between the treatment effect, dose rate and dose. Finally, the macroscopic treatment effect of FLASH radiotherapy was predicted using CEPC synchrotron radiation through the dose rate and the above-mentioned functional relationship. The results show that the synchrotron radiation beam from the CEPC is one of the best beams for FLASH radiotherapy.

Sliced chaotic encrypted transmission scheme based on key masked distribution in a W-band millimeter-wave system.

In order to guarantee the information of the W-band wireless communication system from the physical layer, this paper proposes the sliced chaotic encrypted (SCE) transmission scheme based on key masked distribution (KMD). The scheme improves the security of free space communication in the W-band millimeter-wave wireless data transmission system. In this scheme, the key information is embedded into the random position of the ciphertext information, and then the ciphertext carrying the key information is encrypted by multi-dimensional chaos. Chaotic system 1 constructs a three-dimensional discrete chaotic map for implementing KMD. Chaotic system 2 constructs complex nonlinear dynamic behavior through the coupling of two neurons, and the masking factor generated is used to realize SCE. In this paper, the transmission of 16QAM signals in a 4.5 m W-band millimeter-wave wireless communication system with a rate of 40 Gb/s is proved by experiments, and the performance of the system is analyzed. When the input optical power is 5 dBm, the bit error rate (BER) of the legitimate encrypted receiver is 1.23 × 10-3. When the offset of chaotic sequence x and chaotic sequence y is 100, their BERs are more than 0.21. The key space of the chaotic system reaches 10192, which can effectively prevent illegal attacks and improve the security performance of the system. The experimental results show that the scheme can effectively distribute the keys and improve the security of the system. It has great application potential in the future of W-band millimeter-wave wireless secure communication.

Secure high-density constellation mapping OTFS modulation scheme with low PAPR.

In this paper, a secure orthogonal time-frequency space (OTFS) modulation transmission system based on 3D dense constellation mapping (DCM) geometric shaping is proposed, and a selective reduction amplitude algorithm (SRA) for DCM to reduce peak average power ratio (PAPR) is presented. The DCM is based on regular tetrahedron construction to improve its space utilization efficiency. The proposed SRA involves reducing high PAPRs transmitter and restoring them at the receiving end, which only requires an additional 0.57% of the total transmission capacity. The algorithm reduces PAPR while ensuring the bit error rate performance of the system, so it is suitable for systems that need to process large amounts of transmitted data quickly. By verifying the actual transmission performance on a 2 km of 7-core optical fiber transmission system, the optical transmission with a bit rate of 33.93Gb/s is achieved. The experimental results show that when the bit error rate (BER) reaches the 3.8×10-3 threshold, the OTFS system using DCM and SRA could improve the receiver sensitivity by 3.7 dB compared with the OTFS system using concentric cube mapping and SRA, and 2.7 dB compared with the OFDM system using DCM. After adding the SRA, the PAPR of the OTFS system is reduced by more than 2.2 dB. When the received optical power reaches near the bit error rate threshold, the SRA valid data can be fully recovered by optimizing the SRA.

Physical layer security scheme for key concealment and distribution based on carrier scrambling.

The purpose of this study is to present a physical layer security scheme for key concealment and distribution based on carrier scrambling. The three-dimensional (3D) Lorenz system is used to generate independent chaotic sequences that encrypt the information with bit, constellation and subcarrier. In order to realize the flexible distribution of the key and ensure its security, the key information is loaded into a specific subcarrier. While key subcarrier and the ciphertext subcarrier are scrambled simultaneously. The encrypted key position information is processed and transmitted in conjunction with the training sequence (TS) to facilitate demodulation by the legitimate receiver. The processed TS can accommodate up to 10 key position information, thereby demonstrating the scheme's exceptional scalability. Experimental results show that the proposed scheme can safely transmit 131.80 Gb/s Orthogonal frequency division multiplexing (OFDM) signals across 2 km 7-core fiber. Meanwhile, the scheme enables simultaneous flexible distribution and concealment of the key, thereby offering a promising solution for physical layer security.

Chaos key enhanced physical layer secure transmission method based on the convolutional long short-term memory neural network.

In this paper, we propose a method for training a key-enhanced chaotic sequence using the convolutional long short term memory neural network (CLSTM-NN) for secure transmission. This method can cope with the potential security risk posed by the degradation of chaotic dynamics when using chaotic model encryption in traditional secure transmissions. The simulation results show that the proposed method improves the key space by 1036 compared to traditional chaotic models, reaching 10241. The method was applied to orthogonal chirp division multiplexing (OCDM). To demonstrate the feasibility of the proposed scheme, we conducted transmission experiments of encrypted 16 quadrature amplitude modulation (QAM) OCDM signals at a speed of 53.25 Gb/s over a 2 km length of 7-core optical fiber and test different encryption schemes. After key enhancements, the overall number of keys in the system can increase from 18 to 105.The results show that there is no significant difference between the bit error rate (BER) performance of the encryption method proposed in this paper and the traditional encryption method. The maximum performance difference between the different systems does not exceed 1 dBm. This fact proves the feasibility of the proposed scheme and provides new ideas for the next generation of secure transmission.

Highly secure non-orthogonal multiple access based on key accompanying transmission in training sequence.

This paper proposes a high-security chaotic encrypted power sparse coding division (CE-PSCD) scheme for 7-core fiber based on non-orthogonal multiple access (NOMA) technology. The method utilizes power multiplexing to realize parallel transmission of two signals. Joint encryption of the four-dimensional region is realized using constellation mapping encryption, carrier frequency encryption, symbol scrambling, and sparse code scrambling. What we believe to be a new dimension for encryption of autonomously designed sparse codes is proposed. Meanwhile, we hide the chaotic key in training sequence (TS) to realize the co-transmission of the key and the message. A 70 Gb/s CE-PSCD signal transmission over 2 km of 7-core fiber is demonstrated experimentally. At the limit of forward error correction (FEC) ∼3.8 × 10-3, the difference in the encrypted sensitivity among different users at the equal power level is 0.36 dB, which means that the fairness of users will not be destroyed. The key space can reach 10134, with a bit error rate (BER) of about 0.5 for brute-force cracking at illegal receivers. As long as the key bits in the hidden TS are wrong by one bit, the BER stays around 0.5. The results show no significant attenuation of the signal before and after encryption at either high or low power, verifying the high-security performance of our proposed scheme.

High spectral efficiency modulation scheme based on joint interaction of orthogonal compressed chirp division multiplexing and power superimposed code.

In this paper, we propose a high spectral efficiency modulation scheme based on joint interaction of orthogonal compressed chirp division multiplexing (OCCDM) and power superimposed code (PSC) under the intensity modulation and direct detection (IM/DD) system. OCCDM is a novel orthogonal chirp division multiplexing technology featuring spectral compression through the implementation of processing similar to a discrete Fourier transform, enhancing the spectral efficiency (SE) through bandwidth savings without loss of orthogonality of each chirp. Meanwhile, PSC technology enables multiple code words being transmitted superimposed on the same chirp. This technique involves allocating varying power levels to different users, thereby distinguishing them, increasing the transmission's net bit rate and substantially boosting the SE. The transmission has been performed experimentally using a 2 km 7-core fiber span. The impact of the above-mentioned technologies on the bit error rate (BER) performance is assessed in the power, frequency, and joint domain. The BER and enhancements in the SE can be balanced when the spectral bandwidth compression factor (α) and power distribution ratio are equal to 0.9 and 4, respectively. The observed outcome leads to the transmission's SE increase to more than double the baseline value, at 2.22 times. Based on the above analysis, we believe this structure is expected to become a potential for developing next-generation PON.

High-security multidimensional data protection system based on the Hartley algorithm-driven chaotic scheme.

This paper proposes a high-security multidimensional data protection system based on the Hartley algorithm-driven chaotic scheme. We utilize the fast Hartley algorithm instead of the fast fourier computation, and we employ chaotic sequences generated by the multi-winged chaotic system to achieve chaos-driven 3D constellation mapping, effectively integrating the chaotic system with the stochastic amplitude modulator. We reduce the signal's peak-to-average power ratio (PAPR) by deploying a random amplitude modulator. Simultaneously, this approach enhances the security of the physical layer of the signal. The PAPR reduction can reach up to 2.6 dB, while the most robust and stable modulator scheme can gain 2 dB. Finally, in the Hartley frequency domain, the signal's frequency is disrupted, providing the entire system with a key space of 10131 to resist violent cracking and thus improving the system's overall security. To validate the feasibility of our scheme in comparison to conventional IFFT-based encrypted 3D orthogonal frequency division multiplexing, We achieved a transmission rate of 27.94 Gb/s over a 2 km multicore fiber. Experimental results show that since the random amplitude generator effectively reduces PAPR, our proposed encryption scheme increases the forward error correction threshold range by 1.1 dB, verifying that our proposed scheme has highly reliable security performance.

Ultrahigh-order QAM secure transmission based on delta-sigma modulation using discrete memristive-enhanced chaos.

This Letter proposes a high-security and high-order signal transmission method that is based on delta-sigma modulation (DSM) and discrete memristive-enhanced chaos (DMEC). We employ the DMEC for the encryption of DSM signals to achieve a key space of 1098 in size. Moreover, we demonstrated a high-security transmission of 16384QAM signals using the DSM over a 25 km single-mode fiber in the intensity-modulated direct detection (IMDD) system. The experimental results show that the proposed ultrahigh-order transmission scheme based on DMEC and DSM guarantees high signal transmission performances with improved security and a key sensitivity level of 10-17.

Joint constellation shaping optical modulation scheme based on a pair of common-bottomed trigonal cones.

A joint constellation shaping (JCS) three-dimensional (3D) 16-ary modulation scheme constructed with a pair of common-bottomed trigonal cones (CBTC) as primitives is proposed. Compared to the 3D traditional constellation (TC) and the 3D geometric constellation shaping (GS) structure previously proposed by our group (GGS), the constellation figure of merit (CFM) is improved by 0.3906 and 0.0097, respectively. Meanwhile, probabilistic shaping (PS) is employed to optimize the 3D-CBTC-16CAP constellation structure for the second time to enhance the CFM of the constellation further. Compared to the 3D-CBTC-16CAP, after PS the 3D-JCS-16CAP has a CFM improvement of 0.5014. Experiments are carried out to transmit the signals across a 2 km seven-core fiber. At the bit error rate (BER) threshold ∼3.8 × 10-3, the 3D-CBTC-16CAP scheme demonstrates an improvement in the receiver sensitivity by 0.76 and 0.39 dB compared with 3D-TC-16CAP and 3D-GGS-16CAP. In addition, the transmission effect of the signals after joint PS is verified. Experiments show that the proposed 3D-JCS-16CAP scheme has the most significant enhancement effect when used in conjunction with PS, and the receiver sensitivity is improved by about 0.97 and 0.34 dB compared with the 3D-JTC-16CAP (3D-TC-16CAP signal after joint PS) and 3D-JGGS-16CAP (3D-GGS-16CAP signal after the joint PS).

Concurrent performance and security enhancement of ultrahigh-order DSM signals via null subcarriers.

In this paper, we propose leveraging null subcarriers in discrete multi-tone modulation (DMT) to process the DMT signal in both time and frequency domains. Additionally, we employ discrete memory enhanced chaos (DMEC) to scramble the signal in the frequency domain, thereby achieving physical layer signal encryption while ensuring a more uniform power distribution in the time-domain waveform. In our experimental demonstration, we achieved high-security transmission of a DSM-based 65536-QAM signal at a data rate of 16.01 Gb/s over a 25 km single-mode fiber (SMF) in an intensity-modulation direct-detection (IMDD) system. Additionally, in the transmission experiments for 13684-QAM and 65536-QAM signals, the proposed method demonstrated a receiver sensitivity gain of over 0.5 dB compared to the traditional DSM-based ultrahigh-order transmission.

Enhancing secure transmission and key distribution for ultrahigh-order QAM via delta-sigma modulation and discrete memristive-enhanced chaos.

In this Letter, we propose a method for ultrahigh-order QAM secure transmission and key distribution based on delta-sigma modulation (DSM) and discrete memristive-enhanced chaos (DMEC). The disturbance vectors generated by the DMEC scramble the DSM signals in both frequency and time domains, resulting in highly secure DSM signals. Through the key modulation and power adjustment and then superimposing them on the encrypted signals, the method achieves simultaneous transmission of keys and signals without the need for additional spectral resources. This approach allows for secure communication with continuous key iteration and updates, offering an effective solution for implementing "one-time pad" encryption. In the experimental demonstration, we achieved a secure transmission and key distribution of a 16384QAM signal at a rate of 17.09 Gb/s over 25 km in an intensity-modulated direct detection (IMDD) system, based on DSM.

Dynamic updated key distribution encryption scheme with the wireless rate of 102†Gb/s based on a syncretic W band-PON transmission system.

In this paper, a dynamic updated key distribution encryption scheme based on syncretic W band-passive optical network (PON) is proposed. The 102 Gb/s encrypted data rate using 64QAM is successfully transmitted over the 50 m wireless distance under 15% soft-decision forward error correction (SD-FEC) for a pre-FEC bit error rate (BER) threshold of 1.56 × 10-2. The scheme can realize an error-free public key transmission and public key updates up to 1014 times. In the encryption transmission system, there is a small deviation of the private key, and the received BER is more than 0.45. As far as we know, this is the first time to complete a dynamic key distribution based on a syncretic W band-PON system.

Sequence and epigenetic variations of R2R3-MYB transcription factors determine the diversity of taproot skin and flesh colors in different cultivated types of radish (Raphanus sativus L.).

KEY MESSAGE: This study found that three paralogous R2R3-MYB transcription factors exhibit functional divergence among different subspecies and cultivated types in radish. Cultivated radish taproots exhibit a wide range of color variations due to unique anthocyanin accumulation patterns in various tissues. This study investigated the universal principles of taproot color regulation that developed during domestication of different subspecies and cultivated types. The key candidate genes RsMYB1 and RsMYB2, which control anthocyanin accumulation in radish taproots, were identified using bulked segregant analysis in two genetic populations. We introduced the RsMYB1-RsF3'H-RsMYB1Met genetic model to elucidate the complex and unstable genetic regulation of taproot flesh color in Xinlimei radish. Furthermore, we analyzed the expression patterns of three R2R3-MYB transcription factors in lines with different taproot colors and investigated the relationship between RsMYB haplotypes and anthocyanin accumulation in a natural population of 56 germplasms. The results revealed that three paralogous RsMYBs underwent functional divergence during radish domestication, with RsMYB1 regulating the red flesh of Xinlimei radish, and RsMYB2 and RsMYB3 regulating the red skin of East Asian big long radish (R. sativus var. hortensis) and European small radish (R. sativus var. sativus), respectively. Moreover, RsMYB1-H1, RsMYB2-H10, and RsMYB3-H6 were identified as the primary haplotypes exerting regulatory functions on anthocyanin synthesis. These findings provide an understanding of the genetic mechanisms regulating anthocyanin synthesis in radish and offer a potential strategy for early prediction of color variations in breeding programs.

Solvent-induced dual nucleophiles and the α-effect in the SN2 versus E2 competition.

We have quantum chemically investigated how microsolvation affects the various E2 and SN2 pathways, their mutual competition, and the α-effect of the model reaction system HOO-(H2O)n + CH3CH2Cl, at the CCSD(T) level. Interestingly, we identify the dual nature of the α-nucleophile HOO- which, upon solvation, is in equilibrium with HO-. This solvent-induced dual appearance gives rise to a rich network of competing reaction channels. Among both nucleophiles, SN2 is always favored over E2, and this preference increases upon increasing microsolvation. Furthermore, we found a pronounced α-effect, not only for SN2 substitution but also for E2 elimination, i.e., HOO- is more reactive than HO- in both cases. Our activation strain and quantitative molecular orbital analyses reveal the physical mechanisms behind the various computed trends. In particular, we demonstrate that two recently proposed criteria, required for solvent-free nucleophiles to display the α-effect, must also be satisfied by microsolvated HOO-(H2O)n nucleophiles.

Shapeshifting Nucleophiles HO-(NH3)n React with Methyl Chloride.

The microsolvated anions HO-(NH3)n were found to induce new nucleophile NH2-(H2O)(NH3)n-1 via intramolecular proton transfer. Hence, the ion-molecule nucleophilic substitution (SN2) reaction between CH3Cl and these shapeshifting nucleophiles lead to both the HO- path and NH2- path, meaning that the respective attacking nucleophile is HO- or NH2-. The CCSD(T) level of calculation was performed to characterize the potential energy surfaces. Calculations indicate that the HO- species are lower in energy than the NH2- species, and the SN2 reaction barriers are lower for the HO- path than the NH2--path. Incremental solvation increases the barrier for both paths. Comparison between HO-(NH3)n and HOO-(NH3)n confirmed the existence of an α-effect under microsolvated conditions. Comparison between HO-(NH3)n and HO-(H2O)n indicated that the more polarized H2O stabilizes the nucleophiles more than NH3, and thus, the hydrated systems have higher SN2 reaction barriers. The aforementioned barrier changes can be explained by the differential stabilization of the nucleophile and HOMO levels upon solvation, thus affecting the HOMO-LUMO interaction between the nucleophile and substrate. For the same kind of nucleophilic attacking atom, O or N, the reaction barrier has a good linear correlation with the HOMO level of the nucleophiles. Hence, the HOMO level or the binding energy of microsolvated nucleophiles is a good indicator to evaluate the order of barrier heights. This work expands our understanding of the microsolvation effect on prototype SN2 reactions beyond the water solvent.

Shapeshifting Nucleophile Singly Hydrated Hydroperoxide Anion Leads to the Occurrence of the Thermodynamically Unfavored SN2 Product.

Single water molecules alone may introduce unusual features into the kinetics and dynamics of chemical reactions. The singly hydrated hydroperoxide anion, HOO-(H2O), was found to be a shapeshifting nucleophile, which can be transformed to HO- solvated by hydrogen peroxide HO-(HOOH). Herein, we performed direct dynamics simulations of its reaction with methyl iodide to investigate the effect of individual water molecules. In addition to the normal SN2 product CH3OOH, the thermodynamically unfavored proton transfer-induced HO--SN2 path (produces CH3OH) was also observed, contributing ∼4%. The simulated branching ratio of the HO--SN2 path exceeded the statistical estimation (0.6%) based on the free energy barrier difference. The occurrence of the HO--SN2 path was attributed to the shallow entrance channel well before a submerged saddle point, thus providing a region for extensive proton exchange and ultimately leading to the formation of CH3OH. In comparison, changing the leaving group from Cl to I increased the overall reaction rate as well as the proportion of the HO--SN2 path because the CH3I system has a smaller internal barrier. This work elucidates the importance of the dynamic effect introduced by a single solvent molecule to alter the product channel and kinetics of typical ion-molecule SN2 reactions.

Apoptotic vesicles (apoVs) derived from fibroblast-converted hepatocyte-like cells effectively ameliorate liver fibrosis.

Liver fibrosis is a serious global health issue for which effective treatment remains elusive. Chemical-induced hepatocyte-like cells (ciHeps) have emerged as an appealing source for cell transplantation therapy, although they present several challenges such as the risk of lung thromboembolism or hemorrhage. Apoptotic vesicles (apoVs), small membrane vesicles generated during the apoptosis process, have gained attention for their role in regulating various physiological and pathological processes. In this study, we generated ciHep-derived apoVs (ciHep-apoVs) and investigated their therapeutic potential in alleviating liver fibrosis. Our findings revealed that ciHep-apoVs induced the transformation of macrophages into an anti-inflammatory phenotype, effectively suppressed the activity of activated hepatic stellate cells (aHSCs), and enhanced the survival of hepatocytes. When intravenously administered to mice with liver fibrosis, ciHep-apoVs were primarily engulfed by macrophages and myofibroblasts, leading to a reduction in liver inflammation and fibrosis. Proteomic and miRNA analyses showed that ciHep-apoVs were enriched in various functional molecules that modulate crucial cellular processes, including metabolism, signaling transduction, and ECM-receptor interactions. ciHep-apoVs effectively suppressed aHSCs activity through the synergistic inhibition of glycolysis, the PI3K/AKT/mTOR pathway, and epithelial-to-mesenchymal transition (EMT) cascades. These findings highlight the potential of ciHep-apoVs as multifunctional nanotherapeutics for liver fibrosis and provide insights into the treatment of other liver diseases and fibrosis in other organs.

Transcription-coupled donor DNA expression increases homologous recombination for efficient genome editing.

Genomes can be edited by homologous recombination stimulated by CRISPR/Cas9 [clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated peptide 9]-induced DNA double-strand breaks. However, this approach is inefficient for inserting or deleting long fragments in mammalian cells. Here, we describe a simple genome-editing method, termed transcription-coupled Cas9-mediated editing (TEd), that can achieve higher efficiencies than canonical Cas9-mediated editing (CEd) in deleting genomic fragments, inserting/replacing large DNA fragments and introducing point mutations into mammalian cell lines. We also found that the transcription on DNA templates is crucial for the promotion of homology-directed repair, and that tethering transcripts from TEd donors to targeted sites further improves editing efficiency. The superior efficiency of TEd for the insertion and deletion of long DNA fragments expands the applications of CRISPR for editing mammalian genomes.